Science.gov

Sample records for activity significantly reduced

  1. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  2. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  3. Significantly reduced cytochrome P450 3A4 expression and activity in liver from humans with diabetes mellitus

    PubMed Central

    Dostalek, Miroslav; Court, Michael H; Yan, Bingfang; Akhlaghi, Fatemeh

    2011-01-01

    BACKGROUND AND PURPOSE Patients with diabetes mellitus require pharmacotherapy with numerous medications. However, the effect of diabetes on drug biotransformation is not well understood. Our goal was to investigate the effect of diabetes on liver cytochrome P450 3As, the most abundant phase I drug-metabolizing enzymes in humans. EXPERIMENTAL APPROACH Human liver microsomal fractions (HLMs) were prepared from diabetic (n = 12) and demographically matched nondiabetic (n = 12) donors, genotyped for CYP3A4*1B and CYP3A5*3 polymorphisms. Cytochrome P450 3A4, 3A5 and 2E1 mRNA expression, protein level and enzymatic activity were compared between the two groups. KEY RESULTS Midazolam 1′- or 4-hydroxylation and testosterone 6β-hydroxylation, catalyzed by P450 3A, were markedly reduced in diabetic HLMs, irrespective of genotype. Significantly lower P450 3A4 protein and comparable mRNA levels were observed in diabetic HLMs. In contrast, neither P450 3A5 protein level nor mRNA expression differed significantly between the two groups. Concurrently, we have observed increased P450 2E1 protein level and higher chlorzoxazone 6-hydroxylation activity in diabetic HLMs. CONCLUSIONS AND IMPLICATIONS These studies indicate that diabetes is associated with a significant decrease in hepatic P450 3A4 enzymatic activity and protein level. This finding could be clinically relevant for diabetic patients who have additional comorbidities and are receiving multiple medications. To further characterize the effect of diabetes on P450 3A4 activity, a well-controlled clinical study in diabetic patients is warranted. PMID:21323901

  4. Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury

    PubMed Central

    Faridi, Mohd Hafeez; Altintas, Mehmet M.; Gomez, Camilo; Duque, Juan Camilo; Vazquez-Padron, Roberto I.; Gupta, Vineet

    2013-01-01

    BACKGROUND CD11b/CD18 is a key adhesion receptor that mediates leukocyte adhesion, migration and immune functions. We recently identified novel compounds, leukadherins, that allosterically enhance CD11b/CD18-dependent cell adhesion and reduce inflammation in vivo, suggesting integrin activation to be a novel mechanism of action for the development of anti-inflammatory therapeutics. Since a number of well-characterized anti-CD11b/CD18 activating antibodies are currently available, we wondered if such biological agonists could also become therapeutic leads following this mechanism of action. METHODS We compared the two types of agonists using in vitro cell adhesion and wound-healing assays and using animal model systems. We also studied effects of the two types of agonists on outside-in signaling in treated cells. RESULTS Both types of agonists similarly enhanced integrin-mediated cell adhesion and decreased cell migration. However, unlike leukadherins, the activating antibodies produced significant CD11b/CD18 macro clustering and induced phosphorylation of key proteins involved in outside-in signaling. Studies using conformation reporter antibodies showed that leukadherins did not induce global conformational changes in CD11b/CD18 explaining the reason behind their lack of ligand-mimetic outside-in signaling. In vivo, leukadherins reduced vascular injury in a dose-dependent fashion, but, surprisingly, the anti-CD11b activating antibody ED7 was ineffective. CONCLUSIONS Our results suggest that small molecule allosteric agonists of CD11b/CD18 have clear advantages over the biologic activating antibodies and provide a mechanistic basis for the difference. GENERAL SIGNIFICANCE CD11b/CD18 activation represents a novel strategy for reducing inflammatory injury. Our study establishes small molecule leukadherins as preferred agonists over activating antibodies for future development as novel anti-inflammatory therapeutics. PMID:23454649

  5. Triple drug immunosuppression significantly reduces immune activation and allograft arteriosclerosis in cytomegalovirus-infected rat aortic allografts and induces early latency of viral infection.

    PubMed Central

    Lemström, K. B.; Bruning, J. H.; Bruggeman, C. A.; Lautenschlager, I. T.; Häyry, P. J.

    1994-01-01

    The effect of triple drug immunosuppression (cyclosporine A 10 mg/kg/day+methylprednisolone 0.5 mg/kg/day+azathioprine 2 mg/kg/day) on rat cytomegalovirus (RCMV)-enhanced allograft arteriosclerosis was investigated applying WF (AG-B2, RT1v) recipients of DA (AG-B4, RT1a) aortic allografts. The recipients were inoculated intraperitoneally with 10(5) plaque-forming units of RCMV 1 day after transplantation or left noninfected. The grafts were removed on 7 and 14 days, and at 1, 3, and 6 months after transplantation. The presence of viral infection was demonstrated by plaque assays, cell proliferation by [3H]thymidine autoradiography, and vascular wall alterations by quantitative histology and immunohistochemistry. Triple drug immunosuppression reduced the presence of infectious virus in plaque assays and induced early latency of viral infection. It significantly reduced the peak adventitial inflammatory response (P < 0.05) and reduced and delayed intimal nuclear intensity and intimal thickening (P < 0.05) in RCMV-infected allografts. The proliferative response of smooth muscle cells was reduced by triple drug immunosuppression to 50% of that observed in nonimmunosuppressed RCMV-infected allografts, but still the proliferative peak response was seen at 1 month. Only low level immune activation, ie, the expression of interleukin-2 receptor (P < 0.05) and MHC class II, was observed under triple drug immunosuppression in the adventitia of RCMV-infected allografts, whereas there was no substantial change in the phenotypic distribution of inflammatory cells. In conclusion, although RCMV infection significantly enhances allograft arteriosclerosis also in immunosuppressed allografts, triple drug immunosuppression has no additional detrimental effect but rather a protective one on vascular wall histology. These results further suggest that RCMV-enhanced allograft arteriosclerosis may be an immunopathological condition linked to the host immune response toward the graft and

  6. Pyrolysis of wastewater biosolids significantly reduces estrogenicity.

    PubMed

    Hoffman, T C; Zitomer, D H; McNamara, P J

    2016-11-01

    Most wastewater treatment processes are not specifically designed to remove micropollutants. Many micropollutants are hydrophobic so they remain in the biosolids and are discharged to the environment through land-application of biosolids. Micropollutants encompass a broad range of organic chemicals, including estrogenic compounds (natural and synthetic) that reside in the environment, a.k.a. environmental estrogens. Public concern over land application of biosolids stemming from the occurrence of micropollutants hampers the value of biosolids which are important to wastewater treatment plants as a valuable by-product. This research evaluated pyrolysis, the partial decomposition of organic material in an oxygen-deprived system under high temperatures, as a biosolids treatment process that could remove estrogenic compounds from solids while producing a less hormonally active biochar for soil amendment. The estrogenicity, measured in estradiol equivalents (EEQ) by the yeast estrogen screen (YES) assay, of pyrolyzed biosolids was compared to primary and anaerobically digested biosolids. The estrogenic responses from primary solids and anaerobically digested solids were not statistically significantly different, but pyrolysis of anaerobically digested solids resulted in a significant reduction in EEQ; increasing pyrolysis temperature from 100°C to 500°C increased the removal of EEQ with greater than 95% removal occurring at or above 400°C. This research demonstrates that biosolids treatment with pyrolysis would substantially decrease (removal>95%) the estrogens associated with this biosolids product. Thus, pyrolysis of biosolids can be used to produce a valuable soil amendment product, biochar, that minimizes discharge of estrogens to the environment. PMID:27344259

  7. Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

    PubMed Central

    Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

    2012-01-01

    Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; P<0.05; n=10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

  8. Reducing Human-Tsetse Contact Significantly Enhances the Efficacy of Sleeping Sickness Active Screening Campaigns: A Promising Result in the Context of Elimination

    PubMed Central

    Courtin, Fabrice; Camara, Mamadou; Rayaisse, Jean-Baptiste; Kagbadouno, Moise; Dama, Emilie; Camara, Oumou; Traoré, Ibrahima S.; Rouamba, Jérémi; Peylhard, Moana; Somda, Martin B.; Leno, Mamadou; Lehane, Mike J.; Torr, Steve J.; Solano, Philippe; Jamonneau, Vincent; Bucheton, Bruno

    2015-01-01

    Background Control of gambiense sleeping sickness, a neglected tropical disease targeted for elimination by 2020, relies mainly on mass screening of populations at risk and treatment of cases. This strategy is however challenged by the existence of undetected reservoirs of parasites that contribute to the maintenance of transmission. In this study, performed in the Boffa disease focus of Guinea, we evaluated the value of adding vector control to medical surveys and measured its impact on disease burden. Methods The focus was divided into two parts (screen and treat in the western part; screen and treat plus vector control in the eastern part) separated by the Rio Pongo river. Population census and baseline entomological data were collected from the entire focus at the beginning of the study and insecticide impregnated targets were deployed on the eastern bank only. Medical surveys were performed in both areas in 2012 and 2013. Findings In the vector control area, there was an 80% decrease in tsetse density, resulting in a significant decrease of human tsetse contacts, and a decrease of disease prevalence (from 0.3% to 0.1%; p=0.01), and an almost nil incidence of new infections (<0.1%). In contrast, incidence was 10 times higher in the area without vector control (>1%, p<0.0001) with a disease prevalence increasing slightly (from 0.5 to 0.7%, p=0.34). Interpretation Combining medical and vector control was decisive in reducing T. b. gambiense transmission and in speeding up progress towards elimination. Similar strategies could be applied in other foci. PMID:26267667

  9. Bacteriophage cocktail significantly reduces Escherichia coli O157

    PubMed Central

    Carter, Chandi D.; Parks, Adam; Abuladze, Tamar; Li, Manrong; Woolston, Joelle; Magnone, Joshua; Senecal, Andre; Kropinski, Andrew M.; Sulakvelidze, Alexander

    2012-01-01

    Foods contaminated with Escherichia coli O157:H7 cause more than 63,000 foodborne illnesses in the United States every year, resulting in a significant economic impact on medical costs and product liabilities. Efforts to reduce contamination with E. coli O157:H7 have largely focused on washing, application of various antibacterial chemicals, and gamma-irradiation, each of which has practical and environmental drawbacks. A relatively recent, environmentally-friendly approach proposed for eliminating or significantly reducing E. coli O157:H7 contamination of foods is the use of lytic bacteriophages as biocontrol agents. We found that EcoShield™, a commercially available preparation composed of three lytic bacteriophages specific for E. coli O157:H7, significantly (p < 0.05) reduced the levels of the bacterium in experimentally contaminated beef by ≥ 94% and in lettuce by 87% after a five minute contact time. The reduced levels of bacteria were maintained for at least one week at refrigerated temperatures. However, the one-time application of EcoShield™ did not protect the foods from recontamination with E. coli O157:H7. Our results demonstrate that EcoShield™ is effective in significantly reducing contamination of beef and lettuce with E. coli O157:H7, but does not protect against potential later contamination due to, for example, unsanitary handling of the foods post processing. PMID:23275869

  10. Diagnostic Significance of Reduced IgA in Children

    PubMed Central

    Nurkic, Jasmina; Numanovic, Fatima; Arnautalic, Lejla; Tihic, Nijaz; Halilovic, Dzenan; Jahic, Mahira

    2015-01-01

    Introduction: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In older children decreased IgA may lead to serious illnesses that need to be recognize and acknowledge through the appropriate diagnostic methods. At the University Clinical Center Tuzla, children with suspected deficient immune response due to reduced values of IgA, goes through further diagnostic evaluation at the Polyclinic for Laboratory Medicine, Department of Immunology and Department of Microbiology, as well as the Clinic of Radiology. Material and methods: Our study followed 91 patients, for the year 2013, through their medical charts and made evaluation of diagnostic and screening tests. Conclusion: The significance of this paper is to draw attention to the importance of diagnostic approach to IgA deficient pediatric patient and relevance of knowledge of individual diagnostic methods as well as to the proper interpretation of the results thereof. PMID:26543309

  11. Cytochrome bd Displays Significant Quinol Peroxidase Activity

    PubMed Central

    Al-Attar, Sinan; Yu, Yuanjie; Pinkse, Martijn; Hoeser, Jo; Friedrich, Thorsten; Bald, Dirk; de Vries, Simon

    2016-01-01

    Cytochrome bd is a prokaryotic terminal oxidase that catalyses the electrogenic reduction of oxygen to water using ubiquinol as electron donor. Cytochrome bd is a tri-haem integral membrane enzyme carrying a low-spin haem b558, and two high-spin haems: b595 and d. Here we show that besides its oxidase activity, cytochrome bd from Escherichia coli is a genuine quinol peroxidase (QPO) that reduces hydrogen peroxide to water. The highly active and pure enzyme preparation used in this study did not display the catalase activity recently reported for E. coli cytochrome bd. To our knowledge, cytochrome bd is the first membrane-bound quinol peroxidase detected in E. coli. The observation that cytochrome bd is a quinol peroxidase, can provide a biochemical basis for its role in detoxification of hydrogen peroxide and may explain the frequent findings reported in the literature that indicate increased sensitivity to hydrogen peroxide and decreased virulence in mutants that lack the enzyme. PMID:27279363

  12. The significance of sensory appeal for reduced meat consumption.

    PubMed

    Tucker, Corrina A

    2014-10-01

    Reducing meat (over-)consumption as a way to help address environmental deterioration will require a range of strategies, and any such strategies will benefit from understanding how individuals might respond to various meat consumption practices. To investigate how New Zealanders perceive such a range of practices, in this instance in vitro meat, eating nose-to-tail, entomophagy and reducing meat consumption, focus groups involving a total of 69 participants were held around the country. While it is the damaging environmental implications of intensive farming practices and the projected continuation of increasing global consumer demand for meat products that has propelled this research, when asked to consider variations on the conventional meat-centric diet common to many New Zealanders, it was the sensory appeal of the areas considered that was deemed most problematic. While an ecological rationale for considering these 'meat' alternatives was recognised and considered important by most, transforming this value into action looks far less promising given the recurrent sensory objections to consuming different protein-based foods or of reducing meat consumption. This article considers the responses of focus group participants in relation to each of the dietary practices outlined, and offers suggestions on ways to encourage a more environmentally viable diet. PMID:24953197

  13. Bacteriophage significantly reduces Listeria monocytogenes on raw salmon fillet tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have demonstrated the antilisterial activity of generally recognized as safe (GRAS) bacteriophage LISTEX P100 (phage P100) on the surface of raw salmon fillet tissue against Listeria monocytogenes serotypes 1/2a and 4b. In a broth model system, phage P100 completely inhibited L. monocytogenes gro...

  14. Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

    PubMed Central

    Kayiran, Oguz; Cuzdan, Suat S.; Uysal, Afsin; Kocer, Ugur

    2013-01-01

    Introduction: Numerous pharmacological agents have been used to enhance the viability of flaps. Ischemia reperfusion (I/R) injury is an unwanted, sometimes devastating complication in reconstructive microsurgery. Tadalafil, a specific inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction, and acts on vascular smooth muscles, platelets and leukocytes. Herein, the protective and therapeutical effect of tadalafil in I/R injury in rat skin flap model is evaluated. Materials and Methods: Sixty epigastric island flaps were used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group, medication group). Biochemical markers including total nitrite, malondialdehyde (MDA) and myeloperoxidase (MPO) were analysed. Necrosis rates were calculated and histopathologic evaluation was carried out. Results: MDA, MPO and total nitrite values were found elevated in the ischemic group, however there was an evident drop in the medication group. Histological results revealed that early inflammatory findings (oedema, neutrophil infiltration, necrosis rate) were observed lower with tadalafil administration. Moreover, statistical significance (P < 0.05) was recorded. Conclusions: We conclude that tadalafil has beneficial effects on epigastric island flaps against I/R injury. PMID:23960309

  15. Significant Quantum Effects in Hydrogen Activation

    SciTech Connect

    Kyriakou, Georgios; Davidson, Erlend R.; Peng, Guowen; Roling, Luke T.; Singh, Suyash; Boucher, Matthew B.; Marcinkowski, Matthew D.; Mavrikakis, Manos; Michaelides, Angelos; Sykes, E. Charles H.

    2014-03-31

    Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to 190 K and for D2 up to 140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation.

  16. Significant Quantum Effects in Hydrogen Activation

    PubMed Central

    2014-01-01

    Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to ∼190 K and for D2 up to ∼140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation. PMID:24684530

  17. Active structures to reduce torsional vibrations

    NASA Astrophysics Data System (ADS)

    Matthias, M.; Schlote, D.; Atzrodt, H.

    2013-03-01

    This paper describes the development of different active measures to reduce torsional vibrations in power trains. The measures are based on concepts developed for active mounts to reduce the transmission of structure-borne sound. To show the potential of these active measures and investigate their mode of operation to influence torsional vibrations, numerical simulations of powertrains with different active measures were done. First experimental results from tests on an experimental (reduced size) power train were used to align the numerical models. The work was done within the project 'LOEWE-Zentrum AdRIA: Adaptronik - Research, Innovation, Application' funded by the German federal state of Hessen, and the Project AKTos: 'Active control of torsional vibrations by coupling elements' placed in the research Framework program 'Navigation and Maritime Technology for the 21st Century' funded by the German Federal Ministry of Economics and Technology.

  18. Methylphenidate significantly reduces lapses of attention during on-road highway driving in patients with ADHD.

    PubMed

    Verster, Joris C; Roth, Thomas

    2014-10-01

    Lapses of attention are characteristic for attention-deficit/hyperactivity disorder (ADHD) and as such may impair performance of daily activities. Data from an on-road driving study were reanalyzed to determine lapses in patients with ADHD after treatment with methylphenidate and placebo.A total of 18 adult ADHD patients performed a 100-km on-road driving test and were instructed to drive with a steady lateral position and constant speed. The SD of lateral position (SDLP), that is, the weaving of the car, lapses, and alertness, was assessed.Driving was significantly better (P = 0.006) with methylphenidate (SDLP, 18.8 cm) when compared with placebo (SDLP, 21.2 cm). Both the reduction in SDLP and the number of lapses (P = 0.003) confirm this significant improvement, which is further supported by subjective assessments of perceived driving performance. Although lapses were common in the placebo condition (11/18 patients), they were much less frequently observed (5/18 patients) after treatment with methylphenidate. Postdriving assessments suggest that lapses often go unnoticed by drivers.In conclusion, methylphenidate significantly improves driving of patients with ADHD by significantly reducing the number of lapses. PMID:24978156

  19. Cardiovascular function following reduced aerobic activity

    NASA Technical Reports Server (NTRS)

    Raven, P. B.; Welch-O'Connor, R. M.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure

  20. Reducing Skin Picking via Competing Activities

    ERIC Educational Resources Information Center

    Lane, Kathleen Lynne; Thompson, Ada; Reske, Cara L.; Gable, Lauren M.; Barton-Arwood, Sally

    2006-01-01

    This study examined the outcomes of a competing activities intervention to decrease skin picking exhibited by a 9-year-old student with comorbid diagnoses. Results of an ABCBAB design revealed that the use of student-selected manipulatives resulted in reduced skin picking. (Contains 1 figure.)

  1. Utilization of UV Curing Technology to Significantly Reduce the Manufacturing Cost of LIB Electrodes

    SciTech Connect

    Voelker, Gary; Arnold, John

    2015-11-30

    Previously identified novel binders and associated UV curing technology have been shown to reduce the time required to apply and finish electrode coatings from tens of minutes to less than one second. This revolutionary approach can result in dramatic increases in process speeds, significantly reduced capital (a factor of 10 to 20) and operating costs, reduced energy requirements, and reduced environmental concerns and costs due to the virtual elimination of harmful volatile organic solvents and associated solvent dryers and recovery systems. The accumulated advantages of higher speed, lower capital and operating costs, reduced footprint, lack of VOC recovery, and reduced energy cost is a reduction of 90% in the manufacturing cost of cathodes. When commercialized, the resulting cost reduction in Lithium batteries will allow storage device manufacturers to expand their sales in the market and thereby accrue the energy savings of broader utilization of HEVs, PHEVs and EVs in the U.S., and a broad technology export market is also envisioned.

  2. Study examines sulfate-reducing bacteria activity

    SciTech Connect

    McElhiney, J.E.; Hardy, J.A.; Rizk, T.Y.; Stott, J.F.D.; Eden, R.D.

    1996-12-09

    Low-sulfate seawater injection can reduce the potential of an oil reservoir turning sour because of sulfate-reducing bacteria. Sulfate-reducing bacteria (SRB) convert sulfate ions in seawater used in waterflooding into sulfide with the concomitant oxidation of a carbon source. A recent study at Capcis investigated the efficiency of SRB under various conditions of sulfate limitation. This study was conducted in a flowing bioreactor at 2,000 psia with different temperature zones (mesophilic 35 C and thermophilic 60--80 C). The study mixed microfloral populations derived from real North Sea-produced fluids, and included an active population of marine methanogenic bacteria present to provide competition for the available carbon sources. In general, results showed that SRB continue to convert sulfate to sulfide in stoichiometric quantities without regard to absolute concentrations. The paper discusses the results and recommends nanofiltration of seawater for ``sweet`` reservoirs.

  3. Infliximab treatment reduces complement activation in patients with rheumatoid arthritis

    PubMed Central

    Familian, A; Voskuyl, A; van Mierlo, G J; Heijst, H; Twisk, J; Dijkmans, B; Hack, C

    2005-01-01

    Background: Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA. Objective: To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA. Methods: 35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time. Results: At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment. Conclusion: Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA. PMID:15958758

  4. Systematic review of active workplace interventions to reduce sickness absence

    PubMed Central

    2013-01-01

    Background The workplace is used as a setting for interventions to prevent and reduce sickness absence, regardless of the specific medical conditions and diagnoses. Aims To give an overview of the general effectiveness of active workplace interventions aimed at preventing and reducing sickness absence. Methods We systematically searched PubMed, Embase, Psych-info, and ISI web of knowledge on 27 December 2011. Inclusion criteria were (i) participants over 18 years old with an active role in the intervention, (ii) intervention done partly or fully at the workplace or at the initiative of the workplace and (iii) sickness absence reported. Two reviewers independently screened articles, extracted data and assessed risk of bias. A narrative synthesis was used. Results We identified 2036 articles of which, 93 were assessed in full text. Seventeen articles were included (2 with low and 15 with medium risk of bias), with a total of 24 comparisons. Five interventions from four articles significantly reduced sickness absence. We found moderate evidence that graded activity reduced sickness absence and limited evidence that the Sheerbrooke model (a comprehensive multidisciplinary intervention) and cognitive behavioural therapy (CBT) reduced sickness absence. There was moderate evidence that workplace education and physical exercise did not reduce sickness absence. For other interventions, the evidence was insufficient to draw conclusions. Conclusions The review found limited evidence that active workplace interventions were not generally effective in reducing sickness absence, but there was moderate evidence of effect for graded activity and limited evidence for the effectiveness of the Sheerbrooke model and CBT. PMID:23223750

  5. Stimuli Reduce the Dimensionality of Cortical Activity.

    PubMed

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    2016-01-01

    The activity of ensembles of simultaneously recorded neurons can be represented as a set of points in the space of firing rates. Even though the dimension of this space is equal to the ensemble size, neural activity can be effectively localized on smaller subspaces. The dimensionality of the neural space is an important determinant of the computational tasks supported by the neural activity. Here, we investigate the dimensionality of neural ensembles from the sensory cortex of alert rats during periods of ongoing (inter-trial) and stimulus-evoked activity. We find that dimensionality grows linearly with ensemble size, and grows significantly faster during ongoing activity compared to evoked activity. We explain these results using a spiking network model based on a clustered architecture. The model captures the difference in growth rate between ongoing and evoked activity and predicts a characteristic scaling with ensemble size that could be tested in high-density multi-electrode recordings. Moreover, we present a simple theory that predicts the existence of an upper bound on dimensionality. This upper bound is inversely proportional to the amount of pair-wise correlations and, compared to a homogeneous network without clusters, it is larger by a factor equal to the number of clusters. The empirical estimation of such bounds depends on the number and duration of trials and is well predicted by the theory. Together, these results provide a framework to analyze neural dimensionality in alert animals, its behavior under stimulus presentation, and its theoretical dependence on ensemble size, number of clusters, and correlations in spiking network models. PMID:26924968

  6. Stimuli Reduce the Dimensionality of Cortical Activity

    PubMed Central

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    2016-01-01

    The activity of ensembles of simultaneously recorded neurons can be represented as a set of points in the space of firing rates. Even though the dimension of this space is equal to the ensemble size, neural activity can be effectively localized on smaller subspaces. The dimensionality of the neural space is an important determinant of the computational tasks supported by the neural activity. Here, we investigate the dimensionality of neural ensembles from the sensory cortex of alert rats during periods of ongoing (inter-trial) and stimulus-evoked activity. We find that dimensionality grows linearly with ensemble size, and grows significantly faster during ongoing activity compared to evoked activity. We explain these results using a spiking network model based on a clustered architecture. The model captures the difference in growth rate between ongoing and evoked activity and predicts a characteristic scaling with ensemble size that could be tested in high-density multi-electrode recordings. Moreover, we present a simple theory that predicts the existence of an upper bound on dimensionality. This upper bound is inversely proportional to the amount of pair-wise correlations and, compared to a homogeneous network without clusters, it is larger by a factor equal to the number of clusters. The empirical estimation of such bounds depends on the number and duration of trials and is well predicted by the theory. Together, these results provide a framework to analyze neural dimensionality in alert animals, its behavior under stimulus presentation, and its theoretical dependence on ensemble size, number of clusters, and correlations in spiking network models. PMID:26924968

  7. Aerodynamic Improvements of an Empty Timber Truck can Have the Potential of Significantly Reducing Fuel Consumption

    NASA Astrophysics Data System (ADS)

    Andersson, Magnus; Marashi, Seyedeh Sepideh; Karlsson, Matts

    2012-11-01

    In the present study, aerodynamic drag (AD) has been estimated for an empty and a fully loaded conceptual timber truck (TT) using Computational Fluid Dynamics (CFD). The increasing fuel prices have challenged heavy duty vehicle (HDV) manufactures to strive for better fuel economy, by e.g. utilizing drag reducing external devices. Despite this knowledge, the TT fleets seem to be left in the dark. Like HDV aerodynamics, similarities can be observed as a large low pressure wake is formed behind the tractor (unloaded) and downstream of the trailer (full load) thus generating AD. As TTs travel half the time without any cargo, focus on drag reduction is important. The full scaled TTs where simulated using the realizable k-epsilon model with grid adaption techniques for mesh independence. Our results indicate that a loaded TT reduces the AD significantly as both wake size and turbulence kinetic energy are lowered. In contrast to HDV the unloaded TTs have a much larger design space available for possible drag reducing devices, e.g. plastic wrapping and/or flaps. This conceptual CFD study has given an indication of the large AD difference between the unloaded and fully loaded TT, showing the potential for significant AD improvements.

  8. Significantly reduced expression of the proteoglycan decorin in Alzheimer's disease fibroblasts

    PubMed Central

    Brandan, Enrique; Melo, Francisco; García, María; Contreras, Maribel

    1996-01-01

    Aims—To investigate whether proteoglycan synthesis is altered in skin fibroblasts in patients with Alzheimer's disease compared with normal subjects. Methods—Cell lines obtained from donors with Alzheimer's disease and healthy controls were incubated with radioactive sulphate. The proteoglycans synthesised were determined and analysed by chromatographic, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and glycosaminoglycans-lyase treatment. The amount of decorin synthesised by each cell line was quantified using western blot analysis. Transcripts for human decorin were determined using northern blot analysis. Results—No significant changes in total sulphate incorporation and glycos-aminoglycan (GAG) composition were detected in the incubation media of these cells. However, chromatographic and SDS-PAGE analysis of the proteoglycans secreted by the cell lines showed that a dermatan sulphate proteoglycan of 150-125 kilodaltons was substantially reduced in Alzheimer's disease fibroblasts. The molecular characteristics of this proteoglycan correspond to decorin. Western blot analysis indicated that decorin was reduced in Alzheimer's disease incubation medium compared with normal medium. Northern blotting indicated that in Alzheimer's disease fibroblasts decorin transcripts were significantly reduced compared with normal fibroblasts. Glypican concentrations, a cell surface heparan sulphate proteoglycan, remained the same. Conclusions—These results strongly suggest that the expression and synthesis of decorin is affected in Alzheimer's disease skin fibroblasts. Images PMID:16696102

  9. Multiwalled Carbon Nanotube Functionalization with High Molecular Weight Hyaluronan Significantly Reduces Pulmonary Injury.

    PubMed

    Hussain, Salik; Ji, Zhaoxia; Taylor, Alexia J; DeGraff, Laura M; George, Margaret; Tucker, Charles J; Chang, Chong Hyun; Li, Ruibin; Bonner, James C; Garantziotis, Stavros

    2016-08-23

    Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs. Using in vivo and in vitro approaches, we investigated the effectiveness of MWCNT functionalization with HA in increasing nanotube biocompatibility and reducing lung inflammatory and fibrotic effects. We utilized three-dimensional cultures of differentiated primary human bronchial epithelia to translate findings from rodent assays to humans. We found that HA functionalization increased stability and dispersion of MWCNTs and reduced postexposure lung inflammation, fibrosis, and mucus cell metaplasia compared with nonfunctionalized MWCNTs. Cocultures of fully differentiated bronchial epithelial cells (cultivated at air-liquid interface) and human lung fibroblasts (submerged) displayed significant reduction in injury, oxidative stress, as well as pro-inflammatory gene and protein expression after exposure to HA-functionalized MWCNTs compared with MWCNTs alone. In contrast, neither type of nanotubes stimulated cytokine production in primary human alveolar macrophages. In aggregate, our results demonstrate the effectiveness of HA functionalization as a safer design approach to eliminate MWCNT-induced lung injury and suggest that HA functionalization works by reducing MWCNT-induced epithelial injury. PMID:27459049

  10. A Chimpanzee Recognizes Synthetic Speech With Significantly Reduced Acoustic Cues to Phonetic Content

    PubMed Central

    Heimbauer, Lisa A.; Beran, Michael J.; Owren, Michael J.

    2011-01-01

    Summary A long-standing debate concerns whether humans are specialized for speech perception [1–7], which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content [2–4,7]. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words [8,9], asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuo-graphic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users [10]. Experiment 2 tested “impossibly unspeechlike” [3] sine-wave (SW) synthesis, which reduces speech to just three moving tones [11]. Although receiving only intermittent and non-contingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate, but improved in Experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human [12–14]. PMID:21723125

  11. Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis.

    PubMed

    Neu, Alicia M; Richardson, Troy; Lawlor, John; Stuart, Jayne; Newland, Jason; McAfee, Nancy; Warady, Bradley A

    2016-06-01

    The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates. PMID:27165827

  12. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... amendments significantly reducing the rate of future benefit accrual. 54.4980F-1 Section 54.4980F-1 Internal... significantly reducing the rate of future benefit accrual. The following questions and answers concern the... a plan amendment of an applicable pension plan that significantly reduces the rate of future...

  13. Significantly reduced radiation dose to operators during percutaneous vertebroplasty using a new cement delivery device

    PubMed Central

    2014-01-01

    Background Percutaneous vertebroplasy (PVP) might lead to significant radiation exposure to patients, operators, and operating room personnel. Therefore, radiaton exposure is a concern. The aim of this study was to present a remote control cement delivery device and study whether it can reduce dose exposue to operators. Methods After meticulous preoperative preparation, a series of 40 osteoporosis patients were treated with unilateral approach PVP using the new cement delivery divice. We compared levels of fluoroscopic exposure to operator standing on different places during operation. group A: operator stood about 4 meters away from X-ray tube behind the lead sheet. group B: operator stood adjacent to patient as using conventional manual cement delivery device. Results During whole operation process, radiation dose to the operator (group A) was 0.10 ± 0.03 (0.07-0.15) μSv, group B was 12.09 ± 4.67 (10–20) μSv. a difference that was found to be statistically significant (P < 0.001) between group A and group B. Conclusion New cement delivery device plus meticulous preoperative preparation can significantly decrease radiation dose to operators. PMID:25084860

  14. Long-term stable polymer solar cells with significantly reduced burn-in loss.

    PubMed

    Kong, Jaemin; Song, Suhee; Yoo, Minji; Lee, Ga Young; Kwon, Obum; Park, Jin Kuen; Back, Hyungcheol; Kim, Geunjin; Lee, Seoung Ho; Suh, Hongsuk; Lee, Kwanghee

    2014-01-01

    The inferior long-term stability of polymer-based solar cells needs to be overcome for their commercialization to be viable. In particular, an abrupt decrease in performance during initial device operation, the so-called 'burn-in' loss, has been a major contributor to the short lifetime of polymer solar cells, fundamentally impeding polymer-based photovoltaic technology. In this study, we demonstrate polymer solar cells with significantly improved lifetime, in which an initial burn-in loss is substantially reduced. By isolating trap-embedded components from pristine photoactive polymers based on the unimodality of molecular weight distributions, we are able to selectively extract a trap-free, high-molecular-weight component. The resulting polymer component exhibits enhanced power conversion efficiency and long-term stability without abrupt initial burn-in degradation. Our discovery suggests a promising possibility for commercial viability of polymer-based photovoltaics towards real solar cell applications. PMID:25483206

  15. Incorporation of catalytic dehydrogenation into fischer-tropsch synthesis to significantly reduce carbon dioxide emissions

    DOEpatents

    Huffman, Gerald P.

    2012-11-13

    A new method of producing liquid transportation fuels from coal and other hydrocarbons that significantly reduces carbon dioxide emissions by combining Fischer-Tropsch synthesis with catalytic dehydrogenation is claimed. Catalytic dehydrogenation (CDH) of the gaseous products (C1-C4) of Fischer-Tropsch synthesis (FTS) can produce large quantities of hydrogen while converting the carbon to multi-walled carbon nanotubes (MWCNT). Incorporation of CDH into a FTS-CDH plant converting coal to liquid fuels can eliminate all or most of the CO.sub.2 emissions from the water-gas shift (WGS) reaction that is currently used to elevate the H.sub.2 level of coal-derived syngas for FTS. Additionally, the FTS-CDH process saves large amounts of water used by the WGS reaction and produces a valuable by-product, MWCNT.

  16. Reduced respiratory neural activity elicits phrenic motor facilitation.

    PubMed

    Mahamed, Safraaz; Strey, Kristi A; Mitchell, Gordon S; Baker-Herman, Tracy L

    2011-03-15

    We hypothesized that reduced respiratory neural activity elicits compensatory mechanisms of plasticity that enhance respiratory motor output. In urethane-anesthetized and ventilated rats, we reversibly reduced respiratory neural activity for 25-30 min using: hypocapnia (end tidal CO(2)=30 mmHg), isoflurane (~1%) or high frequency ventilation (HFV; ~100 breaths/min). In all cases, increased phrenic burst amplitude was observed following restoration of respiratory neural activity (hypocapnia: 92±22%; isoflurane: 65±22%; HFV: 54±13% baseline), which was significantly greater than time controls receiving the same surgery, but no interruptions in respiratory neural activity (3±5% baseline, p<0.05). Hypocapnia also elicited transient increases in respiratory burst frequency (9±2 versus 1±1bursts/min, p<0.05). Our results suggest that reduced respiratory neural activity elicits a unique form of plasticity in respiratory motor control which we refer to as inactivity-induced phrenic motor facilitation (iPMF). iPMF may prevent catastrophic decreases in respiratory motor output during ventilatory control disorders associated with abnormal respiratory activity. PMID:21167322

  17. Reduced respiratory neural activity elicits phrenic motor facilitation

    PubMed Central

    Mahamed, Safraaz; Strey, Kristi A.; Mitchell, Gordon S.; Baker-Herman, Tracy L.

    2011-01-01

    We hypothesized that reduced respiratory neural activity elicits compensatory mechanisms of plasticity that enhance respiratory motor output. In urethane-anesthetized and ventilated rats, we reversibly reduced respiratory neural activity for 25–30 min using: hypocapnia (end tidal CO2 = 30 mmHg), isoflurane (~ 1%) or high frequency ventilation (HFV; ~100 breaths/min). In all cases, increased phrenic burst amplitude was observed following restoration of respiratory neural activity (hypocapnia: 92 ± 22%; isoflurane: 65 ± 22%; HFV: 54 ± 13% baseline), which was significantly greater than time controls receiving the same surgery, but no interruptions in respiratory neural activity (3 ± 5% baseline, p<0.05). Hypocapnia also elicited transient increases in respiratory burst frequency (9 ± 2 versus 1 ± 1 bursts/min, p<0.05). Our results suggest that reduced respiratory neural activity elicits a unique form of plasticity in respiratory motor control which we refer to as inactivity-induced phrenic motor facilitation (iPMF). iPMF may prevent catastrophic decreases in respiratory motor output during ventilatory control disorders associated with abnormal respiratory activity. PMID:21167322

  18. Inviting consumers to downsize fast-food portions significantly reduces calorie consumption.

    PubMed

    Schwartz, Janet; Riis, Jason; Elbel, Brian; Ariely, Dan

    2012-02-01

    Policies that mandate calorie labeling in fast-food and chain restaurants have had little or no observable impact on calorie consumption to date. In three field experiments, we tested an alternative approach: activating consumers' self-control by having servers ask customers if they wanted to downsize portions of three starchy side dishes at a Chinese fast-food restaurant. We consistently found that 14-33 percent of customers accepted the downsizing offer, and they did so whether or not they were given a nominal twenty-five-cent discount. Overall, those who accepted smaller portions did not compensate by ordering more calories in their entrées, and the total calories served to them were, on average, reduced by more than 200. We also found that accepting the downsizing offer did not change the amount of uneaten food left at the end of the meal, so the calorie savings during purchasing translated into calorie savings during consumption. Labeling the calorie content of food during one of the experiments had no measurable impact on ordering behavior. If anything, the downsizing offer was less effective in changing customers' ordering patterns with the calorie labeling present. These findings highlight the potential importance of portion-control interventions that specifically activate consumers' self-control. PMID:22323171

  19. Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy

    PubMed Central

    Lichter, David I.; Di Bacco, Alessandra; Blakemore, Stephen J.; Berger, Allison; Koenig, Erik; Bernard, Hugues; Trepicchio, William; Li, Bin; Neuwirth, Rachel; Chattopadhyay, Nibedita; Bolen, Joseph B.; Dorner, Andrew J.; van de Velde, Helgi; Ricci, Deborah; Jagannath, Sundar; Berenson, James R.; Richardson, Paul G.; Stadtmauer, Edward A.; Orlowski, Robert Z.; Lonial, Sagar; Anderson, Kenneth C.; Sonneveld, Pieter; San Miguel, Jesús F.; Esseltine, Dixie-Lee; Schu, Matthew

    2014-01-01

    Various translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41 known oncogenes and tumor suppressor genes in tumor samples from 133 relapsed myeloma patients participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were identified in 14 genes. BRAF as well as RAS genes were mutated in a large proportion of cases (45.9%) and these mutations were mutually exclusive. New recurrent mutations were also identified, including in the PDGFRA and JAK3 genes. NRAS mutations were associated with a significantly lower response rate to single-agent bortezomib (7% vs 53% in patients with mutant vs wild-type NRAS, P = .00116, Bonferroni-corrected P = .016), as well as shorter time to progression in bortezomib-treated patients (P = .0058, Bonferroni-corrected P = .012). However, NRAS mutation did not impact outcome in patients treated with high-dose dexamethasone. KRAS mutation did not reduce sensitivity to bortezomib or dexamethasone. These findings identify a significant clinical impact of NRAS mutation in myeloma and demonstrate a clear example of functional differences between the KRAS and NRAS oncogenes. PMID:24335104

  20. Neoadjuvant chemotherapy in breast cancer significantly reduces number of yielded lymph nodes by axillary dissection

    PubMed Central

    2014-01-01

    Background Neoadjuvant chemotherapy (NC) is an established therapy in breast cancer, able to downstage positive axillary lymph nodes, but might hamper their detectibility. Even if clinical observations suggest lower lymph node yield (LNY) after NC, data are inconclusive and it is unclear whether NC dependent parameters influence detection rates by axillary lymph node dissection (ALND). Methods We analyzed retrospectively the LNY in 182 patients with ALND after NC and 351 patients with primary ALND. Impact of surgery or pathological examination and specific histomorphological alterations were evaluated. Outcome analyses regarding recurrence rates, disease free (DFS) and overall survival (OS) were performed. Results Axillary LNY was significantly lower in the NC in comparison to the primary surgery group (median 13 vs. 16; p < 0.0001). The likelihood of incomplete axillary staging was four times higher in the NC group (14.8% vs. 3.4%, p < 0.0001). Multivariate analyses excluded any influence by surgeon or pathologist. However, the chemotherapy dependent histological feature lymphoid depletion was an independent predictive factor for a lower LNY. Outcome analyses revealed no significant impact of the LNY on local and regional recurrence rates as well as DFS and OS, respectively. Conclusion NC significantly reduces the LNY by ALND and has profound effects on the histomorphological appearance of lymph nodes. The current recommendations for a minimum removal of 10 lymph nodes by ALND are clearly compromised by the clinically already established concept of NC. The LNY of less than 10 by ALND after NC might not be indicative for an insufficient axillary staging. PMID:24386929

  1. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    PubMed

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. PMID:26524415

  2. Using lytic bacteriophages to eliminate or significantly reduce contamination of food by foodborne bacterial pathogens.

    PubMed

    Sulakvelidze, Alexander

    2013-10-01

    Bacteriophages (also called 'phages') are viruses that kill bacteria. They are arguably the oldest (3 billion years old, by some estimates) and most ubiquitous (total number estimated to be 10(30) -10(32) ) known organisms on Earth. Phages play a key role in maintaining microbial balance in every ecosystem where bacteria exist, and they are part of the normal microflora of all fresh, unprocessed foods. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention focused on using them to improve food safety. That approach, called 'phage biocontrol', typically includes three main types of applications: (i) using phages to treat domesticated livestock in order to reduce their intestinal colonization with, and shedding of, specific bacterial pathogens; (ii) treatments for decontaminating inanimate surfaces in food-processing facilities and other food establishments, so that foods processed on those surfaces are not cross-contaminated with the targeted pathogens; and (iii) post-harvest treatments involving direct applications of phages onto the harvested foods. This mini-review primarily focuses on the last type of intervention, which has been gaining the most momentum recently. Indeed, the results of recent studies dealing with improving food safety, and several recent regulatory approvals of various commercial phage preparations developed for post-harvest food safety applications, strongly support the idea that lytic phages may provide a safe, environmentally-friendly, and effective approach for significantly reducing contamination of various foods with foodborne bacterial pathogens. However, some important technical and nontechnical problems may need to be addressed before phage biocontrol protocols can become an integral part of routine food safety intervention strategies implemented by food industries in the USA. PMID:23670852

  3. Low level laser therapy reduces inflammation in activated Achilles tendinitis

    NASA Astrophysics Data System (ADS)

    Bjordal, Jan M.; Iversen, Vegard; Lopes-Martins, Rodrigo Alvaro B.

    2006-02-01

    Objective: Low level laser therapy (LLLT) has been forwarded as therapy for osteoarthritis and tendinopathy. Results in animal and cell studies suggest that LLLT may act through a biological mechanism of inflammatory modulation. The current study was designed to investigate if LLLT has an anti-inflammatory effect on activated tendinitis of the Achilles tendon. Methods: Seven patients with bilateral Achilles tendonitis (14 tendons) who had aggravated symptoms by pain-inducing activity immediately prior to the study. LLLT (1.8 Joules for each of three points along the Achilles tendon with 904nm infrared laser) and placebo LLLT were administered to either Achilles tendons in a random order to which patients and therapist were blinded. Inflammation was examined by 1) mini-invasive microdialysis for measuring the concentration of inflammatory marker PGE II in the peritendinous tissue, 2) ultrasound with Doppler measurement of peri- and intratendinous blood flow, 3) pressure pain algometry and 4) single hop test. Results: PGE 2- levels were significantly reduced at 75, 90 and 105 minutes after active LLLT compared both to pre-treatment levels (p=0.026) and to placebo LLLT (p=0.009). Changes in pressure pain threshold (PPT) were significantly different (P=0.012) between groups. PPT increased by a mean value of 0.19 kg/cm2 [95%CI:0.04 to 0.34] after treatment in the active LLLT group, while pressure pain threshold was reduced by -0.20 kg/cm2 [95%CI:-0.45 to 0.05] after placebo LLLT. Conclusion: LLLT can be used to reduce inflammatory musculskeletal pain as it reduces inflammation and increases pressure pain threshold levels in activity-induced pain episodes of Achilles tendinopathy.

  4. Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions.

    PubMed

    Bavishi, Chirag; Ather, Sameer; Bambhroliya, Arvind; Jneid, Hani; Virani, Salim S; Bozkurt, Biykem; Deswal, Anita

    2014-06-01

    Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/m(2), and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p <0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF. PMID:24837261

  5. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-10-07

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  6. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, G.G.; Kato, T.R.; Schonegg, E.

    1985-04-11

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed. 5 tabs.

  7. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-01-01

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  8. Lead Clinical and Preclinical Antimalarial Drugs Can Significantly Reduce Sporozoite Transmission to Vertebrate Populations

    PubMed Central

    Upton, L. M.; Brock, P. M.; Churcher, T. S.; Ghani, A. C.; Gething, P. W.; Delves, M. J.; Sala, K. A.; Leroy, D.; Sinden, R. E.

    2014-01-01

    To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual antimalarial drugs can impact the number of secondary Plasmodium berghei infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns. PMID:25385107

  9. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect

    PubMed Central

    Goudra, Basavana Gouda; Singh, Preet Mohinder; Penugonda, Lakshmi C; Speck, Rebecca M; Sinha, Ashish C

    2014-01-01

    Background: Providing anesthesia for gastrointestinal (GI) endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. Materials and Methods: This retrospective cohort study included patients with a body mass index (BMI) >40 kg/m2 that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. Results: A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA). These desaturation episodes were found to be statistically independent of increasing BMI of patients. Conclusion: Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation. PMID:24574597

  10. Magnitude and significance of the higher-order reduced density matrix cumulants

    NASA Astrophysics Data System (ADS)

    Herbert, John M.

    Using full configuration interaction wave functions for Be and LiH, in both minimal and extended basis sets, we examine the absolute magnitude and energetic significance of various contributions to the three-electron reduced density matrix (3-RDM) and its connected (size-consistent) component, the 3-RDM cumulant (3-RDMC). Minimal basis sets are shown to suppress the magnitude of the 3-RDMC in an artificial manner, whereas in extended basis sets, 3-RDMC matrix elements are often comparable in magnitude to the corresponding 3-RDM elements, even in cases where this result is not required by spin angular momentum coupling. Formal considerations suggest that these observations should generalize to higher-order p-RDMs and p-RDMCs (p > 3). This result is discussed within the context of electronic structure methods based on the contracted Schrödinger equation (CSE), as solution of the CSE relies on 3- and 4-RDM ?reconstruction functionals? that neglect the 3-RDMC, the 4-RDMC, or both. Although the 3-RDMC is responsible for at most 0.2% of the total electronic energy in Be and LiH, it accounts for up to 70% of the correlation energy, raising questions regarding whether (and how) the CSE can offer a useful computational methodology.

  11. Blockade of Mast Cell Activation Reduces Cutaneous Scar Formation

    PubMed Central

    Ranzer, Matthew J.; Wilgus, Traci A.; DiPietro, Luisa A.

    2014-01-01

    Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound. PMID:24465509

  12. Blockade of mast cell activation reduces cutaneous scar formation.

    PubMed

    Chen, Lin; Schrementi, Megan E; Ranzer, Matthew J; Wilgus, Traci A; DiPietro, Luisa A

    2014-01-01

    Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound. PMID:24465509

  13. Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

    PubMed Central

    Richards, Erica M.; Rosenthal, Robert E.; Kristian, Tibor; Fiskum, Gary

    2008-01-01

    The pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate and represents the sole bridge between anaerobic and aerobic cerebral energy metabolism. Previous studies demonstrating loss of PDHC enzyme activity and immunoreactivity during reperfusion after cerebral ischemia suggest that oxidative modifications are involved. This study tested the hypothesis that hyperoxic reperfusion exacerbates loss of PDHC enzyme activity, possibly due to tyrosine nitration or S-nitrosation. We used a clinically relevant canine ventricular fibrillation cardiac arrest model in which, after resuscitation and ventilation on either 100% O2 (hyperoxic) or 21–30% O2 (normoxic), animals were sacrificed at 2 h reperfusion and the brains removed for enzyme activity and immunoreactivity measurements. Animals resuscitated under hyperoxic conditions exhibited decreased PDHC activity and elevated 3-nitrotyrosine immunoreactivity in the hippocampus but not the cortex, compared to nonischemic controls. These measures were unchanged in normoxic animals. In vitro exposure of purified PDHC to peroxynitrite resulted in a dose-dependent loss of activity and increased nitrotyrosine immunoreactivity. These results support the hypothesis that oxidative stress contributes to loss of hippocampal PDHC activity during cerebral ischemia and reperfusion and suggest that PDHC is a target of peroxynitrite. PMID:16716897

  14. Reduced Variability of Auditory Alpha Activity in Chronic Tinnitus

    PubMed Central

    Schecklmann, Martin; Kreuzer, Peter M.; Vielsmeier, Veronika; Poeppl, Timm B.; Langguth, Berthold

    2014-01-01

    Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8–10 Hz) but not for the upper alpha band (10–12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus. PMID:24967106

  15. Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug

    PubMed Central

    Svensson, Elin M.; Murray, Stephen; Karlsson, Mats O.; Dooley, Kelly E.

    2015-01-01

    Objectives Bedaquiline is the first drug of a new class approved for the treatment of TB in decades. Bedaquiline is metabolized by cytochrome P450 (CYP) 3A4 to a less-active M2 metabolite. Its terminal half-life is extremely long (5–6 months), complicating evaluations of drug–drug interactions. Rifampicin and rifapentine, two anti-TB drugs now being optimized to shorten TB treatment duration, are potent inducers of CYP3A4. This analysis aimed to predict the effect of repeated doses of rifampicin or rifapentine on the steady-state pharmacokinetics of bedaquiline and its M2 metabolite from single-dose data using a model-based approach. Methods Pharmacokinetic data for bedaquiline and M2 were obtained from a Phase I study involving 32 individuals each receiving two doses of bedaquiline, alone or together with multiple-dose rifampicin or rifapentine. Sampling was performed over 14 days following each bedaquiline dose. Pharmacokinetic analyses were performed using non-linear mixed-effects modelling. Models were used to simulate potential dose adjustments. Results Rifamycin co-administration increased bedaquiline clearance substantially: 4.78-fold [relative standard error (RSE) 9.10%] with rifampicin and 3.96-fold (RSE 5.00%) with rifapentine. Induction of M2 clearance was equally strong. Average steady-state concentrations of bedaquiline and M2 are predicted to decrease by 79% and 75% when given with rifampicin or rifapentine, respectively. Simulations indicated that increasing the bedaquiline dosage to mitigate the interaction would yield elevated M2 concentrations during the first treatment weeks. Conclusions Rifamycin antibiotics reduce bedaquiline concentrations substantially. In line with current treatment guidelines for drug-susceptible TB, concomitant use is not recommended, even with dose adjustment. PMID:25535219

  16. Sulfide-driven autotrophic denitrification significantly reduces N2O emissions.

    PubMed

    Yang, Weiming; Zhao, Qing; Lu, Hui; Ding, Zhi; Meng, Liao; Chen, Guang-Hao

    2016-03-01

    The Sulfate reduction-Autotrophic denitrification-Nitrification Integrated (SANI) process build on anaerobic carbon conversion through biological sulfate reduction and autotrophic denitrification by using the sulfide byproduct from the previous reaction. This study confirmed extra decreases in N2O emissions from the sulfide-driven autotrophic denitrification by investigating N2O reduction, accumulation, and emission in the presence of different sulfide/nitrate (S/N) mass ratios at pH 7 in a long-term laboratory-scale granular sludge autotrophic denitrification reactor. The N2O reduction rate was linearly proportional to the sulfide concentration, which confirmed that no sulfide inhibition of N2O reductase occurred. At S/N = 5.0 g-S/g-N, this rate resulted by sulfide-driven autotrophic denitrifying granular sludge (average granule size = 701 μm) was 27.7 mg-N/g-VSS/h (i.e., 2 and 4 times greater than those at 2.5 and 0.8 g-S/g-N, respectively). Sulfide actually stimulates rather than inhibits N2O reduction no matter what granule size of sulfide-driven autotrophic denitrifying sludge engaged. The accumulations of N2O, nitrite and free nitrous acid (FNA) with average granule size 701 μm of sulfide-driven autotrophic denitrifying granular sludge engaged at S/N = 5.0 g-S/g-N were 4.7%, 11.4% and 4.2% relative to those at 3.0 g-S/g-N, respectively. The accumulation of FNA can inhibit N2O reduction and increase N2O accumulation during sulfide-driven autotrophic denitrification. In addition, the N2O gas emission level from the reactor significantly increased from 14.1 ± 0.5 ppmv (0.002% of the N load) to 3707.4 ± 36.7 ppmv (0.405% of the N load) as the S/N mass ratio in the influent decreased from 2.1 to 1.4 g-S/g-N over the course of the 120-day continuous monitoring period. Sulfide-driven autotrophic denitrification may significantly reduce greenhouse gas emissions from biological nutrient removal when sulfur conversion processes are applied. PMID

  17. Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study

    PubMed Central

    Wang, Yongbo; Gao, Xiang; Pedram, Pardis; Shahidi, Mariam; Du, Jianling; Yi, Yanqing; Gulliver, Wayne; Zhang, Hongwei; Sun, Guang

    2016-01-01

    Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%–27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile. PMID:26742059

  18. Reducing the endotoxic activity of pertussis vaccine.

    PubMed Central

    Bannatyne, R. M.; Cheung, R.

    1981-01-01

    Unadsorbed, regular production pertussis vaccine was treated with polymyxin B sulphate at concentrations of 25, 50 and 100 microgram/ml. The toxic activity of treated and untreated vaccines was compared using both the limulus amoebocyte lysate test and the mouse-weight-gain test. Protective efficacy was also assessed by the mouse protection test. No discernible effect on either toxicity or efficacy of the pertussis vaccine was observed. When the vaccine was treated with 5000 microgram/ml of polymyxin, endotoxic activity assessed by the limulus lysate test appeared to be abolished. PMID:7310121

  19. Behavioral intervention to reduce AIDS risk activities.

    PubMed

    Kelly, J A; St Lawrence, J S; Hood, H V; Brasfield, T L

    1989-02-01

    Behavior change can curtail the spread of acquired immune deficiency syndrome (AIDS). In this study, 104 gay men with a history of frequent AIDS high-risk behavior completed self-report, self-monitoring, and behavioral measures related to AIDS risk. The sample was randomly divided into experimental and waiting-list control groups. The experimental intervention provided AIDS risk education, cognitive-behavioral self-management training, sexual assertion training, and attention to the development of steady and self-affirming social supports. Experimental group participants greatly reduced their frequency of high-risk sexual practices and increased behavioral skills for refusing sexual coercions, AIDS risk knowledge, and adoption of "safer sex" practices. Change was maintained at the 8-month follow-up. PMID:2925974

  20. Mucin Binding Reduces Colistin Antimicrobial Activity

    PubMed Central

    Huang, Johnny X.; Blaskovich, Mark A. T.; Pelingon, Ruby; Ramu, Soumya; Kavanagh, Angela; Elliott, Alysha G.; Butler, Mark S.

    2015-01-01

    Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance. PMID:26169405

  1. Performance evaluation of hydrological models: Statistical significance for reducing subjectivity in goodness-of-fit assessments

    NASA Astrophysics Data System (ADS)

    Ritter, Axel; Muñoz-Carpena, Rafael

    2013-02-01

    SummarySuccess in the use of computer models for simulating environmental variables and processes requires objective model calibration and verification procedures. Several methods for quantifying the goodness-of-fit of observations against model-calculated values have been proposed but none of them is free of limitations and are often ambiguous. When a single indicator is used it may lead to incorrect verification of the model. Instead, a combination of graphical results, absolute value error statistics (i.e. root mean square error), and normalized goodness-of-fit statistics (i.e. Nash-Sutcliffe Efficiency coefficient, NSE) is currently recommended. Interpretation of NSE values is often subjective, and may be biased by the magnitude and number of data points, data outliers and repeated data. The statistical significance of the performance statistics is an aspect generally ignored that helps in reducing subjectivity in the proper interpretation of the model performance. In this work, approximated probability distributions for two common indicators (NSE and root mean square error) are derived with bootstrapping (block bootstrapping when dealing with time series), followed by bias corrected and accelerated calculation of confidence intervals. Hypothesis testing of the indicators exceeding threshold values is proposed in a unified framework for statistically accepting or rejecting the model performance. It is illustrated how model performance is not linearly related with NSE, which is critical for its proper interpretation. Additionally, the sensitivity of the indicators to model bias, outliers and repeated data is evaluated. The potential of the difference between root mean square error and mean absolute error for detecting outliers is explored, showing that this may be considered a necessary but not a sufficient condition of outlier presence. The usefulness of the approach for the evaluation of model performance is illustrated with case studies including those with

  2. The Significance of Ras Activity in Pancreatic Cancer Initiation

    PubMed Central

    Logsdon, Craig D.; Lu, Weiqin

    2016-01-01

    The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

  3. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... accrual or that eliminates or significantly reduces an early retirement benefit or retirement-type subsidy... or reduces an early retirement benefit or retirement-type subsidy for purposes of determining whether... retirement-type subsidy is significant for purposes of section 4980F and section 204(h)? Q-9. When...

  4. Reduced active thyroid hormone levels after delivery.

    PubMed

    Banovac, K; Kekić, M; Bzik, L; Skreb, F; Sekso, M

    1981-01-01

    The effect of delivery on the serum concentration of thyroid hormones was studied in 25 euthyroid women. After delivery serum free and total T3 and T4 fell transiently with a simultaneous increase in reverse T3 while serum TSH and thyroxine binding globulin (TBG) concentrations showed no significant variation. These data suggest that i) similar to what happens in other stressful situations, delivery influences peripheral T4 metabolism, and ii) an elevation of TBG in serum in the early puerperium does not prevent these changes. PMID:6798093

  5. Adaptive significance of right hemisphere activation in aphasic language comprehension.

    PubMed

    Meltzer, Jed A; Wagage, Suraji; Ryder, Jennifer; Solomon, Beth; Braun, Allen R

    2013-06-01

    Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible ("The boy is eating the apple") and reversible ("The boy is pushing the girl") sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia. PMID:23566891

  6. Rural Enterprises, Incorporated report of significant activities and accomplishments

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The ongoing activities of Rural Enterprises, Inc. are presented. The function of Rural Enterprises is to bring innovation from its rudimentary conceptual stages to useful and productive ends by means of cooperation with government, business, and educational institutions.

  7. Distribution and significance of heterotrophic marine bacteria with antibacterial activity.

    PubMed Central

    Nair, S; Simidu, U

    1987-01-01

    Bacteria with antibacterial activity were isolated from seawater, sediments, phytoplankton, and zooplankton of Suruga, Sagami, and Tokyo Bays and from soft corals and sponges collected from the Taiwan coast. Of the 726 strains isolated, 37 showed antibacterial activity against either Vibrio parahaemolyticus (ATCC 17802) or Staphylococcus aureus (P209). Sediment harbored the lowest number of these forms of bacteria, and those from Tokyo Bay did not show any activity. Attached isolates showed greater activity compared with free-living forms. Relatively high numbers of strains with antibacterial activity were associated with phytoplankton. Among the zooplankton isolates, cladocerans harbored the maximum number of antibacterial strains. Isolates were more inhibitory to gram-positive test cultures. Autoinhibition was observed only among 8% of the isolates. Marine nonproducers were more susceptible. Pseudomonas/Alteromonas species made up 81.0% of isolates, of which 30% were pigmented strains. The absence or reduction in number of bacteria with antibacterial activity in Tokyo Bay is attributed to its eutrophic nature, which may tend to moderate the production of antibacterial compounds. PMID:3435149

  8. Routine activities and victimization at school: the significance of gender.

    PubMed

    Popp, Ann Marie; Peguero, Anthony A

    2011-08-01

    Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a gender-specific relationship with victimization. This article explores the importance of gender in understanding the relationship between student's participation in extracurricular routine activities (e.g., student government, clubs, sports, and etc.) and the risk of victimization. From the Education Longitudinal Study of 2002, a sample of 10th-grade students was drawn for analyses. Hierarchical Generalized Linear Modeling was employed to explore the role of gender in the relationship between extracurricular routine activities and victimization at school. The results reveal that students' gender indeed interacts with several of the extracurricular routine activities creating gender-specific risks of victimization. This article highlights the importance of gender in explaining victimization and suggests researchers should consider how gender may interact with other routine activities and victimization. PMID:20956442

  9. Large roads reduce bat activity across multiple species.

    PubMed

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations. PMID:24823689

  10. Large Roads Reduce Bat Activity across Multiple Species

    PubMed Central

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations. PMID:24823689

  11. Soil nitrate reducing processes – drivers, mechanisms for spatial variation, and significance for nitrous oxide production

    PubMed Central

    Giles, Madeline; Morley, Nicholas; Baggs, Elizabeth M.; Daniell, Tim J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3−) and production of the potent greenhouse gas, nitrous oxide (N2O). A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub centimeter areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location, and potential for N2O production from soils. PMID:23264770

  12. Knee loading reduces MMP13 activity in the mouse cartilage

    PubMed Central

    2013-01-01

    Background Moderate loads with knee loading enhance bone formation, but its effects on the maintenance of the knee are not well understood. In this study, we examined the effects of knee loading on the activity of matrix metalloproteinase13 (MMP13) and evaluated the role of p38 MAPK and Rac1 GTPase in the regulation of MMP13. Methods Knee loading (0.5–3 N for 5 min) was applied to the right knee of surgically-induced osteoarthritis (OA) mice as well as normal (non-OA) mice, and MMP13 activity in the femoral cartilage was examined. The sham-loaded knee was used as a non-loading control. We also employed primary non-OA and OA human chondrocytes as well as C28/I2 chondrocyte cells, and examined MMP13 activity and molecular signaling in response to shear at 2–20 dyn/cm2. Results Daily knee loading at 1 N for 2 weeks suppressed cartilage destruction in the knee of OA mice. Induction of OA elevated MMP13 activity and knee loading at 1 N suppressed this elevation. MMP13 activity was also increased in primary OA chondrocytes, and this increase was attenuated by applying shear at 10 dyn/cm2. Load-driven reduction in MMP13 was associated with a decrease in the phosphorylation level of p38 MAPK (p-p38) and NFκB (p-NFκB). Molecular imaging using a fluorescence resonance energy transfer (FRET) technique showed that Rac1 activity was reduced by shear at 10 dyn/cm2 and elevated by it at 20 dyn/cm2. Silencing Rac1 GTPase significantly reduced MMP13 expression and p-p38 but not p-NFκB. Transfection of a constitutively active Rac1 GTPase mutant increased MMP13 activity, while a dominant negative mutant decreased it. Conclusions Knee loading reduces MMP13 activity at least in part through Rac1-mediated p38 MAPK signaling. This study suggests the possibility of knee loading as a therapy not only for strengthening bone but also preventing tissue degradation of the femoral cartilage. PMID:24180431

  13. Strategies to reduce dendritic cell activation through functional biomaterial design

    PubMed Central

    Hume, Patrick S.; He, Jing; Haskins, Kathryn; Anseth, Kristi S.

    2012-01-01

    Dendritic cells play a key role in determining adaptive immunity, and there is growing interest in characterizing and manipulating the interactions between dendritic cells and biomaterial surfaces. Contact with several common biomaterials can induce the maturation of immature dendritic cells, but substrates that reduce dendritic cell maturation are of particular interest within the field of cell-based therapeutics where the goal is to reduce the immune response to cell-laden material carriers. In this study, we use a materials-based strategy to functionalize poly(ethylene glycol) hydrogels with immobilized immunosuppressive factors (TGF-β1 and IL-10) to reduce the maturation of immature dendritic cells. TGF-β1 and IL-10 are commonly employed as soluble factors to program dendritic cells in vitro, and we demonstrate that these proteins retain bioactivity towards dendritic cells when immobilized on hydrogel surfaces. Following stimulation with lipopolysaccharide (LPS) and/or cytokines, a dendritic cell line interacting with the surfaces of immunosuppressive hydrogels expressed reduced markers of maturation, including IL-12 and MHCII. The bioactivity of these immunomodulatory hydrogels was further confirmed with primary bone marrow dendritic cells (BMDCs) isolated from non-obese diabetic (NOD) mice, as quantified by a decrease in activation markers and a significantly reduced capacity to activate T cells. Furthermore, by introducing a second signal to promote BMDC-material interactions combined with the presentation of tolerizing signals, the mulitfunctional PEG hydrogels were found to further increase signaling towards BMDCs, as evidenced by greater reductions in maturation markers. PMID:22361099

  14. Routine Activities and Victimization at School: The Significance of Gender

    ERIC Educational Resources Information Center

    Popp, Ann Marie; Peguero, Anthony A.

    2011-01-01

    Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a…

  15. The Potential for Bayesian Compressive Sensing to Significantly Reduce Electron Dose in High Resolution STEM Images

    SciTech Connect

    Stevens, Andrew J.; Yang, Hao; Carin, Lawrence; Arslan, Ilke; Browning, Nigel D.

    2014-02-11

    The use of high resolution imaging methods in the scanning transmission electron microscope (STEM) is limited in many cases by the sensitivity of the sample to the beam and the onset of electron beam damage (for example in the study of organic systems, in tomography and during in-situ experiments). To demonstrate that alternative strategies for image acquisition can help alleviate this beam damage issue, here we apply compressive sensing via Bayesian dictionary learning to high resolution STEM images. These experiments successively reduce the number of pixels in the image (thereby reducing the overall dose while maintaining the high resolution information) and show promising results for reconstructing images from this reduced set of randomly collected measurements. We show that this approach is valid for both atomic resolution images and nanometer resolution studies, such as those that might be used in tomography datasets, by applying the method to images of strontium titanate and zeolites. As STEM images are acquired pixel by pixel while the beam is scanned over the surface of the sample, these post acquisition manipulations of the images can, in principle, be directly implemented as a low-dose acquisition method with no change in the electron optics or alignment of the microscope itself.

  16. Finding Significant Correlates of Conscious Activity in Rhythmic EEG

    NASA Astrophysics Data System (ADS)

    Durka, Piotr J.

    2005-12-01

    One of the important issues in designing an EEG-based brain-computer interface is an exact delineation of the rhythms, related to the intended or performed action. Traditionally, related bands were found by trial and error procedures seeking maximum reactivity. Even then, large values of ERD/ERS did not imply the statistical significance of the results. This paper presents complete methodology, allowing for a high-resolution presentation of the whole time-frequency picture of event-related changes in the energy density of signals, revealing the microstructure of rhythms, and determination of the time-frequency regions of energy changes, which are related to the intentions in a statistically significant way.

  17. Reduced brain activation in violent adolescents during response inhibition

    PubMed Central

    Qiao, Yi; Mei, Yi; Du, XiaoXia; Xie, Bin; Shao, Yang

    2016-01-01

    Deficits in inhibitory control have been linked to aggression and violent behaviour. This study aimed to observe whether violent adolescents show different brain activation patterns during response inhibition and to ascertain the roles these brain regions play. A self-report method and modified overt aggression scale (MOAS) were used to evaluate violent behaviour. Functional magnetic resonance imaging was performed in 22 violent adolescents and 17 matched healthy subjects aged 12 to 18 years. While scanning, a go/no-go task was performed. Between-group comparisons revealed that activation in the bilateral middle and superior temporal gyrus, hippocampus, and right orbitofrontal area (BA11) regions were significantly reduced in the violent group compared with the control group. Meanwhile, the violent group had more widespread activation in the prefrontal cortex than that observed in the control group. Activation of the prefrontal cortex in the violent group was widespread but lacking in focus, failing to produce intensive activation in some functionally related regions during response inhibition. PMID:26888566

  18. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus.

    PubMed

    Yamamoto, Nobuto; Urade, Masahiro

    2005-04-01

    Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The precursor activity of serum Gc protein was reduced in all influenza virus-infected patients. These patient sera contained alpha-N-acetylgalactosaminidase (Nagalase) that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to MAF, thus it loses the MAF precursor activity, leading to immunosuppression. An influenza virus stock contained a large amount of Nagalase activity. A sucrose gradient centrifugation analysis of the virus stock showed that the profile of Nagalase activity corresponds to that of hemagglutinating activity. When these gradient fractions were treated with 0.01% trypsin for 30 min, the Nagalase activity of each fraction increased significantly, suggesting that the Nagalase activity resides on an outer envelope protein of the influenza virion and is enhanced by the proteolytic process. After disruption of influenza virions with sodium deoxycholate, fractionation of the envelope proteins with mannose-specific lectin affinity column along with electrophoretic analysis of the Nagalase peak fraction revealed that Nagalase is the intrinsic component of the hemagglutinin (HA). Cloned HA protein exhibited Nagalase activity only if treated with trypsin. Since both fusion capacity and Nagalase activity of HA protein are expressed by proteolytic cleavage, Nagalase activity appears to be an enzymatic basis for the fusion process. Thus, Nagalase plays dual roles in regulating both infectivity and immunosuppression. PMID:15848273

  19. Does maintaining a bottle of adhesive without the lid significantly reduce the solvent content?

    PubMed

    Santana, Márcia Luciana Carregosa; Sousa Júnior, José Aginaldo de; Leal, Pollyana Caldeira; Faria-e-Silva, André Luis

    2014-01-01

    This study aimed to evaluate the effect of maintaining a bottle of adhesive without its lid on the solvent loss of the etch-and-rinse adhesive systems. Three 2-step etch-and-rinse adhesives with different solvents (acetone, ethanol or butanol) were used in this study. Drops of each adhesive were placed on an analytical balance and the adhesive mass was recorded until equilibrium was achieved (no significant mass alteration within time). The solvent content of each adhesive and evaporation rate of solvents were measured (n=3). Two bottles of each adhesive were weighted. The bottles were maintained without their lids for 8 h in a stove at 37 ºC, after which the mass loss was measured. Based on mass alteration of drops, acetone-based adhesive showed the highest solvent content (46.5%, CI 95%: 35.8-54.7) and evaporation rate (1.11 %/s, CI95%: 0.63-1.60), whereas ethanol-based adhesive had the lowest values (10.1%, CI95%: 4.3-16.0; 0.03 %/s CI95%: 0.01-0.05). However, none of the adhesives bottles exhibited significant mass loss after sitting for 8 h without their lids (% from initial content; acetone - 96.5, CI 95%: 91.8-101.5; ethanol - 99.4, CI 95%: 98.4-100.4; and butanol - 99.3, CI 95%: 98.1-100.5). In conclusion, maintaining the adhesive bottle without lid did not induce significant solvent loss, irrespective the concentration and evaporation rate of solvent. PMID:25590203

  20. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    SciTech Connect

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  1. Can remotely sensed meteorological data significantly contribute to reduce costs of tsetse surveys?

    PubMed

    Hendrickx, G; Napala, A; Rogers, D; Bastiaensen, P; Slingenbergh, J

    1999-01-01

    A 0.125 degree raster or grid-based Geographic Information System with data on tsetse, trypanosomiasis animal production, agriculturerkina> and land use has recently been developed in Togo. This paper addresses the problem of generating tsetse distribution and abundance maps from remotely sensed data, using a restricted amount of field data. A discriminant analysis model is tested using contemporary tsetse data and remotely sensed, low resolution data acquired from the National Oceanographic and Atmospheric Administration and Meteosat platforms. A split sample technique is adopted where a randomly selected part of the field measured data (training set) serves to predict the other part (predicted set). The obtained results are then compared with field measured data per corresponding grid-square. Depending on the size of the training set the percentage of concording predictions varies from 80 to 95 for distribution figures and from 63 to 74 for abundance. These results confirm the potential of satellite data application and multivariate analysis for the prediction, not only of the tsetse distribution, but more importantly of their abundance. This opens up new avenues because satellite predictions and field data may be combined to strengthen or substitute one another and thus reduce costs of field surveys. PMID:10224542

  2. Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling

    PubMed Central

    Ying, Zhekang; Chen, Minjie; Xie, Xiaoyun; Wang, Xiaoke; Kherada, Nisharahmed; Desikan, Rajagopal; Mihai, Georgeta; Burns, Patrick; Sun, Qinghua; Rajagopalan, Sanjay

    2016-01-01

    Objective Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2. Methods and Results Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages. Conclusion Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis. PMID:26859892

  3. Cleanroom Maintenance Significantly Reduces Abundance but Not Diversity of Indoor Microbiomes

    PubMed Central

    Mahnert, Alexander; Vaishampayan, Parag; Probst, Alexander J.; Auerbach, Anna; Moissl-Eichinger, Christine; Venkateswaran, Kasthuri; Berg, Gabriele

    2015-01-01

    Cleanrooms have been considered microbially-reduced environments and are used to protect human health and industrial product assembly. However, recent analyses have deciphered a rather broad diversity of microbes in cleanrooms, whose origin as well as physiological status has not been fully understood. Here, we examined the input of intact microbial cells from a surrounding built environment into a spacecraft assembly cleanroom by applying a molecular viability assay based on propidium monoazide (PMA). The controlled cleanroom (CCR) was characterized by ~6.2*103 16S rRNA gene copies of intact bacterial cells per m2 floor surface, which only represented 1% of the total community that could be captured via molecular assays without viability marker. This was in contrast to the uncontrolled adjoining facility (UAF) that had 12 times more living bacteria. Regarding diversity measures retrieved from 16S rRNA Illumina-tag analyzes, we observed, however, only a minor drop in the cleanroom facility allowing the conclusion that the number but not the diversity of microbes is strongly affected by cleaning procedures. Network analyses allowed tracking a substantial input of living microbes to the cleanroom and a potential enrichment of survival specialists like bacterial spore formers and archaeal halophiles and mesophiles. Moreover, the cleanroom harbored a unique community including 11 exclusive genera, e.g., Haloferax and Sporosarcina, which are herein suggested as indicators of cleanroom environments. In sum, our findings provide evidence that archaea are alive in cleanrooms and that cleaning efforts and cleanroom maintenance substantially decrease the number but not the diversity of indoor microbiomes. PMID:26273838

  4. Bacteriophage Combinations Significantly Reduce Clostridium difficile Growth In Vitro and Proliferation In Vivo

    PubMed Central

    Nale, Janet Y.; Spencer, Janice; Hargreaves, Katherine R.; Buckley, Anthony M.; Trzepiński, Przemysław

    2015-01-01

    The microbiome dysbiosis caused by antibiotic treatment has been associated with both susceptibility to and relapse of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity and dose amplification in situ, but few studies have focused on its use in CDI treatment. This mainly reflects the lack of strictly virulent phages that target this pathogen. While it is widely accepted that temperate phages are unsuitable for therapeutic purposes due to their transduction potential, analysis of seven C. difficile phages confirmed that this impact could be curtailed by the application of multiple phage types. Here, host range analysis of six myoviruses and one siphovirus was conducted on 80 strains representing 21 major epidemic and clinically severe ribotypes. The phages had complementary coverage, lysing 18 and 62 of the ribotypes and strains tested, respectively. Single-phage treatments of ribotype 076, 014/020, and 027 strains showed an initial reduction in the bacterial load followed by the emergence of phage-resistant colonies. However, these colonies remained susceptible to infection with an unrelated phage. In contrast, specific phage combinations caused the complete lysis of C. difficile in vitro and prevented the appearance of resistant/lysogenic clones. Using a hamster model, the oral delivery of optimized phage combinations resulted in reduced C. difficile colonization at 36 h postinfection. Interestingly, free phages were recovered from the bowel at this time. In a challenge model of the disease, phage treatment delayed the onset of symptoms by 33 h compared to the time of onset of symptoms in untreated animals. These data demonstrate the therapeutic potential of phage combinations to treat CDI. PMID:26643348

  5. Significantly reduced thermal diffusivity of free-standing two-layer graphene in graphene foam.

    PubMed

    Lin, Huan; Xu, Shen; Wang, Xinwei; Mei, Ning

    2013-10-18

    We report on a thermal diffusivity study of suspended graphene foam (GF) using the transient electro-thermal technique. Our Raman study confirms the GF is composed of two-layer graphene. By measuring GF of different lengths, we are able to exclude the radiation effect. Using Schuetz's model, the intrinsic thermal diffusivity of the free-standing two-layer graphene is determined with a high accuracy without using knowledge of the porosity of the GF. The intrinsic thermal diffusivity of the two-layer graphene is determined at 1.16-2.22 × 10(-4) m(2) s(-1). The corresponding intrinsic thermal conductivity is 182-349 W m(-1) K(-1), about one order of magnitude lower than those reported for single-layer graphene. Extensive surface impurity defects, wrinkles and rough edges are observed under a scanning electron microscope for the studied GF. These structural defects induce substantial phonon scattering and explain the observed significant thermal conductivity reduction. Our thermal diffusivity characterization of GF provides an advanced way to look into the thermal transport capacity of free-standing graphene with high accuracy and ease of experimental implementation. PMID:24060813

  6. Social networking strategies that aim to reduce obesity have achieved significant although modest results.

    PubMed

    Ashrafian, Hutan; Toma, Tania; Harling, Leanne; Kerr, Karen; Athanasiou, Thanos; Darzi, Ara

    2014-09-01

    The global epidemic of obesity continues to escalate. Obesity accounts for an increasing proportion of the international socioeconomic burden of noncommunicable disease. Online social networking services provide an effective medium through which information may be exchanged between obese and overweight patients and their health care providers, potentially contributing to superior weight-loss outcomes. We performed a systematic review and meta-analysis to assess the role of these services in modifying body mass index (BMI). Our analysis of twelve studies found that interventions using social networking services produced a modest but significant 0.64 percent reduction in BMI from baseline for the 941 people who participated in the studies' interventions. We recommend that social networking services that target obesity should be the subject of further clinical trials. Additionally, we recommend that policy makers adopt reforms that promote the use of anti-obesity social networking services, facilitate multistakeholder partnerships in such services, and create a supportive environment to confront obesity and its associated noncommunicable diseases. PMID:25201670

  7. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

    PubMed Central

    Sung, Nak Yoon

    2015-01-01

    Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation. PMID:26330757

  8. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study.

    PubMed

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-12-01

    Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77-0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID:26683907

  9. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    NASA Astrophysics Data System (ADS)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

  10. Varying protein source and quantity does not significantly improve weight loss, fat loss, or satiety in reduced energy diets among midlife adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This pilot study tested whether varying protein source and quantity in a reduced energy diet would result in significant differences in weight, body composition, and renin angiotensin aldosterone system activity in midlife adults. Eighteen subjects enrolled in a 5 month weight reduction study, invol...

  11. Recreational Activities to Reduce Behavioural Symptoms in Dementia

    PubMed Central

    Kolanowski, Ann; Fick, Donna M.; Buettner, Linda

    2009-01-01

    Few clinicians have an educational grounding in the use of nonpharmacological therapies for people with dementia. In this article, we explore the utility of recreational activities as one nonpharmacological intervention that has demonstrated effectiveness for reducing the behavioural symptoms of dementia. The implementation of effective recreational activities involves three components: understanding the evidence for this approach; acknowledging the need to reduce medications that have the potential to interfere with activity effectiveness; and individualizing activities so that the maximum benefit from the intervention is obtained. PMID:20046903

  12. Baicalein Reduces the Invasion of Glioma Cells via Reducing the Activity of p38 Signaling Pathway

    PubMed Central

    Lei, Xiaoming; Li, Siyuan; Zhang, Yong; Meng, Lihua; Xue, Rongliang; Li, Zongfang

    2014-01-01

    Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s) in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin) could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma. PMID:24587321

  13. Taurolidine-citrate lock solution (TauroLock) significantly reduces CVAD-associated grampositive infections in pediatric cancer patients

    PubMed Central

    Simon, Arne; Ammann, Roland A; Wiszniewsky, Gertrud; Bode, Udo; Fleischhack, Gudrun; Besuden, Mette M

    2008-01-01

    Background Taurolidin/Citrate (TauroLock™), a lock solution with broad spectrum antimicrobial activity, may prevent bloodstream infection (BSI) due to coagulase-negative staphylococci (CoNS or 'MRSE' in case of methicillin-resistant isolates) in pediatric cancer patients with a long term central venous access device (CVAD, Port- or/Broviac-/Hickman-catheter type). Methods In a single center prospective 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 (group 1, heparin lock with 200 IU/ml sterile normal saline 0.9%; Canusal® Wockhardt UK Ltd, Wrexham, Wales) and all patients from April 2005 to March 2007 (group 2; taurolidine 1.35%/Sodium Citrate 4%; TauroLock™, Tauropharm, Waldbüttelbrunn, Germany). Results In group 1 (heparin), 90 patients had 98 CVAD in use during the surveillance period. 14 of 30 (47%) BSI were 'primary Gram positive BSI due to CoNS (n = 4) or MRSE (n = 10)' [incidence density (ID); 2.30 per 1000 inpatient CVAD-utilization days]. In group 2 (TauroLock™), 89 patients had 95 CVAD in use during the surveillance period. 3 of 25 (12%) BSI were caused by CoNS. (ID, 0.45). The difference in the ID between the two groups was statistically significant (P = 0.004). Conclusion The use of Taurolidin/Citrate (TauroLock™) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients. PMID:18664278

  14. High-frequency TRNS reduces BOLD activity during visuomotor learning.

    PubMed

    Saiote, Catarina; Polanía, Rafael; Rosenberger, Konstantin; Paulus, Walter; Antal, Andrea

    2013-01-01

    Transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI). We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1-100 Hz; hf-tRNS 101-640 Hz, respectively) and sham stimulation over the primary motor cortex (M1) during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods. PMID:23527247

  15. Cathepsin G activity lowers plasma LDL and reduces atherosclerosis

    PubMed Central

    Wang, Jing; Sjöberg, Sara; Tang, Ting-Ting; Öörni, Katariina; Wu, Wenxue; Liu, Conglin; Secco, Blandine; Tia, Viviane; Sukhova, Galina K.; Fernandes, Cleverson; Lesner, Adam; Kovanen, Petri T.; Libby, Peter; Cheng, Xiang; Shi, Guo-Ping

    2014-01-01

    Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr−/−) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3 months. When mice consume this diet for 6 months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r= −0.535, P<0.0001) and LDL cholesterol (r= −0.559, P<0.0001), but not with HDL cholesterol (P=0.901) or triglycerides (P=0.186). Such inverse correlations with total cholesterol (r= −0.504, P<0.0001) and LDL cholesterol (r= −0.502, P<0.0001) remain significant after adjusting for lipid lowering treatments among this patient population. Human CatG degrades purified human LDL, but not HDL. This study suggests that CatG promotes early atherogenesis through its elastinolytic activity, but suppresses late progression of atherosclerosis by degrading LDL without affecting HDL or triglycerides. PMID:25092171

  16. Prognostic significance of reduced immunohistochemical expression of E-cadherin in endometrial cancer-results of a meta-analysis

    PubMed Central

    Zheng, Xing; Du, Xue-Lian; Jiang, Tao

    2015-01-01

    Objective: Previous studies which investigated the relationship between reduced E-cadherin and prognosis of endometrial cancer were ambiguous and conflicting. Therefore, the aim of the present study was to evaluate the relationship between reduced expression of E-cadherin and endometrial cancer by meta-analysis approach. Method: AfterPubmed and Embasewere deliberately searched via the internet, 8 pieces of literaturewere totally included in final meta-analysis. After the data had been abstracted, the pulled odds ratio (OR) and hazard ratio (HR) were calculated by STATA with random or fixed effect model depending on their heterogeneity. The publication bias of included literature were tested by Begg’s funnel plot and Egger’s test. Results: The pulled data showed that the reduced expression of E-cadherin was significantly associated with overall survival (OS), HR=2.42, 95% CI: 1.50-3.89. The clinical parameters such as lymph node metastasis (LNM), myometrial invasion (MI), International Federation of Gynecology and Obstetrics (FIGO) stage, histological type and pathological type were also significantly associated with reduced expression of E-cadherin. The results of publication biasshowed there were no significant publication bias. Conclusion: Endometrial cancer patients with reduced expression of E-cadherin may have a poorer prognosis than those with normal or higher expression of E-cadherin. PMID:26770483

  17. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Notice requirements for certain pension plan... (CONTINUED) PENSION EXCISE TAXES § 54.4980F-1 Notice requirements for certain pension plan amendments... a plan amendment of an applicable pension plan that significantly reduces the rate of future...

  18. 26 CFR 54.4980F-1 - Notice requirements for certain pension plan amendments significantly reducing the rate of future...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Notice requirements for certain pension plan amendments significantly reducing the rate of future benefit accrual. 54.4980F-1 Section 54.4980F-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES §...

  19. Effortful retrieval reduces hippocampal activity and impairs incidental encoding.

    PubMed

    Reas, Emilie T; Brewer, James B

    2013-05-01

    Functional imaging studies frequently report that the hippocampus is engaged by successful episodic memory retrieval. However, considering that concurrent encoding of the background environment occurs during retrieval and influences medial temporal lobe activity, it is plausible that hippocampal encoding functions are reduced with increased attentional engagement during effortful retrieval. Expanding upon evidence that retrieval efforts suppress activity in hippocampal regions implicated in encoding, this study examines the influence of retrieval effort on encoding performance and the interactive effects of encoding and retrieval on hippocampal and neocortical activity. Functional magnetic resonance imaging was conducted while subjects performed a word recognition task with incidental picture encoding. Both lower memory strength and increased search duration were associated with encoding failure and reduced hippocampal and default network activity. Activity in the anterior hippocampus tracked encoding, which was more strongly deactivated when incidental encoding was unsuccessful. These findings highlight potential contributions from background encoding processes to hippocampal activations during neuroimaging studies of episodic memory retrieval. PMID:23378272

  20. Factors significantly increasing or inhibiting early stages of malignant melanoma (M.M.) and non-invasive evaluation of new treatment by ingestion and external application of optimal doses of the most effective anti-M.M. substances: haritaki, cilantro, vitamin D3, nori, EPA with DHA, & application of special (+) solar energy stored paper, which reduced the M.M. active area & asbestos rapidly.

    PubMed

    Omura, Yoshiaki; Jones, Marilyn; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

    2013-01-01

    Sterilizing the pre-cancer skin of malignant melanoma (M.M.) with 70% Isopropyl alcohol intensified malignancy & the malignant response extended to surrounding normal looking skin, while sterilizing with 80% (vodka) or 12% (plum wine) ethyl alcohol completely inhibited M.M. in the area (both effects lasted for about 90 minutes initially). Burnt food (bread, vegetables, meat, and fish), a variety of smoked & non-smoked fish-skin, many animal's skin, pepper, Vitamin C over 75 mg, mango, pineapple, coconut, almond, sugars, Saccharine & Aspartame, garlic, onion, etc & Electromagnetic field from cellular phones worsened M.M. & induced abnormal M.M. response of surrounding skin. We found the following factors inhibit early stage of M.M. significantly: 1) Increasing normal cell telomere, by taking 500 mg Haritaki, often reached between 400-1150 ng& gradually diminished, but the M.M. response was completely inhibited until normal cell telomeres are reduced to 150 ng, which takes 6-8 hours. More than 70 mg Vitamin C, Orange Juice, & other high Vitamin C containing substances shouldn't be taken because they completely inhibit the effects of Haritaki. 2) We found Chrysotile asbestos & Tremolite asbestos (% of the Chrysotile amount) coexist. A special Cilantro tablet was used to remove asbestos & some toxic metals. 3) Vitamin D3 400 I.U. has a maximum inhibiting effect on M.M. but 800 I.U. or higher promotes malignancy. 4) Noricontaining Iodine, etc., was used. 5) EPA 180 mm with DHA 120 mg was most effectively used after metastasis to the surrounding skin was eliminated. When we combined 1 Cilantro tablet & Vitamin D3 400 I.U. withsmall Nori pieces & EPA with DHA, the effect of complete inhibition of M.M. lasted 9-11 hours. When these anti-M.M.substances (Haritaki, Vitamin D3, Cilantro, Nori, EPA. with DHA) were taken together, the effect lasted 12-14 hoursand M.M. involvement in surrounding normal-looking skin disappeared rapidly & original dark brown or black are as

  1. Sox11 Reduces Caspase-6 Cleavage and Activity

    PubMed Central

    Waldron-Roby, Elaine; Hoerauf, Janine; Arbez, Nicolas; Zhu, Shanshan; Kulcsar, Kirsten; Ross, Christopher A.

    2015-01-01

    The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP) family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117–214 and 362–395 within sox11 as well as a nuclear localization signal (NLS) all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11. PMID:26505998

  2. Reduced Chitinase Activities in Ant Plants of the Genus Macaranga

    NASA Astrophysics Data System (ADS)

    Heil, Martin; Fiala, Brigitte; Linsenmair, K. Eduard; Boller, Thomas

    Many plant species have evolved mutualistic associations with ants, protecting their host against detrimental influences such as herbivorous insects. Letourneau (1998) reported in the case of Piper that ants defend their plants principally against stem-boring insects and also reduce fungal infections on inflorescences. Macaranga plants that were experimentally deprived of their symbiotic Crematogaster ants suffered heavily from shoot borers and pathogenic fungi (Heil 1998). Here we report that ants seem to reduce fungal infections actively in the obligate myrmecophyte Macarangatriloba (Euphorbiaceae), while ant-free plants can be easily infected. We also found extremely low chitinase activity in Macaranga plants. The plants' own biochemical defense seems to be reduced, and low chitinase activity perhaps may represent a predisposition for the evolution of myrmecophytism. These plants are therefore highly dependent on their ants, which obviously function not only as an antiherbivore defense but also as an effective agent against fungal pathogens.

  3. Tritium retention in reduced-activation ferritic/martensitic steels

    SciTech Connect

    Hatano, Y.; Abe, S.; Matsuyama, M.; Alimov, V.K.; Spitsyn, A.V.; Bobyr, N.P.; Cherkez, D.I.; Khripunov, B.I.; Golubeva, A.V.; Ogorodnikova, O.V.; Klimov, N.S.; Chernov, V.M.; Oyaidzu, M.; Yamanishi, T.

    2015-03-15

    Reduced-activation ferritic/martensitic (RAFM) steels are structural material candidates for breeding blankets of future fusion reactors. Therefore, tritium (T) retention in RAFM steels is an important problem in assessing the T inventory of blankets. In this study, specimens of RAFM steels were subjected to irradiation of 20 MeV W ions to 0.54 displacements per atom (dpa), exposure to high flux D plasmas at 400 and 600 K and that to pulsed heat loads. The specimens thus prepared were exposed to DT gas at 473 K. Despite severe modification in the surface morphology, heat loads had negligible effects on T retention. Significant increase in T retention at the surface and/or subsurface was observed after D plasma exposure. However, T trapped at the surface/subsurface layer was easily removed by maintaining the specimens in the air at about 300 K. Displacement damage led to increase in T retention in the bulk due to the trapping effects of defects, and T trapped was stable at 300 K. It was therefore concluded that displacement damages had the largest influence on T retention under the present conditions.

  4. Overexpression of rice glutaredoxins (OsGrxs) significantly reduces arsenite accumulation by maintaining glutathione pool and modulating aquaporins in yeast.

    PubMed

    Verma, Pankaj Kumar; Verma, Shikha; Meher, Alok Kumar; Pande, Veena; Mallick, Shekhar; Bansiwal, Amit Kumar; Tripathi, Rudra Deo; Dhankher, Om Parkash; Chakrabarty, Debasis

    2016-09-01

    Arsenic (As) is an acute poison and class I carcinogen, can cause a serious health risk. Staple crops like rice are the primary source of As contamination in human food. Rice grown on As contaminated areas accumulates higher As in their edible parts. Based on our previous transcriptome data, two rice glutaredoxins (OsGrx_C7 and OsGrx_C2.1) were identified that showed up-regulated expression during As stress. Here, we report OsGrx_C7 and OsGrx_C2.1 from rice involved in the regulation of intracellular arsenite (AsIII). To elucidate the mechanism of OsGrx mediated As tolerance, both OsGrxs were cloned and expressed in Escherichia coli (Δars) and Saccharomyces cerevisiae mutant strains (Δycf1, Δacr3). The expression of OsGrxs increased As tolerance in E. coli (Δars) mutant strain (up to 4 mM AsV and up to 0.6 mM AsIII). During AsIII exposure, S. cerevisiae (Δacr3) harboring OsGrx_C7 and OsGrx_C2.1 have lower intracellular AsIII accumulation (up to 30.43% and 24.90%, respectively), compared to vector control. Arsenic accumulation in As-sensitive S. cerevisiae mutant (Δycf1) also reduced significantly on exposure to inorganic As. The expression of OsGrxs in yeast maintained intracellular GSH pool and increased extracellular GSH concentration. Purified OsGrxs displays in vitro GSH-disulfide oxidoreductase, glutathione reductase and arsenate reductase activities. Also, both OsGrxs are involved in AsIII extrusion by altering the Fps1 transcripts in yeast and protect the cell by maintaining cellular GSH pool. Thus, our results strongly suggest that OsGrxs play a crucial role in the maintenance of the intracellular GSH pool and redox status of the cell during both AsV and AsIII stress and might be involved in regulating intracellular AsIII levels by modulation of aquaporin expression and functions. PMID:27174139

  5. Using Stable Isotopes to Assess Reduced Physical Activity of Individuals with Prader-Willi Syndrome.

    ERIC Educational Resources Information Center

    Davies, Peter S. W.; Joughlin, C.

    1993-01-01

    This study found that the physical activity levels of 10 children with Prader-Willi syndrome were significantly reduced in comparison to children without the syndrome. Increasing activity levels in children with Prader-Willi syndrome is suggested as a way to raise total energy expenditure and control weight gain. (Author/JDD)

  6. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach

    SciTech Connect

    Cardenas, Erick; Leigh, Mary Beth; Marsh, Terence; Tiedje, James M.; Wu, Wei-min; Luo, Jian; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Criddle, Craig; Carley, Jack M; Carroll, Sue L; Gentry, Terry J; Watson, David B; Gu, Baohua; Jardine, Philip M; Zhou, Jizhong

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 M and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

  7. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    PubMed

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  8. A combined massively parallel sequencing indicator species approach revealed significant association between sulfate-reducing bacteria and uranium-reducing microbial communities

    SciTech Connect

    Cardenas, Erick; Wu, Wei-min; Leigh, Mary Beth; Carley, Jack M; Carroll, Sue L; Gentry, Terry; Luo, Jian; Watson, David B; Gu, Baohua; Ginder-Vogel, Matthew A.; Kitanidis, Peter K.; Jardine, Philip; Kelly, Shelly D; Zhou, Jizhong; Criddle, Craig; Marsh, Terence; Tiedje, James

    2010-08-01

    Massively parallel sequencing has provided a more affordable and high throughput method to study microbial communities, although it has been mostly used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium (VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee, USA. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 {micro}M, and created geochemical gradients in electron donors from the inner loop injection well towards the outer loop and down-gradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical created conditions. Castellaniella, and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity; while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. Abundance of these bacteria as well as the Fe(III)- and U(VI)-reducer Geobacter correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to the electron donor addition and by the groundwater flow path. A false discovery rate approach was implemented to discard false positives by chance given the large amount of data compared.

  9. Recent approaches for reducing hemolytic activity of chemotherapeutic agents.

    PubMed

    Jeswani, Gunjan; Alexander, Amit; Saraf, Shailendra; Saraf, Swarnlata; Qureshi, Azra; Ajazuddin

    2015-08-10

    Drug induced hemolysis is a frequent complication associated with chemotherapy. It results from interaction of drug with erythrocyte membrane and leads to cell lysis. In recent past, various approaches were made to reduce drug-induced hemolysis, which includes drug polymer conjugation, drug delivery via colloidal carriers and hydrogels, co-administration of botanical agents and modification in molecular chemistry of drug molecules. The basic concept behind these strategies is to protect the red blood cells from membrane damaging effects of drugs. There are several examples of drug polymer conjugate that either are approved by Food and Drug Administration or are under clinical trial for delivering drugs with reduced toxicities. Likewise, colloidal carriers are also used successfully nowadays for the delivery of various chemotherapeutic agents like gemcitabine and amphotericin B with remarkable decrease in their hemolytic activity. Similarly, co-administration of botanical agents with drugs works as secondary system proving protection and strength to erythrocyte membranes. In addition to the above statement, interaction hindrance between RBC and drug molecule by molecular modification plays an important role in reducing hemolysis. This review predominantly describes the above recent approaches explored to achieve the reduced hemolytic activity of drugs especially chemotherapeutic agents. PMID:26047758

  10. Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Nie, Chao; Liu, Xiaomin; Feng, Lei; Zhang, Fengyu; Lu, Jiehua; Li, Jianxin; Li, Yang; Tao, Wei; Gregory, Simon G; Gottschalk, William; Lutz, Michael W; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Ming, Qi; Yang, Huanming; Min, Junxia; Willcox, D Craig; Willcox, Bradley J; Gu, Jun; Hauser, Elizabeth; Tian, Xiao-Li; Vaupel, James W

    2016-06-01

    On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs. PMID:26414954

  11. Low-chromium reduced-activation ferritic steels for fusion

    SciTech Connect

    Klueh, R.L.; Alexander, D.J.; Kenik, E.A.

    1996-04-01

    Development of reduced-activation ferritic steels has concentrated on high-chromium (8-10 wt% Cr) steels. However, there are advantages for a low-chromium steel, and initial ORNL studies on reduced-activation steels were on compositions with 2.25 to 12% Cr. Those studies showed an Fe-2.25Cr-2W-0.25V-0.1C (2 1/4Cr-2WV) steel to have the highest strenglth of the steels studied. Although this steel had the best strength, Charpy impact properties were inferior to those of an Fe-9Cr-2W-0.25V-0.07Ta-0.1C (9Cr-2WVTa) and an Fe-2.25Cr-2W-0.1C (2 1/4Cr-2W) steel. Therefore, further development of the low-chromium Cr-W steels was required. These results indicate that it is possible to develop low-chromium reduced-activation ferritic steels that have tensile and impact properties as good or better than those of high-chromium (7-9% Cr) steels. Further improvement of properties should be possible by optimizing the composition.

  12. Trends in space activities in 2014: The significance of the space activities of governments

    NASA Astrophysics Data System (ADS)

    Paikowsky, Deganit; Baram, Gil; Ben-Israel, Isaac

    2016-01-01

    This article addresses the principal events of 2014 in the field of space activities, and extrapolates from them the primary trends that can be identified in governmental space activities. In 2014, global space activities centered on two vectors. The first was geopolitical, and the second relates to the matrix between increasing commercial space activities and traditional governmental space activities. In light of these two vectors, the article outlines and analyzes trends of space exploration, human spaceflights, industry and technology, cooperation versus self-reliance, and space security and sustainability. It also reviews the space activities of the leading space-faring nations.

  13. Oxytocin reduces amygdala activity, increases social interactions, and reduces anxiety-like behavior irrespective of NMDAR antagonism.

    PubMed

    Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E; Siegel, Steven J

    2015-08-01

    Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference. PMID:26214213

  14. Oxytocin reduces amygdala activity, increases social interactions and reduces anxiety-like behavior irrespective of NMDAR antagonism

    PubMed Central

    Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E.; Siegel, Steven J.

    2015-01-01

    Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala leading to increased fear and social anxiety. Several studies have demonstrated the pro-social effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of sub-chronic oxytocin on electroencephalographic (EEG) activity in amygdala of mice during performance of the three chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine, but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, while oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate pro-social and social anxiety pathways may mediate social preference. PMID:26214213

  15. Conformational Preferences Underlying Reduced Activity of a Thermophilic Ribonuclease H

    PubMed Central

    Stafford, Kate A.; Trbovic, Nikola; Butterwick, Joel A.; Abel, Robert; Friesner, Richard A.; Palmer, Arthur G.

    2015-01-01

    The conformational basis for reduced activity of the thermophilic ribonuclease HI enzyme from Thermus thermophilus, compared to its mesophilic homolog from Escherichia coli, is elucidated using a combination of NMR spectroscopy and molecular dynamics (MD) simulations. Explicit-solvent all-atom MD simulations of the two wild-type proteins and an E. coli mutant in which a glycine residue is inserted after position 80 to mimic the T. thermophilus protein reproduce the differences in conformational dynamics determined from 15N spin-relaxation NMR spectroscopy of three loop regions that surround the active site and contain functionally important residues: the glycine-rich region, the handle region, and the β5/αE loop. Examination of the MD trajectories indicates that the thermophilic protein samples conformations productive for substrate binding and activity less frequently than the mesophilic enzyme, although these differences may manifest as either increased or decreased relative flexibility of the different regions. Additional MD simulations indicate that mutations increasing activity of the T. thermophilus enzyme at mesophilic temperatures do so by reconfiguring the local environments of the mutated sites to more closely resemble active conformations. Taken together, the results show that both locally increased and decreased flexibility contribute to an overall reduction in activity of T. thermophilus ribonuclease H compared to its mesophilic E. coli homolog. PMID:25550198

  16. American ginseng significantly reduced the progression of high-fat-diet-enhanced colon carcinogenesis in ApcMin/+mice

    PubMed Central

    Yu, Chunhao; Wen, Xiao-Dong; Zhang, Zhiyu; Zhang, Chun-Feng; Wu, Xiaohui; He, Xin; Liao, Yang; Wu, Ningning; Wang, Chong-Zhi; Du, Wei; He, Tong-Chuan; Yuan, Chun-Su

    2015-01-01

    Background Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods A genetically engineered ApcMin/+ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results After oral ginseng administration (10–20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, IL-6, tumor necrosis factor-α, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention. PMID:26199554

  17. Bacteriophage cocktail significantly reduces or eliminates Listeria monocytogenes contamination on lettuce, apples, cheese, smoked salmon and frozen foods.

    PubMed

    Perera, Meenu N; Abuladze, Tamar; Li, Manrong; Woolston, Joelle; Sulakvelidze, Alexander

    2015-12-01

    ListShield™, a commercially available bacteriophage cocktail that specifically targets Listeria monocytogenes, was evaluated as a bio-control agent for L. monocytogenes in various Ready-To-Eat foods. ListShield™ treatment of experimentally contaminated lettuce, cheese, smoked salmon, and frozen entrèes significantly reduced (p < 0.05) L. monocytogenes contamination by 91% (1.1 log), 82% (0.7 log), 90% (1.0 log), and 99% (2.2 log), respectively. ListShield™ application, alone or combined with an antioxidant/anti-browning solution, resulted in a statistically significant (p < 0.001) 93% (1.1 log) reduction of L. monocytogenes contamination on apple slices after 24 h at 4 °C. Treatment of smoked salmon from a commercial processing facility with ListShield™ eliminated L. monocytogenes (no detectable L. monocytogenes) in both the naturally contaminated and experimentally contaminated salmon fillets. The organoleptic quality of foods was not affected by application of ListShield™, as no differences in the color, taste, or appearance were detectable. Bio-control of L. monocytogenes with lytic bacteriophage preparations such as ListShield™ can offer an environmentally-friendly, green approach for reducing the risk of listeriosis associated with the consumption of various foods that may be contaminated with L. monocytogenes. PMID:26338115

  18. Photosynthetic electron sinks in transgenic tobacco with reduced amounts of Rubisco: little evidence for significant Mehler reaction.

    PubMed

    Ruuska, S A; Badger, M R; Andrews, T J; von Caemmerer, S

    2000-02-01

    Transgenic tobacco (Nicotiana tabacum L. cv. W38) plants with an antisense gene directed against the mRNA of the small subunit of Rubisco were used to investigate the role of O2 as an electron acceptor during photosynthesis. The reduction in Rubisco has reduced the capacity for CO2-fixation in these plants without a similar reduction in electron transport capacity. Concurrent measurements of chlorophyll fluorescence and CO2 assimilation at different CO2 and O2 partial pressures showed close linear relationships between chloroplast electron transport rates calculated from chlorophyll fluorescence and those calculated from CO2-fixation. These relationships were similar for wild-type and transgenic plants, indicating that the reduced capacity for CO2 fixation in the transgenic plants did not result in extra electron transport not associated with the photosynthetic carbon reduction (PCR) or photorespiratory carbon oxidation (PCO) cycle. This was further investigated with mass spectrometric measurements of 16O2 and 18O2 exchange made concurrently with measurements of chlorophyll fluorescence. In all tobacco lines the rates of 18O2 uptake in the dark were similar to the 18O2 uptake rates at very high CO2 partial pressures in the light. Rates of oxygenase activity calculated from 18O2 uptake at the compensation point were linearly related to the Rubisco content of leaves. The ratios of oxygenase to carboxylase rates were calculated from measurements of 16O2 evolution and 18O2 uptake at the compensation point. These ratios were lower in the transgenic plants, consistent with their higher CO2 compensation points. It is concluded that although there may be some electron transport to O2 to balance conflicting demands of NADPH to ATP requirements, this flux must decrease in proportion with the reduced demand for ATP and NADPH consumption in the transgenic lines. The altered balance between electron transport and Rubisco capacity, however, does not result in rampant electron

  19. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

    PubMed Central

    Berbée, Jimmy F. P.; Boon, Mariëtte R; Khedoe, P. Padmini S. J.; Bartelt, Alexander; Schlein, Christian; Worthmann, Anna; Kooijman, Sander; Hoeke, Geerte; Mol, Isabel M.; John, Clara; Jung, Caroline; Vazirpanah, Nadia; Brouwers, Linda P.J.; Gordts, Philip L.S.M.; Esko, Jeffrey D.; Hiemstra, Pieter S.; Havekes, Louis M.; Scheja, Ludger; Heeren, Joerg; Rensen, Patrick C.N.

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe−/− and Ldlr−/− mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe−/− and Ldlr−/− mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis. PMID:25754609

  20. Combined effect of lime (Citrus aurantitolia) and drying on reducing bacteria of public health significance in Edible Oyster (Crassostrea madrasensis).

    PubMed

    Hassan, Femeena; Geethalakshmi, V; Jeeva, J Charles; Babu, M Remya

    2013-02-01

    Combined effect of lime and drying on bacteria of public health significance in Edible Oyster (Crassostrea madrasensis) from Munambam coastal belt (Kerala, India) were studied (without depuration). Samples were examined for Total Plate Count (TPC), Staphylococcus aureus (hygiene indicator), Total coliforms, Faecal coliforms, Escherichia coli, (faecal indicator) Faecal Streptococci (faecal indicator), Salmonella, Vibrio cholera and Listeria monocytogenes. The fresh oyster meat though did not confirm to the specifications laid by National shellfish sanitation programme (NSSP), after treatment with lime with and without drying found to show significant reduction in counts and meet the required standards. Prevalence of faecal indicators in the fresh sample indicated faecal pollution in the area. The isolation of potentially pathogenic bacteria, V. parahaemolyticus in fresh sample indicates high risk of people consuming and handling oysters in raw and semi processed form and also it may lead to cross contamination. The present study indicates that treatment with natural organic product like lime and simple preservation technique, drying can effectively reduce the bacterial load. The study also revealed that TPC of water and soil collected from the site from where oysters were collected was less than from the meat. PMID:24425910

  1. Hydrogenase activity in aged, nonviable Desulfovibrio vulgaris cultures and its significance in anaerobic biocorrosion

    SciTech Connect

    Chatelus, C.; Carrier, P.; Saignes, P.; Libert, M.F.; Berlier, Y.; Lespinat, P.A.; Fauque, G.; Legall, J.

    1987-07-01

    Batch cultures of Desulfovibrio vulgaris stored at 32 degrees C for 10 months have been found to retain 50% of the hydrogenase activity of a 1-day culture. The hydrogenase found in old cultures needs reducing conditions for its activation. Viable cell counts are negative after 6 months, showing that the hydrogenase activity does not depend on the presence of viable cells. These observations are of importance in the understanding of anaerobic biocorrosion of metals caused by depolarization phenomena. (Refs. 16).

  2. Designation of alloy composition of reduced-activation martensitic steel

    NASA Astrophysics Data System (ADS)

    Kimura, A.; Kayano, H.; Misawa, T.; Matsui, H.

    1994-09-01

    An alloy composition of reduced-activation martensitic steel for fusion reactor is designed on the basis of the experimental results of postirradiation microstructure, mechanical properties, such as creep, fracture toughness and tensile properties, hydrogen effects and corrosion. At present, a desired composition of the steel is 0.1C-0.05Si-0.5Mn-9Cr-2W-0.25V-0.02Ti-0.05Ta- < 0.002S- < 0.002P by weight percent. Effects of the other minor elements such as Al, Zr and B are also inspected. An addition of 0.05 wt% Ta increases the high temperature strength but reduces the fracture toughness. Susceptibility to hydrogen-induced cracking is reduced by an addition of 0.03 wt% Al, though it results in a severe degradation of the fracture toughness. An addition of 30 wppm B together with the addition of 0.02 wt% Ti increases the fracture toughness. Void nucleation at grain boundaries, however, is enhanced by the B addition under the FFTF irradiation at 638 K in 10 dpa.

  3. Active fans and grizzly bears: Reducing risks for wilderness campers

    NASA Astrophysics Data System (ADS)

    Sakals, M. E.; Wilford, D. J.; Wellwood, D. W.; MacDougall, S. A.

    2010-03-01

    Active geomorphic fans experience debris flows, debris floods and/or floods (hydrogeomorphic processes) that can be hazards to humans. Grizzly bears ( Ursus arctos) can also be a hazard to humans. This paper presents the results of a cross-disciplinary study that analyzed both hydrogeomorphic and grizzly bear hazards to wilderness campers on geomorphic fans along a popular hiking trail in Kluane National Park and Reserve in southwestern Yukon Territory, Canada. Based on the results, a method is proposed to reduce the risks to campers associated with camping on fans. The method includes both landscape and site scales and is based on easily understood and readily available information regarding weather, vegetation, stream bank conditions, and bear ecology and behaviour. Educating wilderness campers and providing a method of decision-making to reduce risk supports Parks Canada's public safety program; a program based on the principle of user self-sufficiency. Reducing grizzly bear-human conflicts complements the efforts of Parks Canada to ensure a healthy grizzly bear population.

  4. Electrographic seizures are significantly reduced by in vivo inhibition of neuronal uptake of extracellular glutamine in rat hippocampus

    PubMed Central

    Kanamori, Keiko; Ross, Brian D.

    2013-01-01

    Summary Rats were given unilateral kainate injection into hippocampal CA3 region, and the effect of chronic electrographic seizures on extracellular glutamine (GLNECF) was examined in those with low and steady levels of extracellular glutamate (GLUECF). GLNECF, collected by microdialysis in awake rats for 5 h, decreased to 62 ± 4.4% of the initial concentration (n = 6). This change correlated with the frequency and magnitude of seizure activity, and occurred in the ipsilateral but not in contralateral hippocampus, nor in kainate-injected rats that did not undergo seizure (n = 6). Hippocampal intracellular GLN did not differ between the Seizure and No-Seizure Groups. These results suggested an intriguing possibility that seizure-induced decrease of GLNECF reflects not decreased GLN efflux into the extracellular fluid, but increased uptake into neurons. To examine this possibility, neuronal uptake of GLNECF was inhibited in vivo by intrahippocampal perfusion of 2-(methylamino)isobutyrate, a competitive and reversible inhibitor of the sodium-coupled neutral amino acid transporter (SNAT) subtypes 1 and 2, as demonstrated by 1.8 ± 0.17 fold elevation of GLNECF (n = 7). The frequency of electrographic seizures during uptake inhibition was reduced to 35 ± 7% (n = 7) of the frequency in pre-perfusion period, and returned to 88 ± 9% in the post-perfusion period. These novel in vivo results strongly suggest that, in this well-established animal model of temporal-lobe epilepsy, the observed seizure-induced decrease of GLNECF reflects its increased uptake into neurons to sustain enhanced glutamatergic epileptiform activity, thereby demonstrating a possible new target for anti-seizure therapies. PMID:24070846

  5. Meditation leads to reduced default mode network activity beyond an active task.

    PubMed

    Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2015-09-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task. PMID:25904238

  6. Meditation leads to reduced default mode network activity beyond an active task

    PubMed Central

    Garrison, Kathleen A.; Zeffiro, Thomas A.; Scheinost, Dustin; Constable, R. Todd; Brewer, Judson A.

    2015-01-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest despite other studies reporting differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, this study compared meditation to another active cognitive task, both to replicate findings that meditation is associated with relatively reduced default mode network activity, and to extend these findings by testing whether default mode activity was reduced during meditation beyond the typical reductions observed during effortful tasks. In addition, prior studies have used small groups, whereas the current study tested these hypotheses in a larger group. Results indicate that meditation is associated with reduced activations in the default mode network relative to an active task in meditators compared to controls. Regions of the default mode showing a group by task interaction include the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that suppression of default mode processing may represent a central neural process in long-term meditation, and suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task. PMID:25904238

  7. A commercial PCV2a-based vaccine significantly reduces PCV2b transmission in experimental conditions.

    PubMed

    Rose, N; Andraud, M; Bigault, L; Jestin, A; Grasland, B

    2016-07-19

    Transmission characteristics of PCV2 have been compared between vaccinated and non-vaccinated pigs in experimental conditions. Twenty-four Specific Pathogen Free (SPF) piglets, vaccinated against PCV2 at 3weeks of age (PCV2a recombinant CAP protein-based vaccine), were inoculated at 15days post-vaccination with a PCV2b inoculum (6⋅10(5) TCID50), and put in contact with 24 vaccinated SPF piglets during 42days post-inoculation. Those piglets were shared in six replicates of a contact trial involving 4 inoculated piglets mingled with 4 susceptible SPF piglets. Two replicates of a similar contact trial were made with non-vaccinated pigs. Non vaccinated animals received a placebo at vaccination time and were inoculated the same way and at the same time as the vaccinated group. All the animals were monitored twice weekly using quantitative real-time PCR and ELISA for serology until 42days post-inoculation. The frequency of infection and the PCV2 genome load in sera of the vaccinated pigs were significantly reduced compared to the non-vaccinated animals. The duration of infectiousness was significantly different between vaccinated and non-vaccinated groups (16.6days [14.7;18.4] and 26.6days [22.9;30.4] respectively). The transmission rate was also considerably decreased in vaccinated pigs (β=0.09 [0.05-0.14] compared to β=0.19 [0.11-0.32] in non-vaccinated pigs). This led to an estimated reproduction ratio of 1.5 [95% CI 0.8 - 2.2] in vaccinated animals versus 5.1 [95% CI 2.5 - 8.2] in non-vaccinated pigs when merging data of this experiment with previous trials carried out in same conditions. PMID:27318416

  8. Community-based tsetse fly control significantly reduces fly density and trypanosomosis prevalence in Metekel Zone, Northwest, Ethiopia.

    PubMed

    Girmay, Gebrerufael; Arega, Bezna; Tesfaye, Dawit; Berkvens, Dirk; Muleta, Gadisa; Asefa, Getnet

    2016-03-01

    African animal trypanosomosis is a great obstacle to livestock production where tsetse flies play a major role. Metekel zone is among the tsetse-infested areas. Community-based tsetse fly and trypanosomosis control using targets was conducted from June 2011 to May 2012 in Metekel zone, Ethiopia, to decrease trypanosomosis and tsetse fly. Cloth screen targets were developed, impregnated with 0.1 % deltamethrin, and deployed alongside rivers by the research team together with the community animal health workers. Monthly parasitological and entomological data were collected, processed, and compared with similar data collected before control. Overall average tsetse fly (Glossina tachinoides) density decreased from 1.13 to 0.18 fly/trap/day after control. The density was decreased in all sites with no significant difference among the sites. However, higher decrements were observed in the dry and late dry seasons by more than 12 and 6 times, respectively. The reduction in overall apparent prevalence of trypanosomosis caused by Trypanosoma congolense, Trypanosoma brucei, and Trypanosoma vivax from 12.14 % before to 3.61 % after control coincides with the tsetse fly reduction. In all the study sites, significant reduction was observed before and after control. The highest decrement was observed in the late dry season when the apparent prevalence was reduced from 7.89 to 1.17 % before and after control, respectively. As this approach is simple, cost-effective, and appropriate for riverine tsetse species, we recommend to be scaled up to other similar places. PMID:26885985

  9. Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression.

    PubMed

    Lintas, C; Sacco, R; Garbett, K; Mirnics, K; Militerni, R; Bravaccio, C; Curatolo, P; Manzi, B; Schneider, C; Melmed, R; Elia, M; Pascucci, T; Puglisi-Allegra, S; Reichelt, K-L; Persico, A M

    2009-07-01

    Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 simplex and 5 multiplex families, and a postmortem study of PRKCB1 gene expression in temporocortical gray matter (BA41/42) of 11 autistic patients and controls. PRKCB1 gene haplotypes are significantly associated with autism (P<0.05) and have the autistic endophenotype of enhanced oligopeptiduria (P<0.05). Temporocortical PRKCB1 gene expression was reduced on average by 35 and 31% for the PRKCB1-1 and PRKCB1-2 isoforms (P<0.01 and <0.05, respectively) according to qPCR. Protein amounts measured for the PKCbetaII isoform were similarly decreased by 35% (P=0.05). Decreased gene expression characterized patients carrying the 'normal' PRKCB1 alleles, whereas patients homozygous for the autism-associated alleles displayed mRNA levels comparable to those of controls. Whole genome expression analysis unveiled a partial disruption in the coordinated expression of PKCbeta-driven genes, including several cytokines. These results confirm the association between autism and PRKCB1 gene variants, point toward PKCbeta roles in altered epithelial permeability, demonstrate a significant downregulation of brain PRKCB1 gene expression in autism and suggest that it could represent a compensatory adjustment aimed at limiting an ongoing dysreactive immune process. Altogether, these data underscore potential PKCbeta roles in autism pathogenesis and spur interest in the identification and functional characterization of PRKCB1 gene variants conferring autism vulnerability. PMID:18317465

  10. Reduced mitochondrial and ascorbate-glutathione activity after artificial ageing in soybean seed.

    PubMed

    Xin, Xia; Tian, Qian; Yin, Guangkun; Chen, Xiaoling; Zhang, Jinmei; Ng, Sophia; Lu, Xinxiong

    2014-01-15

    The effect of artificial ageing on the relationship between mitochondrial activities and the antioxidant system was studied in soybean seeds (Glycine max L. cv. Zhongdou No. 27). Ageing seeds for 18d and 41d at 40°C reduced germination from 99% to 52% and 0%, respectively. In comparison to the control, malondialdehyde content and leachate conductivity in aged seeds increased and were associated with membrane damage. Transmission electron microscopy and Percoll density gradient centrifugation showed that aged seeds mainly contained poorly developed mitochondria in which respiration and marker enzymes activities were significantly reduced. Heavy mitochondria isolated from the interface of the 21% and 40% Percoll were analyzed. Mitochondrial antioxidant enzymes activities including superoxide dismutase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase, and dehydroascorbate reductase were significantly reduced in aged seeds. A decrease in total ascorbic acid (ASC) and glutathione (GSH) content as well as the reduced/oxidized ratio of ASC and GSH in mitochondria with prolonged ageing showed that artificial ageing reduced ASC-GSH cycle activity. These results suggested an elevated reactive oxygen species (ROS) level in the aged seeds, which was confirmed by measurements of superoxide radical and hydrogen peroxide levels. We conclude that mitochondrial dysfunction in artificially aged seeds is due to retarded mitochondrial and ASC-GSH cycle activity and elevated ROS accumulation. PMID:24331429

  11. Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption.

    PubMed

    Vengeliene, Valentina; Noori, Hamid R; Spanagel, Rainer

    2015-12-01

    Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effects on alcohol consumption. We conclude that targeting the melatonergic system in alcohol-dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behavior. PMID:25994077

  12. Sensory stimuli reduce the dimensionality of cortical activity

    NASA Astrophysics Data System (ADS)

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    Neural ensembles in alert animals generate complex patterns of activity. Although cortical activity unfolds in a space whose dimension is equal to the number of neurons, it is often restricted to a lower dimensional subspace. Dimensionality is the minimal number of dimensions that accurately capture neural dynamics, and may be related to the computational tasks supported by the neural circuit. Here, we investigate the dimensionality of neural ensembles from the insular cortex of alert rats during periods of `ongoing' (spontaneous) and stimulus-evoked activity. We find that the dimensionality grows with ensemble size, and does so significantly faster during ongoing compared to evoked activity. We explain both results using a recurrent spiking network with clustered architecture, and obtain analytical results on the dependence of dimensionality on ensemble size, number of clusters, and pair-wise noise correlations. The theory predicts a characteristic scaling with ensemble size and the existence of an upper bound on dimensionality, which grows with the number of clusters and decreases with the amount of noise correlations. To our knowledge, this is the first mechanistic model of neural dimensionality in cortex during both spontaneous and evoked activity.

  13. A novel magnetic countertraction device for endoscopic submucosal dissection significantly reduces procedure time and minimizes technical difficulty

    PubMed Central

    Aihara, Hiroyuki; Ryou, Marvin; Kumar, Nitin; Ryan, Michele B.; Thompson, Christopher C.

    2016-01-01

    Background and study aims In endoscopic submucosal dissection (ESD), effective countertraction may overcome the current drawbacks of longer procedure times and increased technical demands. The objective of this study was to compare the efficacy of ESD using a novel magnetic countertraction device with that of the traditional technique. Methods Each ESD was performed on simulated gastric lesions of 30mm diameter created at five different locations. In total, 10 ESDs were performed using this novel device and 10 were performed by the standard technique. Results The magnetic countertraction device allowed directional tissue manipulation and exposure of the submucosal space. The total procedure time was 605 ± 303.7 seconds in the countertraction group vs. 1082 ± 515.9 seconds in the control group (P=0.021). Conclusions This study demonstrated that using a novel magnetic countertraction device during ESD is technically feasible and enables the operator to dynamically manipulate countertraction such that the submucosal layer is visualized directly. Use of this device significantly reduced procedure time compared with conventional ESD techniques. PMID:24573770

  14. Optical trapping of nanoparticles with significantly reduced laser powers by using counter-propagating beams (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Zhao, Chenglong; LeBrun, Thomas W.

    2015-08-01

    Gold nanoparticles (GNP) have wide applications ranging from nanoscale heating to cancer therapy and biological sensing. Optical trapping of GNPs as small as 18 nm has been successfully achieved with laser power as high as 855 mW, but such high powers can damage trapped particles (particularly biological systems) as well heat the fluid, thereby destabilizing the trap. In this article, we show that counter propagating beams (CPB) can successfully trap GNP with laser powers reduced by a factor of 50 compared to that with a single beam. The trapping position of a GNP inside a counter-propagating trap can be easily modulated by either changing the relative power or position of the two beams. Furthermore, we find that under our conditions while a single-beam most stably traps a single particle, the counter-propagating beam can more easily trap multiple particles. This (CPB) trap is compatible with the feedback control system we recently demonstrated to increase the trapping lifetimes of nanoparticles by more than an order of magnitude. Thus, we believe that the future development of advanced trapping techniques combining counter-propagating traps together with control systems should significantly extend the capabilities of optical manipulation of nanoparticles for prototyping and testing 3D nanodevices and bio-sensing.

  15. PARP1 Val762Ala polymorphism reduces enzymatic activity

    SciTech Connect

    Wang Xiaogan; Wang Zhaoqi; Tong Weimin . E-mail: tong@iarc.fr; Shen Yan

    2007-03-02

    Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K {sub m} of PARP1-Ala762 was increased to a 1.2-fold of the K {sub m} of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K {sub m}. This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism.

  16. C5aR-antagonist significantly reduces the deleterious effect of a blunt chest trauma on fracture healing.

    PubMed

    Recknagel, Stefan; Bindl, Ronny; Kurz, Julian; Wehner, Tim; Schoengraf, Philipp; Ehrnthaller, Christian; Qu, Hongchang; Gebhard, Florian; Huber-Lang, Markus; Lambris, John D; Claes, Lutz; Ignatius, Anita

    2012-04-01

    Confirming clinical evidence, we recently demonstrated that a blunt chest trauma considerably impaired fracture healing in rats, possibly via the interaction of posttraumatic systemic inflammation with local healing processes, the underlying mechanisms being unknown. An important trigger of systemic inflammation is the complement system, with the potent anaphylatoxin C5a. Therefore, we investigated whether the impairment of fracture healing by a severe trauma resulted from systemically activated complement. Rats received a blunt chest trauma and a femur osteotomy stabilized with an external fixator. To inhibit the C5a-dependent posttraumatic systemic inflammation, half of the rats received a C5aR-antagonist intravenously immediately and 12 h after the thoracic trauma. Compared to the controls (control peptide), the treatment with the C5aR-antagonist led to a significantly increased flexural rigidity (three-point-bending test), an improved bony bridging of the fracture gap, and a slightly larger and qualitatively improved callus (µCT, histomorphometry) after 35 days. In conclusion, immunomodulation by a C5aR-antagonist could abolish the deleterious effects of a thoracic trauma on fracture healing, possibly by influencing the function of inflammatory and bone cells locally at the fracture site. C5a could possibly represent a target to prevent delayed bone healing in patients with severe trauma. PMID:21922535

  17. SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells

    PubMed Central

    Khan, Reas S.; Fonseca-Kelly, Zoe; Callinan, Catherine; Zuo, Ling; Sachdeva, Mira M.; Shindler, Kenneth S.

    2012-01-01

    Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators reduce oxidative stress and promote mitochondrial function in neuronal cells. Oxidative stress, marked by reactive oxygen species (ROS) accumulation, was induced in RGC-5 cells by serum deprivation, or addition of doxorubicin or hydrogen peroxide, and resulted in significant cell loss. SIRT1 activators resveratrol (RSV) and SRTAW04 reduced ROS levels and promoted cell survival in RGC-5 cells as well as primary RGC cultures. Effects were blocked by SIRT1 siRNA. SIRT1 activators also increased expression of succinate dehydrogenase (SDH), a mitochondrial enzyme, and promoted deacetylation of PGC-1α, a co-enzyme involved in mitochondrial function. Results show SIRT1 activators prevent cell loss by reducing oxidative stress and promoting mitochondrial function in a neuronal cell line. Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress. PMID:23293585

  18. Future role and significance of space activities in reflection of global social, technological and economic trends

    NASA Astrophysics Data System (ADS)

    Diekmann, Andreas; Richarz, Hans.-Peter

    The paper describes the interrelation of space activities and global socio-economic trends like "globalisation of markets" and "renaissance of fine arts". The interrelation reveals the economic strategic, technological and scientific dimension of space activities and their benefits to mankind. Then, the significance and perspectives of space activities in these dimensions are examined in more detail. The paper calls (1) for a more visible initiative to employ space activities to tackle urgent questions of global change and development, and (2) for a stronger impetus to secure European economic position in space sector as a key industry of the 21st century.

  19. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    PubMed Central

    Oguntibeju, Oluwafemi O.; Meyer, Samantha; Aboua, Yapo G.; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID:27403200

  20. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats.

    PubMed

    Oguntibeju, Oluwafemi O; Meyer, Samantha; Aboua, Yapo G; Goboza, Mediline

    2016-01-01

    Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue. PMID:27403200

  1. TriCalm® hydrogel is significantly superior to 2% diphenhydramine and 1% hydrocortisone in reducing the peak intensity, duration, and overall magnitude of cowhage-induced itch

    PubMed Central

    Papoiu, Alexandru DP; Chaudhry, Hunza; Hayes, Erin C; Chan, Yiong-Huak; Herbst, Kenneth D

    2015-01-01

    Background Itch is one of the most frequent skin complaints and its treatment is challenging. From a neurophysiological perspective, two distinct peripheral and spinothalamic pathways have been described for itch transmission: a histaminergic pathway and a nonhistaminergic pathway mediated by protease-activated receptors (PAR)2 and 4. The nonhistaminergic itch pathway can be activated exogenously by spicules of cowhage, a tropical plant that releases a cysteine protease named mucunain that binds to and activates PAR2 and PAR4. Purpose This study was conducted to assess the antipruritic effect of a novel over-the-counter (OTC) steroid-free topical hydrogel formulation, TriCalm®, in reducing itch intensity and duration, when itch was induced with cowhage, and compared it with two other commonly used OTC anti-itch drugs. Study participants and methods This double-blinded, vehicle-controlled, randomized, crossover study recorded itch intensity and duration in 48 healthy subjects before and after skin treatment with TriCalm hydrogel, 2% diphenhydramine, 1% hydrocortisone, and hydrogel vehicle, used as a vehicle control. Results TriCalm hydrogel significantly reduced the peak intensity and duration of cowhage-induced itch when compared to the control itch curve, and was significantly superior to the two other OTC antipruritic agents and its own vehicle in antipruritic effect. TriCalm hydrogel was eight times more effective than 1% hydrocortisone and almost six times more effective than 2% diphenhydramine in antipruritic action, as evaluated by the reduction of area under the curve. Conclusion TriCalm hydrogel has a robust antipruritic effect against nonhistaminergic pruritus induced via the PAR2 pathway, and therefore it could represent a promising treatment option for itch. PMID:25941445

  2. Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis.

    PubMed

    Li, Naisi; Yang, Qiyuan; Walker, Ryan G; Thompson, Thomas B; Du, Min; Rodgers, Buel D

    2016-01-01

    A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle. PMID:26580671

  3. Evaluation of in vitro urease and lipoxygenase inhibition activity of weight reducing tablets.

    PubMed

    Jaffary, Syed Rashid Ali; Ahmed, Syed Waseemuddin; Shakeel, Sadia; Asif, Hafiz Muhammad; Usmanghani, Khan

    2016-07-01

    Enzyme inhibition is a significant part of research in pharmaceutical field in view of the fact that these studies have directed to the innovations of drugs having remarkable performance in diverse physiological conditions. The present study was aimed to assess urease and lipoxygenase inhibitory activity of weight reducing tablets. For evaluating the urease activity indophenol method was employed using Thiourea as the model urease inhibitor. The lipoxygenase inhibition was evaluated by measuring the hydroperoxides produced in lipoxygenation reaction using a purified lipoxygenase with lionoleic acid as substrate. When formulation of the weight reducing tablets was compared at various concentrations (50, 100 and 500µg/ml). The antiurease activity and lipoxygenase inhibition activity increased in a dose dependent manner. The formulations under test have an excellent antiurease and lipoxygenase inhibition potential and prospective to be used in the cure of a variety of complications associated with the production of urease and lipoxygenase enzymes. PMID:27592490

  4. Paraoxonase-1 activity determination via paraoxon substrate yields no significant difference in mild hyperhomocysteinemia.

    PubMed

    Türkeli, Hatice; Caycı, Tuncer; Akgül, Emin Özgür; Macit, Enis; Yaman, Halil; Aydın, Ibrahim; Demirin, Hilmi; Alacam, Hasan; Ozkan, Esin; Cakır, Erdinç; Deren, Ozgür; Erbil, Mehmet Kemal; Kunak, Z Ilker; Burat, Kutlay; Akman, Serif

    2010-11-01

    Elevated plasma homocystein (Hcy) level has been recognized as an important risk factor for a number of cardiovascular diseases, peripheral arterial occlusive disease and venous thrombosis. A part of Hcy in the organism is turned to homocysteine thiolactone (HcyT) via a ring closure reaction, which gains rate in hyperhomocysteinemia, and in turn undergoes a hydrolytic reaction back to Hcy by paraoxonase enzyme (PON). Since this is a protective reflex action enzyme against hyperhomocysteinemia, we investigated how a mild hyperhomocysteinemic nutritional habit affected serum PON activity in a population-based study. The difference detected via enzymatic activity using the paraoxon substrate was statistically non-significant (p=0.19), suggesting a defective performance to reflect the expected significance. Determination of serum PON activity via substrate paraoxon yielded no significant difference in an acute mild hyperhomocysteinemic diet model in humans. PMID:19419786

  5. Mobile Phone Interventions to Increase Physical Activity and Reduce Weight

    PubMed Central

    Stephens, Janna; Allen, Jerilyn

    2013-01-01

    Objective This systematic review was conducted to determine user satisfaction and effectiveness of smartphone applications and text messaging interventions to promote weight reduction and physical activity. Methods Studies of smartphone applications and text messaging interventions related to the cardiovascular risk factors of physical inactivity and overweight/obesity published between January 2005 and August 2010 were eligible. Studies related to disease management were excluded. Study characteristics and results were gathered and synthesized. Results A total of 36 citations from CINAHL, EMBASE, MEDLINE, PsyclNFO, and PubMed were identified; 7 articles were eligible for inclusion. The most frequent outcome measured in the studies was change in the weight of participants (57%). More than half of the studies (71%) reported statistically significant results in at least 1 outcome of weight loss, physical activity, dietary intake, decreased body mass index, decreased waist circumference, sugar-sweetened beverage intake, screen time, and satisfaction or acceptability outcomes. Conclusions All of the technology interventions that were supported by education or an additional intervention demonstrated a beneficial impact of text messaging or smartphone application for reduction of physical inactivity and/or overweight/obesity. More rigorous trials that determine what parts of the technology or intervention are effective as well as establishment of cost-effectiveness are necessary for further evaluation of smartphone and text messaging interventions. PMID:22635061

  6. Barriers associated with reduced physical activity in COPD patients*

    PubMed Central

    Amorim, Priscila Batista; Stelmach, Rafael; Carvalho, Celso Ricardo Fernandes; Fernandes, Frederico Leon Arrabal; Carvalho-Pinto, Regina Maria; Cukier, Alberto

    2014-01-01

    OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. PMID:25410838

  7. Materials design data for reduced activation martensitic steel type EUROFER

    NASA Astrophysics Data System (ADS)

    Tavassoli, A.-A. F.; Alamo, A.; Bedel, L.; Forest, L.; Gentzbittel, J.-M.; Rensman, J.-W.; Diegele, E.; Lindau, R.; Schirra, M.; Schmitt, R.; Schneider, H. C.; Petersen, C.; Lancha, A.-M.; Fernandez, P.; Filacchioni, G.; Maday, M. F.; Mergia, K.; Boukos, N.; Baluc; Spätig, P.; Alves, E.; Lucon, E.

    2004-08-01

    Materials design limits derived so far from the data generated in Europe for the reduced activation ferritic/martensitic (RAFM) steel type Eurofer are presented. These data address the short-term needs of the ITER Test Blanket Modules and a DEMOnstration fusion reactor. Products tested include plates, bars, tubes, TIG and EB welds, as well as powder consolidated blocks and solid-solid HIP joints. Effects of thermal ageing and low dose neutron irradiation are also included. Results are sorted and screened according to design code requirements before being introduced in reference databases. From the physical properties databases, variations of magnetic properties, modulus of elasticity, density, thermal conductivity, thermal diffusivity, specific heat, mean and instantaneous linear coefficients of thermal expansion versus temperature are derived. From the tensile and creep properties databases design allowable stresses are derived. From the instrumented Charpy impact and fracture toughness databases, ductile to brittle transition temperature, toughness and behavior of materials in different fracture modes are evaluated. From the fatigue database, total strain range versus number of cycles to failure curves are plotted and used to derive fatigue design curves. Cyclic curves are also derived and compared with monotonic hardening curves. Finally, irradiated and aged materials data are compared to ensure that the safety margins incorporated in unirradiated design limits are not exceeded.

  8. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

    PubMed Central

    Hubbard-Turner, Tricia; Wikstrom, Erik A.; Guderian, Sophie; Turner, Michael J.

    2015-01-01

    We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J) were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament (ATFL)/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011). Daily duration was different between the three running groups (p = 0.048). The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046) while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028) compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005). The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately. Key points A single ankle significantly decreased physical activity levels in mice across the lifespan. Decreased physical activity could significantly negatively impact overall health if not

  9. Differential responses of nitrate reducer community size, structure, and activity to tillage systems.

    PubMed

    Chèneby, D; Brauman, A; Rabary, B; Philippot, L

    2009-05-01

    The main objective of this study was to determine how the size, structure, and activity of the nitrate reducer community were affected by adoption of a conservative tillage system as an alternative to conventional tillage. The experimental field, established in Madagascar in 1991, consists of plots subjected to conventional tillage or direct-seeding mulch-based cropping systems (DM), both amended with three different fertilization regimes. Comparisons of size, structure, and activity of the nitrate reducer community in samples collected from the top layer in 2005 and 2006 revealed that all characteristics of this functional community were affected by the tillage system, with increased nitrate reduction activity and numbers of nitrate reducers under DM. Nitrate reduction activity was also stimulated by combined organic and mineral fertilization but not by organic fertilization alone. In contrast, both negative and positive effects of combined organic and mineral fertilization on the size of the nitrate reducer community were observed. The size of the nitrate reducer community was a significant predictor of the nitrate reduction rates except in one treatment, which highlighted the inherent complexities in understanding the relationships the between size, diversity, and structure of functional microbial communities along environmental gradients. PMID:19304827

  10. Differential Responses of Nitrate Reducer Community Size, Structure, and Activity to Tillage Systems▿ †

    PubMed Central

    Chèneby, D.; Brauman, A.; Rabary, B.; Philippot, L.

    2009-01-01

    The main objective of this study was to determine how the size, structure, and activity of the nitrate reducer community were affected by adoption of a conservative tillage system as an alternative to conventional tillage. The experimental field, established in Madagascar in 1991, consists of plots subjected to conventional tillage or direct-seeding mulch-based cropping systems (DM), both amended with three different fertilization regimes. Comparisons of size, structure, and activity of the nitrate reducer community in samples collected from the top layer in 2005 and 2006 revealed that all characteristics of this functional community were affected by the tillage system, with increased nitrate reduction activity and numbers of nitrate reducers under DM. Nitrate reduction activity was also stimulated by combined organic and mineral fertilization but not by organic fertilization alone. In contrast, both negative and positive effects of combined organic and mineral fertilization on the size of the nitrate reducer community were observed. The size of the nitrate reducer community was a significant predictor of the nitrate reduction rates except in one treatment, which highlighted the inherent complexities in understanding the relationships the between size, diversity, and structure of functional microbial communities along environmental gradients. PMID:19304827

  11. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    ERIC Educational Resources Information Center

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  12. Subjective Significance Shapes Arousal Effects on Modified Stroop Task Performance: A Duality of Activation Mechanisms Account.

    PubMed

    Imbir, Kamil K

    2016-01-01

    Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance. PMID:26869974

  13. Subjective Significance Shapes Arousal Effects on Modified Stroop Task Performance: A Duality of Activation Mechanisms Account

    PubMed Central

    Imbir, Kamil K.

    2016-01-01

    Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance. PMID:26869974

  14. Defect-induced enhanced photocatalytic activities of reduced α-Fe2O3 nanoblades.

    PubMed

    Feng, Honglei; Wang, Yiqian; Wang, Chao; Diao, Feiyu; Zhu, Wenhui; Mu, Peng; Yuan, Lu; Zhou, Guangwen; Rosei, Federico

    2016-07-22

    Bicrystalline α-Fe2O3 nanoblades (NBs) synthesized by thermal oxidation of iron foils were reduced in vacuum, to study the effect of reduction treatment on microstructural changes and photocatalytic properties. After the vacuum reduction, most bicrystalline α-Fe2O3 NBs transform into single-layered NBs, which contain more defects such as oxygen vacancies, perfect dislocations and dense pores. By comparing the photodegradation capability of non-reduced and reduced α-Fe2O3 NBs over model dye rhodamine B (RhB) in the presence of hydrogen peroxide, we find that vacuum-reduction induced microstructural defects can significantly enhance the photocatalytic efficiency. Even after 10 cycles, the reduced α-Fe2O3 NBs still show a very high photocatalytic activity. Our results demonstrate that defect engineering is a powerful tool to enhance the photocatalytic performance of nanomaterials. PMID:27285480

  15. Defect-induced enhanced photocatalytic activities of reduced α-Fe2O3 nanoblades

    NASA Astrophysics Data System (ADS)

    Feng, Honglei; Wang, Yiqian; Wang, Chao; Diao, Feiyu; Zhu, Wenhui; Mu, Peng; Yuan, Lu; Zhou, Guangwen; Rosei, Federico

    2016-07-01

    Bicrystalline α-Fe2O3 nanoblades (NBs) synthesized by thermal oxidation of iron foils were reduced in vacuum, to study the effect of reduction treatment on microstructural changes and photocatalytic properties. After the vacuum reduction, most bicrystalline α-Fe2O3 NBs transform into single-layered NBs, which contain more defects such as oxygen vacancies, perfect dislocations and dense pores. By comparing the photodegradation capability of non-reduced and reduced α-Fe2O3 NBs over model dye rhodamine B (RhB) in the presence of hydrogen peroxide, we find that vacuum-reduction induced microstructural defects can significantly enhance the photocatalytic efficiency. Even after 10 cycles, the reduced α-Fe2O3 NBs still show a very high photocatalytic activity. Our results demonstrate that defect engineering is a powerful tool to enhance the photocatalytic performance of nanomaterials.

  16. Protopanaxadiol, an Active Ginseng Metabolite, Significantly Enhances the Effects of Fluorouracil on Colon Cancer

    PubMed Central

    Wang, Chong-Zhi; Zhang, Zhiyu; Wan, Jin-Yi; Zhang, Chun-Feng; Anderson, Samantha; He, Xin; Yu, Chunhao; He, Tong-Chuan; Qi, Lian-Wen; Yuan, Chun-Su

    2015-01-01

    In this study, we evaluated the effects of protopanaxadiol (PPD), a gut microbiome induced ginseng metabolite, in increasing the anticancer effects of a chemotherapeutic agent fluorouracil (5-FU) on colorectal cancer. An in vitro HCT-116 colorectal cancer cell proliferation test was conducted to observe the effects of PPD, 5-FU and their co-administration and the related mechanisms of action. Then, an in vivo xenografted athymic mouse model was used to confirm the in vitro data. Our results showed that the human gut microbiome converted ginsenoside compound K to PPD as a metabolite. PPD and 5-FU significantly inhibited HCT-116 cell proliferation in a concentration-dependent manner (both p < 0.01), and the effects of 5-FU were very significantly enhanced by combined treatment with PPD (p < 0.01). Cell cycle evaluation demonstrated that 5-FU markedly induced the cancer cell S phase arrest, while PPD increased arrest in G1 phase. Compared to the control, 5-FU and PPD increased apoptosis, and their co-administration significantly increased the number of apoptotic cells (p < 0.01). Using bioluminescence imaging, in vivo data revealed that 5-FU significantly reduced the tumor growth up to Day 20 (p < 0.05). PPD and 5-FU co-administration very significantly reduced the tumor size in a dose-related manner (p < 0.01 compared to the 5-FU alone). The quantification of the tumor size and weight changes for 43 days supported the in vivo imaging data. Our results demonstrated that the co-administration of PPD and 5-FU significantly inhibited the tumor growth, indicating that PPD significantly enhanced the anticancer action of 5-FU, a commonly used chemotherapeutic agent. PPD may have a clinical value in 5-FU’s cancer therapeutics. PMID:25625815

  17. Increased water activity reduces the thermal resistance of Salmonella enterica in peanut butter.

    PubMed

    He, Yingshu; Li, Ye; Salazar, Joelle K; Yang, Jingyun; Tortorello, Mary Lou; Zhang, Wei

    2013-08-01

    Increased water activity in peanut butter significantly (P < 0.05) reduced the heat resistance of desiccation-stressed Salmonella enterica serotypes treated at 90 °C. The difference in thermal resistance was less notable when strains were treated at 126 °C. Using scanning electron microscopy, we observed minor morphological changes of S. enterica cells resulting from desiccation and rehydration processes in peanut oil. PMID:23728806

  18. Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11β knock-down.

    PubMed

    Esmaeili, M; Ghaedi, K; Shoaraye Nejati, A; Nematollahi, M; Shiralyian, H; Nasr-Esfahani, M H

    2016-01-15

    Peroxisomes constitute special cellular organelles which display a variety of metabolic functions including fatty acid oxidation and free radical elimination. Abundance of these flexible organelles varies in response to different environmental stimuli. It has been demonstrated that PEX11β, a peroxisomal membrane elongation factor, is involved in the regulation of size, shape and number of peroxisomes. To investigate the role of PEX11β in neural differentiation of mouse embryonic stem cells (mESCs), we generated a stably transduced mESCs line that derives the expression of a short hairpin RNA against Pex11β gene following doxycycline (Dox) induction. Knock-down of Pex11β, during neural differentiation, significantly reduced the expression of neural progenitor cells and mature neuronal markers (p<0.05) indicating that decreased expression of PEX11β suppresses neuronal maturation. Additionally, mRNA levels of other peroxisome-related genes such as PMP70, Pex11α, Catalase, Pex19 and Pex5 were also significantly reduced by Pex11β knock-down (p<0.05). Interestingly, pretreatment of transduced mESCs with peroxisome proliferator-activated receptor γ agonist (pioglitazone (Pio)) ameliorated the inhibitory effects of Pex11β knock down on neural differentiation. Pio also significantly (p<0.05) increased the expression of neural progenitor and mature neuronal markers besides the expression of peroxisomal genes in transduced mESC. Results elucidated the importance of Pex11β expression in neural differentiation of mESCs, thereby highlighting the essential role of peroxisomes in mammalian neural differentiation. The observation that Pio recovered peroxisomal function and improved neural differentiation of Pex11β knocked-down mESCs, proposes a potential new pharmacological implication of Pio for neurogenesis in patients with peroxisomal defects. PMID:26562432

  19. Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice.

    PubMed

    Magdalon, Juliana; Chimin, Patricia; Belchior, Thiago; Neves, Rodrigo X; Vieira-Lara, Marcel A; Andrade, Maynara L; Farias, Talita S; Bolsoni-Lopes, Andressa; Paschoal, Vivian A; Yamashita, Alex S; Kowaltowski, Alicia J; Festuccia, William T

    2016-05-01

    Mechanistic target of rapamycin complex 1 (mTORC1) loss of function reduces adiposity whereas partial mTORC1 inhibition enhances fat deposition. Herein we evaluated how constitutive mTORC1 activation in adipocytes modulates adiposity in vivo. Mice with constitutive mTORC1 activation in adipocytes induced by tuberous sclerosis complex (Tsc)1 deletion and littermate controls were evaluated for body mass, energy expenditure, glucose and fatty acid metabolism, mitochondrial function, mRNA and protein contents. Adipocyte-specific Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, as well as adipocyte number and diameter, phenotypes that were associated with increased lipolysis, UCP-1 content (browning) and mRNA levels of pro-browning transcriptional factors C/EBPβ and ERRα. Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1α and PPARα in both visceral and subcutaneous fat. In brown adipocytes, however, Tsc1 deletion did not affect UCP-1 content and basal respiration. Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet. In conclusion, adipocyte-specific Tsc1 deletion enhances mitochondrial activity, induces browning and reduces visceral adiposity in mice. PMID:26923434

  20. [Significance of mTOR (mammalian target of rapamycin) activity in human lymphomas].

    PubMed

    Márk, Ágnes

    2014-06-01

    Neoplastic processes, tumor growth, and tumor cell proliferation and survival are often due to the altered activation of different signaling pathways. The increased activity of PI3K/AKT/mTOR signaling has been shown to be an important regulator of tumor growth in several solid tumors and in mantle cell lymphomas. The active form of mTOR kinase (mammalian target of rapamycin) is a key signaling molecule, and it exists in two different complexes, mTORC1 and mTORC2. In the present work, mTOR activity was investigated in different lymphoma types, in parallel with clinical data. We also examined in Hodgkin lymphomas (HL) the role of mTOR activity in survival mechanisms such as antiapoptotic protein expression and alterations in the microenvironment. We determined which lymphoma types display characteristic high mTOR activity in our TMA (tissue microarray) study. We observed that mTOR activity is increased in mitotic lymphoid cells compared to interphasic cells. The number of diffuse large B cell lymphoma (DLBCL) and HL cases was extended in a further set of TMA. We observed significantly higher mTOR activity in the non-centrum germinativum derived subtype of DLBCL than in the centrum germinativum derived subtype, which was a prognostic marker; 63% of mTOR active cases showed Rictor overexpression, indicating mTORC2 activity. High mTOR activity was also established in 92% of HL cases, which was linked to mTORC1. This finding was not a prognostic marker, however, it can be useful in targeted therapy. We observed the overexpression of the antiapoptotic protein BCL-xL and NFκB-p50 in the majority of mTOR active HLs. HLs showed high numbers of regulatory T cells in the microenvironment and high expression of galectin-1 in tumor cells and in the extracellular matrix, when compared to reactive lymph nodes. We confirmed that mTOR inhibition had significant antiproliferative and antiapoptotic effects in lymphoma cell lines and in lymphoma xenografts (HL, DLBCL, Burkitt lymphoma

  1. Reduced In-Plane, Low Frequency Helicopter Noise of an Active Flap Rotor

    NASA Technical Reports Server (NTRS)

    Sim, Ben W.; Janakiram, Ram D.; Barbely, Natasha L.; Solis, Eduardo

    2009-01-01

    Results from a recent joint DARPA/Boeing/NASA/Army wind tunnel test demonstrated the ability to reduce in-plane, low frequency noise of the full-scale Boeing-SMART rotor using active flaps. Test data reported in this paper illustrated that acoustic energy in the first six blade-passing harmonics could be reduced by up to 6 decibels at a moderate airspeed, level flight condition corresponding to advance ratio of 0.30. Reduced noise levels were attributed to selective active flap schedules that modified in-plane blade airloads on the advancing side of the rotor, in a manner, which generated counteracting acoustic pulses that partially offset the negative pressure peaks associated with in-plane, steady thickness noise. These favorable reduced-noise operating states are a strong function of the active flap actuation amplitude, frequency and phase. The associated noise reductions resulted in reduced aural detection distance by up to 18%, but incurred significant vibratory load penalties due to increased hub shear forces. Small reductions in rotor lift-to-drag ratios, of no more than 3%, were also measured

  2. Significance probability mapping: an aid in the topographic analysis of brain electrical activity.

    PubMed

    Duffy, F H; Bartels, P H; Burchfiel, J L

    1981-05-01

    We illustrate the application of significance probability mapping (SPM) to the analysis of topographic maps of spectral analyzed EEG and visual evoked potential (VEP) activity from patients with brain tumors, boys with dyslexia, and control subjects. When the VEP topographic plots of tumor patients were displayed as number of standard deviations from a reference mean, more subjects were correctly identified than by inspection of the underlying raw data. When topographic plots of EEG alpha activity obtained while listening to speech or music were compared by t statistic to plots of resting alpha activity, regions of cortex presumably activated by speech or music were delineated. DIfferent regions were defined in dyslexic boys and controls. We propose that SPM will prove valuable in the regional localization of normal and abnormal functions in other clinical situations. PMID:6165544

  3. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.

    PubMed

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A; Cardozo, Christopher P

    2011-10-14

    Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy. PMID:21945932

  4. The potential for Bayesian compressive sensing to significantly reduce electron dose in high-resolution STEM images.

    PubMed

    Stevens, Andrew; Yang, Hao; Carin, Lawrence; Arslan, Ilke; Browning, Nigel D

    2014-02-01

    The use of high-resolution imaging methods in scanning transmission electron microscopy (STEM) is limited in many cases by the sensitivity of the sample to the beam and the onset of electron beam damage (for example, in the study of organic systems, in tomography and during in situ experiments). To demonstrate that alternative strategies for image acquisition can help alleviate this beam damage issue, here we apply compressive sensing via Bayesian dictionary learning to high-resolution STEM images. These computational algorithms have been applied to a set of images with a reduced number of sampled pixels in the image. For a reduction in the number of pixels down to 5% of the original image, the algorithms can recover the original image from the reduced data set. We show that this approach is valid for both atomic-resolution images and nanometer-resolution studies, such as those that might be used in tomography datasets, by applying the method to images of strontium titanate and zeolites. As STEM images are acquired pixel by pixel while the beam is scanned over the surface of the sample, these postacquisition manipulations of the images can, in principle, be directly implemented as a low-dose acquisition method with no change in the electron optics or the alignment of the microscope itself. PMID:24151325

  5. Activation of protease-activated receptor 2 reduces glioblastoma cell apoptosis

    PubMed Central

    2014-01-01

    Background The pathogenesis of glioma is unclear. The disturbance of the apoptosis process plays a critical role in glioma growth. Factors regulating the apoptosis process are to be further understood. This study aims to investigate the role of protease activated receptor-2 (PAR2) in regulation the apoptosis process in glioma cells. Results The results showed that U87 cells and human glioma tissue expressed PAR2. Exposure to tryptase, or the PAR2 active peptide, increased STAT3 phosphorylation in the radiated U87 cells, reduced U87 cell apoptosis, suppressed the expression of p53 in U87 cells. Conclusions Activation of PAR2 can reduce the radiated U87 cell apoptosis via modulating the expression of p53. The results implicate that PAR2 may be a novel therapeutic target in the treatment of glioma. PMID:24670244

  6. Are secular correlations between sunspots, geomagnetic activity, and global temperature significant?

    USGS Publications Warehouse

    Love, J.J.; Mursula, K.; Tsai, V.C.; Perkins, D.M.

    2011-01-01

    Recent studies have led to speculation that solar-terrestrial interaction, measured by sunspot number and geomagnetic activity, has played an important role in global temperature change over the past century or so. We treat this possibility as an hypothesis for testing. We examine the statistical significance of cross-correlations between sunspot number, geomagnetic activity, and global surface temperature for the years 1868-2008, solar cycles 11-23. The data contain substantial autocorrelation and nonstationarity, properties that are incompatible with standard measures of cross-correlational significance, but which can be largely removed by averaging over solar cycles and first-difference detrending. Treated data show an expected statistically- significant correlation between sunspot number and geomagnetic activity, Pearson p < 10-4, but correlations between global temperature and sunspot number (geomagnetic activity) are not significant, p = 0.9954, (p = 0.8171). In other words, straightforward analysis does not support widely-cited suggestions that these data record a prominent role for solar-terrestrial interaction in global climate change. With respect to the sunspot-number, geomagnetic-activity, and global-temperature data, three alternative hypotheses remain difficult to reject: (1) the role of solar-terrestrial interaction in recent climate change is contained wholly in long-term trends and not in any shorter-term secular variation, or, (2) an anthropogenic signal is hiding correlation between solar-terrestrial variables and global temperature, or, (3) the null hypothesis, recent climate change has not been influenced by solar-terrestrial interaction. ?? 2011 by the American Geophysical Union.

  7. Crossing the telemedicine chasm: have the U.S. barriers to widespread adoption of telemedicine been significantly reduced?

    PubMed

    LeRouge, Cynthia; Garfield, Monica J

    2013-12-01

    Barriers have challenged widespread telemedicine adoption by health care organizations for 40 years. These barriers have been technological, financial, and legal and have also involved business strategy and human resources. The article canvasses recent trends-events and activities in each of these areas as well as US health reform activities that might help to break down these barriers. The key to telemedicine success in the future is to view it as an integral part of health care services and not as a stand-alone project. Telemedicine must move from experimental and separate to integrated and equivalent to other health services within health care organizations. Furthermore, telemedicine serves as vital connective tissue for expanding health care organization networks. PMID:24287864

  8. Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice.

    PubMed

    Shaw, Maureen A; Kombrinck, Keith W; McElhinney, Kathryn E; Sweet, David R; Flick, Matthew J; Palumbo, Joseph S; Cheng, Mei; Esmon, Naomi L; Esmon, Charles T; Brill, Alexander; Wagner, Denisa D; Degen, Jay L; Mullins, Eric S

    2016-08-01

    Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to α-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIa(MZ)). FIIa(MZ) has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIa(MZ), mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIa(MZ) Homozygous fII(MZ) mice are viable, express fII levels comparable with fII(WT) mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIa(MZ) enzyme activity, platelet aggregation by fII(MZ) is similar to fII(WT) Consistent with prior analyses of human fIIa(MZ), significant prolongation of clotting times was observed for fII(MZ) plasma. Adult fII(MZ) animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fII(MZ) mice had 2 significant phenotypic advantages over fII(WT) animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIa(MZ) in vivo. PMID:27252233

  9. Pinelliae rhizoma, a toxic chinese herb, can significantly inhibit CYP3A activity in rats.

    PubMed

    Wu, Jinjun; Cheng, Zaixing; He, Shugui; Shi, Jian; Liu, Shuqiang; Zhang, Guiyu; Zhu, Lijun; Liu, Liang; Liu, Zhongqiu; Lin, Na; Lu, Linlin

    2015-01-01

    Raw Pinelliae Rhizoma (RPR) is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP) and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA), are more commonly applied and administered concomitantly with other chemical drugs, such as cough medications. This study aimed to investigate the effects of RPR, PRP, and PRPZA on CYP3A activity. Testosterone (Tes) and buspirone (BP) were used as specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was determined by the metabolite formation ratios from the substrates. Ex vivo results show that the metabolite formation ratios from Tes significantly decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in rats. CYP3A protein and mRNA levels were determined to explore the underlying mechanism. These levels showed marked and consistent down-regulation with CYP3A activity. A significant decrease in metabolite formation ratios from BP was also found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity. Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may cause drug-drug interactions. Clinical use of PR-related formulae should be monitored carefully to avoid adverse interactions. PMID:25574821

  10. [Plasminogen activator system and its clinical significance in patients with a malignant disease].

    PubMed

    Halámková, J; Kiss, I; Tomásek, J; Pavlovský, Z; Cech, Z; Tutek, S; Hanáková, L; Moulis, M; Penka, M

    2011-01-01

    Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, a serine protease participating in the activation of matrixmetaloproteinases, latent elastases, growth factors and cytokines involved in the degradation of extracellular matrix elements. Together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI-1, PAI-2, PAI-3 and protease nexin), it forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. Plasminogen activator inhibitor 1 inhibits uPA-dependent invasiveness of some cancer cell lines. The vitronectin-PAI-1 complex inhibits migration of smooth muscle cells by binding alpha(v)beta3 integrin to vitronectin. PAI-1 or its deficiency interferes with signalling pathways such as PI3K/Akt and JAK/STAT and it is included in the processes of maintaining the integrity of the endothelial cells and thereby regulation of cell death. PAI-1 affects apoptosis by reducing cell adhesion and functioning of intracellular signalling pathways. The individual components of PAS undoubtedly play an important role in angiogenesis and metastasising of malignant tumours. In the near future, results of published studies with various types of cancer could be reflected in diagnostic and therapeutic algorithms and, at the same time, could serve as the goal for targeted therapies. PMID:22257230

  11. Implementation and Operational Research: Expedited Results Delivery Systems Using GPRS Technology Significantly Reduce Early Infant Diagnosis Test Turnaround Times.

    PubMed

    Deo, Sarang; Crea, Lindy; Quevedo, Jorge; Lehe, Jonathan; Vojnov, Lara; Peter, Trevor; Jani, Ilesh

    2015-09-01

    The objective of this study was to quantify the impact of a new technology to communicate the results of an infant HIV diagnostic test on test turnaround time and to quantify the association between late delivery of test results and patient loss to follow-up. We used data collected during a pilot implementation of Global Package Radio Service (GPRS) printers for communicating results in the early infant diagnosis program in Mozambique from 2008 through 2010. Our dataset comprised 1757 patient records, of which 767 were from before implementation and 990 from after implementation of expedited results delivery system. We used multivariate logistic regression model to determine the association between late result delivery (more than 30 days between sample collection and result delivery to the health facility) and the probability of result collection by the infant's caregiver. We used a sample selection model to determine the association between late result delivery to the facility and further delay in collection of results by the caregiver. The mean test turnaround time reduced from 68.13 to 41.05 days post-expedited results delivery system. Caregivers collected only 665 (37.8%) of the 1757 results. After controlling for confounders, the late delivery of results was associated with a reduction of approximately 18% (0.44 vs. 0.36; P < 0.01) in the probability of results collected by the caregivers (odds ratio = 0.67, P < 0.05). Late delivery of results was also associated with a further average increase in 20.91 days of delay in collection of results (P < 0.01). Early infant diagnosis program managers should further evaluate the cost-effectiveness of operational interventions (eg, GPRS printers) that reduce delays. PMID:26068719

  12. Significant others and contingencies of self-worth: activation and consequences of relationship-specific contingencies of self-worth.

    PubMed

    Horberg, E J; Chen, Serena

    2010-01-01

    Three studies tested the activation and consequences of contingencies of self-worth associated with specific significant others, that is, relationship-specific contingencies of self-worth. The results showed that activating the mental representation of a significant other with whom one strongly desires closeness led participants to stake their self-esteem in domains in which the significant other wanted them to excel. This was shown in terms of self-reported contingencies of self-worth (Study 1), in terms of self-worth after receiving feedback on a successful or unsatisfactory performance in a relationship-specific contingency domain (Study 2), and in terms of feelings of reduced self-worth after thinking about a failure in a relationship-specific contingency domain (Study 3). Across studies, a variety of contingency domains were examined. Furthermore, Study 3 showed that failing in an activated relationship-specific contingency domain had negative implications for current feelings of closeness and acceptance in the significant-other relationship. Overall, the findings suggest that people's contingencies of self-worth depend on the social situation and that performance in relationship-specific contingency domains can influence people's perceptions of their relationships. PMID:20053033

  13. Reduced serum inhibition of platelet-activating factor activity in preeclampsia.

    PubMed

    Benedetto, C; Massobrio, M; Bertini, E; Abbondanza, M; Enrieu, N; Tetta, C

    1989-01-01

    We determined in normal nonpregnant (group 1) women, normal pregnant (group 2) women, and patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity, the presence of detectable amounts of platelet-activating factor in the blood, and platelet responsiveness in vitro to platelet-activating factor, and to other agonists (adenosine diphosphate, collagen, and ristocetin), and prostacyclin (prostaglandin I2). In patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity was significantly lower than that in groups 1 and 2. However, no detectable amounts of platelet-activating factor were observed. The mean values of platelet aggregation induced by platelet-activating factor, adenosine diphosphate, collagen and ristocetin, and the prostaglandin I2-inhibitory concentration of 50% which is inversely correlated with platelet sensitivity to prostaglandin I2, were not significantly different between groups 2 and 3. It is suggested that in preeclampsia the defect in serum inhibitory potential of platelet-activating factor--induced platelet aggregation may contribute to the disturbance in the homeostatic balance between proaggregant and antiaggregant substances. PMID:2912073

  14. Shortened cecropin A-melittin hybrids. Significant size reduction retains potent antibiotic activity.

    PubMed

    Andreu, D; Ubach, J; Boman, A; Wåhlin, B; Wade, D; Merrifield, R B; Boman, H G

    1992-01-20

    We have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin A (CA) and melittin (M). We now report a substantial reduction in size at the C-terminal section of the highly active hybrid CA(1-8)M(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule. In particular, the 15-residue hybrids CA(1-7)M(2-9), CA(1-7)M(4-11) and CA(1-7)M(5-12) are the shortest cecropin-based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size. Their reduced size and highly alpha-helical structure require an alternative mechanism for their interaction with bacterial membranes. PMID:1733777

  15. Effect of Lead stress on phosphatase activity and reducing power assay of Triticum aestivum.

    PubMed

    Gubrelay, U; Agnihotri, R K; Shrotriya, S; Sharma, R

    2015-01-01

    Lead (Pb) is a highly toxic heavy metal for both plants and animals; the environment is increasingly polluted with heavy metals and reduces crop productivity. Plants possess homeostatic mechanisms that allow them to keep correct concentrations of essential metal ions in cellular compartments and to minimize the damaging effects of an excess of nonessential ones. One of their adverse effects on plants are the generation of harmful active oxygen species, leading to oxidative stress and the antioxidative activity seems to be of fundamental importance for adaptive response of plant against environmental stress. The present study explores the effects of lead (soil treated twice/ week) with (10, 30 and 60 mM) on the specific activities of phosphatases which might lead to reducing power assay in (Triticum aestivum PBW344) seedling. A significant decrease in the redox potential of shoot compared to root was observed at the similar concentration of lead. A similar trend on leaves was also noted. Acid and alkaline phosphatase activities were significantly higher in roots than in shoot at all the three concentration of lead i.e. 10, 30 and 60 mM, compared to controls. The above mentioned changes were more pronounced at 60 mM concentration of lead than two other concentrations. These results lead us to suggest that increased lead concentration in soil might lead to adverse effects on plant growth and phosphatase activities. PMID:26107501

  16. [Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)].

    PubMed

    Nishimoto, A; Miura, N; Oshimura, M

    1998-05-01

    To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease. PMID:9613131

  17. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    PubMed

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense. PMID:26643168

  18. Activity in ventromedial prefrontal cortex during self-related processing: positive subjective value or personal significance?

    PubMed

    Kim, Kyungmi; Johnson, Marcia K

    2015-04-01

    Well-being and subjective experience of a coherent world depend on our sense of 'self' and relations between the self and the environment (e.g. people, objects and ideas). The ventromedial prefrontal cortex (vMPFC) is involved in self-related processing, and disrupted vMPFC activity is associated with disruptions of emotional/social functioning (e.g. depression and autism). Clarifying precise function(s) of vMPFC in self-related processing is an area of active investigation. In this study, we sought to more specifically characterize the function of vMPFC in self-related processing, focusing on two alternative accounts: (i) assignment of positive subjective value to self-related information and (ii) assignment of personal significance to self-related information. During functional magnetic resonance imaging (fMRI), participants imagined owning objects associated with either their perceived ingroup or outgroup. We found that for ingroup-associated objects, vMPFC showed greater activity for objects with increased than decreased post-ownership preference. In contrast, for outgroup-associated objects, vMPFC showed greater activity for objects with decreased than increased post-ownership preference. Our findings support the idea that the function of vMPFC in self-related processing may not be to represent/evaluate the 'positivity' or absolute preference of self-related information but to assign personal significance to it based on its meaning/function for the self. PMID:24837477

  19. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    PubMed

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  20. Precision feeding can significantly reduce lysine intake and nitrogen excretion without compromising the performance of growing pigs.

    PubMed

    Andretta, I; Pomar, C; Rivest, J; Pomar, J; Radünz, J

    2016-07-01

    This study was developed to assess the impact on performance, nutrient balance, serum parameters and feeding costs resulting from the switching of conventional to precision-feeding programs for growing-finishing pigs. A total of 70 pigs (30.4±2.2 kg BW) were used in a performance trial (84 days). The five treatments used in this experiment were a three-phase group-feeding program (control) obtained with fixed blending proportions of feeds A (high nutrient density) and B (low nutrient density); against four individual daily-phase feeding programs in which the blending proportions of feeds A and B were updated daily to meet 110%, 100%, 90% or 80% of the lysine requirements estimated using a mathematical model. Feed intake was recorded automatically by a computerized device in the feeders, and the pigs were weighed weekly during the project. Body composition traits were estimated by scanning with an ultrasound device and densitometer every 28 days. Nitrogen and phosphorus excretions were calculated by the difference between retention (obtained from densitometer measurements) and intake. Feeding costs were assessed using 2013 ingredient cost data. Feed intake, feed efficiency, back fat thickness, body fat mass and serum contents of total protein and phosphorus were similar among treatments. Feeding pigs in a daily-basis program providing 110%, 100% or 90% of the estimated individual lysine requirements also did not influence BW, body protein mass, weight gain and nitrogen retention in comparison with the animals in the group-feeding program. However, feeding pigs individually with diets tailored to match 100% of nutrient requirements made it possible to reduce (P<0.05) digestible lysine intake by 26%, estimated nitrogen excretion by 30% and feeding costs by US$7.60/pig (-10%) relative to group feeding. Precision feeding is an effective approach to make pig production more sustainable without compromising growth performance. PMID:26759074

  1. Voluntary access to a warm plate reduces hyperactivity in activity-based anorexia.

    PubMed

    Hillebrand, Jacquelien J G; de Rijke, Corine E; Brakkee, Jan H; Kas, Martien J H; Adan, Roger A H

    2005-06-01

    Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa. In ABA, scheduled feeding in combination with voluntary wheel running leads to hyperactivity, reduced food intake, severe body weight loss and hypothermia. In this study it was investigated whether hyperactivity in ABA could be reduced by introducing a warm plate (which was voluntary accessible and did not influence ambient temperature) into a part of the cage. In ad libitum fed rats, the presence of the warm plate did not influence body temperature, running wheel activity (RWA), body weight or food intake. During ABA, however, rats preferred the warm plate and hypothermia was prevented, while hyperactivity and body weight loss were significantly reduced when compared to ABA rats without a plate. Correlation analysis revealed a significant association between basal body temperature and RWA during the light phase in ABA rats. However, there was no evidence that initiation of light phase RWA was a result of hypothermia. These data suggest that ABA rats prefer to prevent hypothermia passively by choosing a warm plate rather than actively regulating body temperature by hyperactivity. PMID:15924912

  2. Piano Playing Reduces Stress More than Other Creative Art Activities

    ERIC Educational Resources Information Center

    Toyoshima, Kumiko; Fukui, Hajime; Kuda, Kiyoto

    2011-01-01

    Few studies have been conducted on the physiological effects of creative art activities. In this study, the effects of creative art activities on human stress were investigated, and their effects were compared in 57 healthy college students (27 males and 30 females). Subjects were divided into four groups, each of which participated in 30-minute…

  3. Baroreflex Activation Therapy in Heart Failure With Reduced Ejection Fraction: Available Data and Future Perspective.

    PubMed

    Halbach, Marcel; Fritz, Thorsten; Madershahian, Navid; Pfister, Roman; Reuter, Hannes

    2016-04-01

    Progression of heart failure with reduced ejection fraction (HFrEF) is promoted by sympathovagal imbalance. Baroreflex activation therapy, i.e., electrical stimulation of baroreceptors at the carotid sinus, can restore sympathovagal balance. Large animal studies of baroreflex activation therapy revealed improvements in cardiac function, susceptibility to ventricular arrhythmias, and a survival benefit as compared to untreated controls. Recently, the first randomized and controlled trial of optimal medical and device therapy alone or plus baroreflex activation therapy in patients suffering from HFrEF was published. It demonstrated a reasonable safety profile in this severely ill patient population. Moreover, the study found significant improvements in New York Heart Association class, quality of life, 6-min walk distance, and NT-proBNP levels. This review provides an overview on baroreflex activation therapy for the treatment of HFrEF-from the concept and preclinical findings to most recent clinical data and upcoming trials. PMID:26879389

  4. Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System

    PubMed Central

    Ciccocioppo, Roberto; Economidou, Daina; Rimondini, Roberto; Sommer, Wolfgang; Massi, Maurizio; Heilig, Markus

    2011-01-01

    Background Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at μ-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. Methods Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Results Similar to prototypical μ-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 μg/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine. Conclusions Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism. PMID:16533497

  5. α-Mangostin Reduced ER Stress-mediated Tumor Growth through Autophagy Activation

    PubMed Central

    Kim, Sung-Jin; Hong, Eun-Hye; Lee, Bo-Ra; Park, Moon-Ho; Kim, Ji-Won; Pyun, A-Rim; Kim, Yeon-Jeong; Chang, Sun-Young; Chin, Young-Won

    2012-01-01

    α-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of α-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although α-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum Ca2+ ATPase like thapsigargin, it showed different activity for autophagy regulation. In the current study, we found that α-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of α-Mangostin daily for three days. However, the activation of autophagy by α-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of eIF2α, thapsigargin-induced ER stress was significantly reduced by α-Mangostin. However, coadministration of thapsigargin with α-Mangostin completely blocked the antitumor activity of α-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of α-Mangostin can be ascribable to the autophagy activation rather than ER stress induction. PMID:23396851

  6. Significant Enhancement of Water Splitting Activity of N-Carbon Electrocatalyst by Trace Level Co Doping.

    PubMed

    Bayatsarmadi, Bita; Zheng, Yao; Tang, Youhong; Jaroniec, Mietek; Qiao, Shi-Zhang

    2016-07-01

    Replacement of precious metal electrocatalysts with highly active and cost efficient alternatives for complete water splitting at low voltage has attracted a growing attention in recent years. Here, this study reports a carbon-based composite co-doped with nitrogen and trace amount of metallic cobalt (1 at%) as a bifunctional electrocatalyst for water splitting at low overpotential and high current density. An excellent electrochemical activity of the newly developed electrocatalyst originates from its graphitic nanostructure and highly active Co-Nx sites. In the case of carefully optimized sample of this electrocatalyst, 10 mA cm(-2) current density can be achieved for two half reactions in alkaline solutions-hydrogen evolution reaction and oxygen evolution reaction-at low overpotentials of 220 and 350 mV, respectively, which are smaller than those previously reported for nonprecious metal and metal-free counterparts. Based on the spectroscopic and electrochemical investigations, the newly identified Co-Nx sites in the carbon framework are responsible for high electrocatalytic activity of the Co,N-doped carbon. This study indicates that a trace level of the introduced Co into N-doped carbon can significantly enhance its electrocatalytic activity toward water splitting. PMID:27246288

  7. Increased expression of β-glucosidase A in Clostridium thermocellum 27405 significantly increases cellulase activity

    PubMed Central

    Maki, Miranda L.; Armstrong, Lachlan; Leung, Kam Tin; Qin, Wensheng

    2013-01-01

    β-glucosidase A (bglA) in Clostridium thermocellum 27405 was increased by expression from shuttle vector pIBglA in attempts to increase cellulase activity and ethanol titer by lowering the end product inhibition of cellulase. Through a modified electrotransformation protocol C. thermocellum transformant (+MCbglA) harbouring pIBglA was produced. The β-glucosidase activity of +MCbglA was 2.3- and 1.6-fold greater than wild-type (WT) during late log and stationary phases of growth. Similarly, total cellulase activity of +MCbglA was shown to be 1.7-, 2.3- and 1.6-fold greater than WT during, log, late log and stationary phases of growth. However, there was no significant correlation found between increased cellulase activity and increased ethanol titers for +MCbglA compared with the WT. C. thermocellum has industrial potential for consolidated bioprocessing (CBP) to make a more cost effective production of biofuels; however, the hydrolysis rate of the strain is still hindered by end product inhibition. We successfully increased total cellulase activity by increased expression of bglA and thereby increased the productivity of C. thermocellum during the hydrolysis stage in CBP. Our work also lends insights into the complex metabolism of C. thermocellum for future improvement of this strain. PMID:22922214

  8. Shipwreck rates and tree rings suggest reduced North Atlantic tropical cyclone activity during the Maunder Minimum.

    NASA Astrophysics Data System (ADS)

    Harley, G. L.; Trouet, V.; Dominguez Delmas, M.

    2014-12-01

    The observational record of North Atlantic TCs is too short to inform our understanding of decadal-scale climatic controls on TC regimes. We combined two new annual-resolution proxies of Atlantic storm activity to extend the observational TC record back to the 16th Century. A tree-growth suppression chronology (1707-2010 CE) from the Florida Keys, U.S.A. captures 91% of observed North Atlantic TCs (1850-2010 CE) and shares significant peak events with a documentary time series of Spanish shipwrecks in the Caribbean (1495-1820). Decadal-scale shipwreck rates were lowest during the Maunder Minimum (ca. 1645-1715), indicating that cooler Atlantic sea surface temperatures (SSTs) during this period reduced Caribbean TC activity. Our results support global-scale climate proxy data and suggest that cooler tropical Atlantic SSTs and a generally negative mode of the North Atlantic Oscillation during the Little Ice Age reduced TC frequency.

  9. Reduced Denitration Activity in Peripheral Lung of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Osoata, Grace O.; Ito, Misako; Elliot, Mark; Hogg, James; Barnes, Peter J.

    2012-01-01

    Background Accumulation of nitrated protein is seen in peripheral lung and cells from patients with chronic obstructive pulmonary disease (COPD). Nitrated protein causes abnormal protein function, but the nitration was believed to be an irreversible process. However, there are accumulating evidences that this process is reversible by an active denitration pathway. The aim of this study is to detect denitration activity in protein extracts from peripheral lung tissue of COPD and to compare with those in healthy subjects. Materials and Methods Peripheral lung tissue from 4 healthy, 4 smokers without COPD, 4 GOLD stage 1 and 4 GOLD stage 2 were used for denitration assay. Denitration activity was determined as reduction of nitro-tyrosine level of nitrated histone protein after incubation with protein extracts from peripheral lung, which was determined by western blotting. In addition, RNA is extracted from peripheral lung of 8 healthy, 7 smoking control, 8 stage 1 and 2 COPD and 10 stage 3 and 4 COPD and nitrate reductase mRNA expression was determined by real time RT-PCR. Results Peripheral lung protein extracts from healthy subjects reduced nitro-tyrosine level of nitrated histone. Thus, we were able to show denitration activity in peripheral lungs. The denitration activity was slightly reduced in smoking controls, and significantly reduced in COPD patients. We also showed that the expression of the human homologue of nitrate reductase (chytochrome β2 reductase), a potential candidate of denitrase, was significanty reduced in COPD lung. Conclusion This study suggests that accumulation of nitrated protein in lung tissue of COPD may, at least in part, be induced by a reduction in denitration activity or nitrate reductase. PMID:25191434

  10. Antisecretory and antimotility activity of Aconitum heterophyllum and its significance in treatment of diarrhea

    PubMed Central

    Prasad, Satyendra K.; Jain, Divya; Patel, Dinesh K.; Sahu, Alakh N.; Hemalatha, Siva

    2014-01-01

    Aim: The roots of the plant Aconitum heterophyllum (EAH) are traditionally used for curing hysteria, throat infection, dyspepsia, abdominal pain, diabetes, and diarrhea. Therefore, the present study was undertaken to determine the mechanism involved in the anti-diarrheal activity of roots of A. heterophyllum. Materials and Methods: Ant-diarrheal activity of ethanol extract at 50, 100, and 200 mg/kg p.o. was evaluated using fecal excretion and castor oil-induced diarrhea models, while optimized dose, that is, 100 mg/kg p.o. was further subjected to small intestinal transit, intestinal fluids accumulation, PGE2-induced enteropooling and gastric emptying test. To elucidate the probable mechanism, various biochemical parameters and Na+, K+ concentration in intestinal fluids were also determined. Further, antibacterial activity of extract along with its standardization using aconitine as a marker with the help of HPLC was carried out. Results: The results depicted a significant (P < 0.05) reduction in normal fecal output at 100 and 200 mg/kg p.o. of extract after 5th and 7th h of treatment. Castor oil-induced diarrhea model demonstrated a ceiling effect at 100 mg/kg p.o. with a protection of 60.185% from diarrhea. EAH at 100 mg/kg p.o. also showed significant activity in small intestinal transit, fluid accumulation, and PGE2-induced enteropooling models, which also restored the altered biochemical parameters and prevented Na+ and K+ loss. The extract with 0.0833% w/w of aconitine depicted a potential antibacterial activity of extract against microbes implicated in diarrhea. Conclusion: The study concluded antisecretory and antimotility effect of A. heterophyllum, which mediates through nitric oxide path way. PMID:24550590

  11. Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice.

    PubMed

    Maroso, Mattia; Balosso, Silvia; Ravizza, Teresa; Iori, Valentina; Wright, Christopher Ian; French, Jacqueline; Vezzani, Annamaria

    2011-04-01

    Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765. Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥ 50 mg/kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs. PMID:21431948

  12. Active Hemovigilance Significantly Improves Reporting of Acute Non-infectious Adverse Reactions to Blood Transfusion.

    PubMed

    Agnihotri, Naveen; Agnihotri, Ajju

    2016-09-01

    One of the key purposes of a hemovigilance program is to improve reporting of transfusion related adverse events and subsequent data-driven improvement in blood transfusion (BT) practices. We conducted a study over 3 years to assess the impact of healthcare worker training and an active feedback programme on reporting of adverse reactions to BTs. All hospitalized patients who required a BT were included in the study. Healthcare workers involved in BT to patients were sensitized and trained in adverse reaction reporting by conducting training sessions and meetings. All the transfused patients were 'actively' monitored for any acute adverse reaction by using a uniquely coded blood issue form. A total of 18,914 blood components transfused to 5785 different patients resulted in 61 adverse reaction episodes. This incidence of 0.32 % in our study was found to be significantly higher (p < 0.005) than that reported from the same region in the past. Red blood cell units were the most frequently transfused component and thus most commonly involved in an adverse reaction (42.6 %), however apheresis platelets had the highest chance of reaction per unit transfused (0.66 %). There was no mortality associated with the BT during the study period. An active surveillance program significantly improves reporting and management of adverse reactions to BTs. PMID:27429527

  13. The temporal structures and functional significance of scale-free brain activity

    PubMed Central

    He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

    2010-01-01

    SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  14. The temporal structures and functional significance of scale-free brain activity.

    PubMed

    He, Biyu J; Zempel, John M; Snyder, Abraham Z; Raichle, Marcus E

    2010-05-13

    Scale-free dynamics, with a power spectrum following P proportional to f(-beta), are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with beta being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  15. Preferential PPAR-α activation reduces neuroinflammation, and blocks neurodegeneration in vivo.

    PubMed

    Esmaeili, Mohammad A; Yadav, Shilpi; Gupta, Ravi Kr; Waggoner, Garrett R; Deloach, Abigail; Calingasan, Noel Y; Beal, M Flint; Kiaei, Mahmoud

    2016-01-15

    Neuroinflammation, immune reactivity and mitochondrial abnormalities are considered as causes and/or contributors to neuronal degeneration. Peroxisome proliferator-activated receptors (PPARs) regulate both inflammatory and multiple other pathways that are implicated in neurodegeneration. In the present study, we investigated the efficacy of fenofibrate (Tricor), a pan-PPAR agonist that activates PPAR-α as well as other PPARs. We administered fenofibrate to superoxide dismutase 1 (SOD1(G93A)) mice daily prior to any detectable phenotypes and then animal behavior, pathology and longevity were assessed. Treated animals showed a significant slowing of the progression of disease with weight loss attenuation, enhanced motor performance, delayed onset and survival extension. Histopathological analysis of the spinal cords showed that neuronal loss was significantly attenuated in fenofibrate-treated mice. Mitochondria were preserved as indicated by Cytochrome c immunostaining in the spinal cord, which maybe partly due to increased expression of the PPAR-γ co-activator 1-α. The total mRNA analysis revealed that neuroprotective and anti-inflammatory genes were elevated, while neuroinflammatory genes were down-regulated. This study demonstrates that the activation of PPAR-α action via fenofibrate leads to neuroprotection by both reducing neuroinflammation and protecting mitochondria, which leads to a significant increase in survival in SOD1(G93A) mice. Therefore, the development of therapeutic strategies to activate PPAR-α as well as other PPARs may lead to new therapeutic agents to slow or halt the progression of amyotrophic lateral sclerosis. PMID:26604138

  16. Ischemic preconditioning reduces hemodynamic response during metaboreflex activation.

    PubMed

    Mulliri, Gabriele; Sainas, Gianmarco; Magnani, Sara; Palazzolo, Girolamo; Milia, Nicola; Orrù, Andrea; Roberto, Silvana; Marongiu, Elisabetta; Milia, Raffaele; Crisafulli, Antonio

    2016-05-01

    Ischemic preconditioning (IP) has been shown to improve exercise performance and to delay fatigue. However, the precise mechanisms through which IP operates remain elusive. It has been hypothesized that IP lowers the sensation of fatigue by reducing the discharge of group III and IV nerve endings, which also regulate hemodynamics during the metaboreflex. We hypothesized that IP reduces the blood pressure response during the metaboreflex. Fourteen healthy males (age between 25 and 48 yr) participated in this study. They underwent the following randomly assigned protocol: postexercise muscle ischemia (PEMI) test, during which the metaboreflex was elicited after dynamic handgrip; control exercise recovery session (CER) test; and PEMI after IP (IP-PEMI) test. IP was obtained by occluding forearm circulation for three cycles of 5 min spaced by 5 min of reperfusion. Hemodynamics were evaluated by echocardiography and impedance cardiography. The main results were that after IP the mean arterial pressure response was reduced compared with the PEMI test (means ± SD +3.37 ± 6.41 vs. +9.16 ± 7.09 mmHg, respectively). This was the consequence of an impaired venous return that impaired the stroke volume during the IP-PEMI more than during the PEMI test (-1.43 ± 15.35 vs. +10.28 ± 10.479 ml, respectively). It was concluded that during the metaboreflex, IP affects hemodynamics mainly because it impairs the capacity to augment venous return and to recruit the cardiac preload reserve. It was hypothesized that this is the consequence of an increased nitric oxide production, which reduces the possibility to constrict venous capacity vessels. PMID:26936782

  17. The crowded sea: incorporating multiple marine activities in conservation plans can significantly alter spatial priorities.

    PubMed

    Mazor, Tessa; Possingham, Hugh P; Edelist, Dori; Brokovich, Eran; Kark, Salit

    2014-01-01

    Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic

  18. The Crowded Sea: Incorporating Multiple Marine Activities in Conservation Plans Can Significantly Alter Spatial Priorities

    PubMed Central

    Mazor, Tessa; Possingham, Hugh P.; Edelist, Dori; Brokovich, Eran; Kark, Salit

    2014-01-01

    Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic

  19. Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

    PubMed Central

    de Vente, Wieke; van Amsterdam, Jan G. C.; Olff, Miranda; Kamphuis, Jan H.; Emmelkamp, Paul M. G.

    2015-01-01

    There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD). Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA) axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females) with burnout on sickness absence and 40 healthy participants (16 males and 24 females) were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase) were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis. PMID:26557670

  20. Significant correlation between refractive index and activity of mitochondria: single mitochondrion study

    PubMed Central

    Haseda, Keisuke; Kanematsu, Keita; Noguchi, Keiichi; Saito, Hiromu; Umeda, Norihiro; Ohta, Yoshihiro

    2015-01-01

    Measurements of refractive indices (RIs) of intracellular components can provide useful information on the structure and function of cells. The present study reports, for the first time, determination of the RI of an isolated mitochondrion in isotonic solution using retardation-modulated differential interference contrast microscopy. The value was 1.41 ± 0.01, indicating that mitochondria are densely packed with molecules having high RIs. Further, the RIs of each mitochondrion were significantly correlated with the mitochondrial membrane potential, an index of mitochondrial activity. These results will provide useful information on the structures and functions of cells based on the intracellular distribution of RIs. PMID:25798310

  1. Potential association of reduced cholinesterase activity with Trypanosoma evansi pathogenesis in buffaloes.

    PubMed

    Singh, Shanker K; Singh, Vivek K; Yadav, Brajesh K; Nakade, Udayraj P; Kumari, Priyambada; Srivastava, Mukesh K; Sharma, Abhishek; Choudhary, Soumen; Swain, Dilip; Garg, Satish K

    2016-07-30

    The present study aimed to investigate the association of cholinesterase activity with trypanosomosis in buffaloes. Thirty-three clinical cases of trypanosomosis in water buffaloes, found positive for trypomastigotes of T. evansi on blood smear examination, were divided into two groups based on clinical manifestations. Twenty diseased buffaloes revealing only common clinical signs were allocated to Group I, while the remaining 13 buffaloes showing common clinical manifestations along with neurological disturbances were allocated to Group II. Twelve clinically healthy buffaloes, free from any haemoprotozoa infection, were kept as healthy control (Group III). Blood samples were collected from buffaloes of all three groups to determine serum cholinesterase activity. Compared to buffaloes of healthy control group, cholinesterase activity in T. evansi-infected buffaloes of Group I and II was significantly (P<0.001) lower. However, no significant difference was observed in cholinesterase activity between the T. evansi-infected buffaloes exhibiting neurological disorders and no neurological disorders. Summing up, reduced cholinesterase activity seems to be associated with the pathogenesis of natural T. evansi infection and its clinical manifestations in buffaloes possibly by evading immune response. Further studies are warranted on association of cholinesterase activity in T. evansi-infected buffaloes with neurological disorders. PMID:27369572

  2. Reduced Frontal Activation with Increasing 2nd Language Proficiency

    ERIC Educational Resources Information Center

    Stein, Maria; Federspiel, Andrea; Koenig, Thomas; Wirth, Miranka; Lehmann, Christoph; Wiest, Roland; Strik, Werner; Brandeis, Daniel; Dierks, Thomas

    2009-01-01

    The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second…

  3. Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis

    PubMed Central

    Xu, Dong-Ling; Liu, Xiao-Bo; Bi, Shao-jie; Zhao, Tong; Sui, Shu-Jian; Ji, Xiao-Ping

    2016-01-01

    Purpose Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. Materials and Methods Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg·kg-1·d-1) and high-dose darapladib (50 mg·kg-1·d-1) interventions were then administered over the course of 2 weeks. Results The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05). Conclusion Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis. PMID:26847282

  4. Systems of meaning and transference: Implicit significant-other activation evokes shared reality.

    PubMed

    Przybylinski, Elizabeth; Andersen, Susan M

    2015-10-01

    Evidence shows that representations of significant others (SOs) are used in interpersonal relations-for example, in the social-cognitive process of transference (see Andersen & Chen, 2002), a process that is assumed to serve meaning-making functions (Glassman & Andersen, 1999b). Five studies tested the more specific notion that implicit activation of an SO representation in transference should indirectly activate the worldview shared with the SO, leading to its active pursuit, validation, and protection. Shared worldviews were assessed beforehand, both idiographically, as values (Studies 1 and 4), and nomothetically, as political ideology or religious beliefs (Studies 2, 3, and 5). In each experiment, participants learned about new persons, one subtly resembling their own SO. Transference was assessed (memory bias; positive evaluation; see Andersen, Reznik, & Manzella, 1996) and, crucially, as predicted, when considering the new person resembling their SO (vs. the control persons), participants showed faster response latencies in a lexical decision task to words reflecting the worldview shared with the SO (vs. held only personally, Studies 1-3, or only by the SO, Study 3). With this person, they also anticipated a more meaningful interaction and actively socially tuned to the SO-shared worldview, selecting conversation topics reflecting the SO-shared worldview (vs. personally held or SO-held topics, Studies 1-3). Finally, threatening the SO-shared worldview with this person (vs. threatening personally held, SO-held, or irrelevant worldviews) prompted goal activation to restore the disrupted meaning (Studies 4 and 5), assessed by response latency in a lexical decision task. Transference thus evokes shared meaning systems and serves epistemic functions. PMID:26414844

  5. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota

    PubMed Central

    Mai, Volker; Ukhanova, Maria; Reinhard, Mary K; Li, Manrong; Sulakvelidze, Alexander

    2015-01-01

    We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota. PMID:26909243

  6. Pertussis toxin analog with reduced enzymatic and biological activities is a protective immunogen.

    PubMed Central

    Kimura, A; Mountzouros, K T; Schad, P A; Cieplak, W; Cowell, J L

    1990-01-01

    Bordetella pertussis TOX3201 has a 12-base-pair insertion in the S1 subunit gene of pertussis toxin (PTX), which encodes for a 4-amino-acid insertion between residues 107 and 108 of the mature S1 subunit (Black et al., Science 240:656-659, 1988). This mutant strain has been shown to secrete a holotoxin analog of PTX, designated CRM3201, with reduced ADP-ribosyltransferase activity. In the present study, we evaluated the biochemical, biological, and immunoprotective activities of purified CRM3201. Assay of enzymatic activities showed that CRM3201 had 20 to 30% of the ADP-ribosyltransferase activity and 55 to 60% of the NAD glycohydrolase activity of native PTX. CRM3201, however, had only 2 to 6% of the activity of PTX in clustering CHO cells, promoting leukocytosis, inducing histamine sensitization, and potentiating an anaphylactic response to bovine serum albumin. In contrast, activities associated with the B oligomer (binding to fetuin, hemagglutination of goose erythrocytes, and lymphocyte mitogen activity) were comparable to those of native PTX. Injection of BALB/c mice with CRM3201 mixed with Al(OH)3 elicited high titers of antibody to PTX (as measured by enzyme-linked immunosorbent assay), which neutralized a leukocytosis-promoting dose of PTX in these mice and neutralized PTX in a CHO cell assay. Passive transfer of the anti-CRM3201 antibody protected 20-day-old Swiss-Webster mice against a lethal aerosol challenge with B. pertussis 18323. Active immunization with CRM3201 significantly reduced lung colonization in adult BALB/c mice with a B. pertussis respiratory infection. These results demonstrate (i) that the reduced ADP-ribosyltransferase activity of CRM3201 is associated with reductions in certain biological and toxic activities of PTX (the enzymatic and biological activities are not, however, totally concordant); (ii) that CRM3201 possesses a functional B oligomer; and (iii) that CRM3201 can induce toxin-neutralizing antibodies which protect mice

  7. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins.

    PubMed

    Fuhrmann, Gregor; Serio, Andrea; Mazo, Manuel; Nair, Rekha; Stevens, Molly M

    2015-05-10

    Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by >60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods. PMID:25483424

  8. Aspects of igneous activity significant to a repository at Yucca Mountain, Nevada

    SciTech Connect

    Krier, D. J.; Perry, F. V.

    2004-01-01

    Location, timing, volume, and eruptive style of post-Miocene volcanoes have defined the volcanic hazard significant to a proposed high-level radioactive waste (HLW) and spent nuclear fuel (SNF) repository at Yucca Mountain, Nevada, as a low-probability, high-consequence event. Examination of eruptive centers in the region that may be analogueues to possible future volcanic activity at Yucca Mountain have aided in defining and evaluating the consequence scenarios for intrusion into and eruption above a repository. The probability of a future event intersecting a repository at Yucca Mountain has a mean value of 1.7 x 10{sup -8} per year. This probability comes from the Probabilistic Volcanic Hazard Assessment (PVHA) completed in 1996 and updated to reflect change in repository layout. Since that time, magnetic anomalies representing potential buried volcanic centers have been identified fiom magnetic surveys; however these potential buried centers only slightly increase the probability of an event intersecting the repository. The proposed repository will be located in its central portion of Yucca Mountain at approximately 300m depth. The process for assessing performance of a repository at Yucca Mountain has identified two scenarios for igneous activity that, although having a very low probability of occurrence, could have a significant consequence should an igneous event occur. Either a dike swarm intersecting repository drifts containing waste packages, or a volcanic eruption through the repository could result in release of radioactive material to the accessible environment. Ongoing investigations are assessing the mechanisms and significance of the consequence scenarios. Lathrop Wells Cone ({approx}80,000 yrs), a key analogue for estimating potential future volcanic activity, is the youngest surface expression of apparent waning basaltic volcanism in the region. Cone internal structure, lavas, and ash-fall tephra have been examined to estimate eruptive volume

  9. Dioxin mediates downregulation of the reduced folate carrier transport activity via the arylhydrocarbon receptor signalling pathway

    SciTech Connect

    Halwachs, Sandra; Lakoma, Cathleen; Gebhardt, Rolf; Schaefer, Ingo; Seibel, Peter; Honscha, Walther

    2010-07-15

    Dioxins such as 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) are common environmental contaminants known to regulate several genes via activation of the transcription factor aryl hydrocarbon receptor (AhR) associated with the development of numerous adverse biological effects. However, comparatively little is known about the molecular mechanisms by which dioxins display their toxic effects in vertebrates. The 5' untranslated region of the hepatocellular Reduced folate carrier (Rfc1; Slc19a1) exhibits AhR binding sites termed dioxin responsive elements (DRE) that have as yet only been found in the promoter region of prototypical TCDD target genes. Rfc1 mediated transport of reduced folates and antifolate drugs such as methotrexate (MTX) plays an essential role in physiological folate homeostasis and MTX cancer chemotherapy. In order to determine whether this carrier represents a target gene of dioxins we have investigated the influence of TCDD on functional Rfc1 activity in rat liver. Pre-treatment of rats with TCDD significantly diminished hepatocellular Rfc1 uptake activity in a time- and dose-dependent manner. In further mechanistic studies we demonstrated that this reduction was due to TCDD-dependent activation of the AhR signalling pathway. We additionally showed that binding of the activated receptor to DRE motifs in the Rfc1 promoter resulted in downregulation of Rfc1 gene expression and reduced carrier protein levels. As downregulation of pivotal Rfc1 activity results in functional folate deficiency associated with an elevated risk of cardiovascular diseases or carcinogenesis, our results indicate that deregulation of this essential transport pathway represents a novel regulatory mechanism how dioxins display their toxic effects through the Ah receptor.

  10. T Lymphocyte Activation Threshold is Increased in Reduced Gravity

    NASA Technical Reports Server (NTRS)

    Adams, Charley L.; Gonzalez, M.; Sams, C. F.

    2000-01-01

    There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

  11. Textured bearing surface in artificial joints to reduce macrophage activation

    NASA Astrophysics Data System (ADS)

    Nakanishi, Yoshitaka; Nishi, Naoki; Chikaura, Hiroto; Nakashima, Yuta; Miura, Hiromasa; Higaki, Hidehiko; Mizuta, Hiroshi; Iwamoto, Yukihide; Fujiwara, Yukio; Komohara, Yoshihiro; Takeya, Motohiro

    2015-12-01

    Micro slurry-jet erosion has been proposed as a precision machining technique for the bearing surfaces of artificial joints in order to reduce the total amount of polyethylene wear and to enlarge the size of the wear debris. The micro slurry-jet erosion method is a wet blasting technique which uses alumina particles as the abrasive medium along with compressed air and water to create an ideal surface. Pin-on-disc wear tests with multidirectional sliding motion on the textured surface of a \\text{Co}-\\text{Cr}-\\text{Mo} alloy counterface for polyethylene resulted in both a reduction of wear as well as enlargement of the polyethylene debris size. In this study, primary human peripheral blood mononuclear phagocytes were incubated with the debris, and it was elucidated that the wear debris generated on the textured surface regulated secretion of the proinflammatory cytokines IL-6 and TNF-α, indicating a reduction in the induced tissue reaction and joint loosening.

  12. Clinical significance of serum protease-activated receptor-1 levels in gastric cancer patients

    PubMed Central

    TAS, FARUK; KARABULUT, SENEM; TASTEKIN, DIDEM; DURANYILDIZ, DERYA

    2016-01-01

    Protease-activated receptor-1 (PAR-1) has a significant role in the pathogenesis of various malignancies and its expression mainly affects the survivals of cancer patients. The aim of the present study was to determine the clinical significance of the serum concentrations of PAR-1 in patients with gastric carcinoma. A total of 63 pathologically confirmed gastric cancer patients were enrolled in this study, with a median age of 62 years. Serum PAR-1 concentrations were determined by the enzyme-linked immunosorbent assay method and no significant difference in the baseline serum PAR-1 concentrations was found between patients and normal controls (P=0.5). The investigated clinical variables, including patient age, gender, localization of lesion, histology, grade of pathology, disease stage and serum tumor markers (lactate dehydrogenase, carcinoembryonic antigen and carbohydrate antigen 19-9) were not correlated with serum PAR-1 levels (P>0.05). Furthermore, no association was identified between the serum PAR-1 level and chemotherapy responsiveness (P=0.43). Serum PAR-1 level also had no prognostic role for survival (P=0.27). In conclusion, the serum PAR-1 concentration has no diagnostic, predictive and prognostic values in gastric cancer patients. PMID:27073639

  13. Recent Progress of R&D Activities on Reduced Activation Ferritic/Martensitic Steels

    SciTech Connect

    Huang, Q.; Baluc, N.; Dai, Y.; Jitsukawa, S.; Kimura, A.; Konys, J.; Kurtz, Richard J.; Lindau, R.; Muroga, T.; Odette, George R.; Raj, B.; Stoller, Roger E.; Tan, L.; Tanigawa, Hiroyasu; Tavassoli, A,-A.F.; Yamamoto, Takuya; Wan, F.; Wu, Y.

    2013-01-03

    Several types of reduced activation ferritic/martensitic (RAFM) steel have been developed over the past 30 years in China, Europe, India, Japan, Russia and the USA for application in ITER TBM and future fusion DEMO and power reactors. The progress has been particularly important during the past few years with evaluation of mechanical porperties of these steels before and after irradiation and in contact with different cooling media. This paper presents recent RAFM steel results obtained in ITER partner countries in relation with different TBM and DEMO options

  14. Irradiation-induced grain growth in nanocrystalline reduced activation ferrite/martensite steel

    SciTech Connect

    Liu, W. B.; Chen, L. Q.; Zhang, C. Yang, Z. G.; Ji, Y. Z.; Zang, H.; Shen, T. L.

    2014-09-22

    In this work, we investigate the microstructure evolution of surface-nanocrystallized reduced activation ferrite/martensite steels upon high-dose helium ion irradiation (24.3 dpa). We report a significant irradiation-induced grain growth in the irradiated buried layer at a depth of 300–500 nm, rather than at the peak damage region (at a depth of ∼840 nm). This phenomenon can be explained by the thermal spike model: minimization of the grain boundary (GB) curvature resulting from atomic diffusion in the cascade center near GBs.

  15. Hepcidin bound to α2-macroglobulin reduces ferroportin-1 expression and enhances its activity at reducing serum iron levels.

    PubMed

    Huang, Michael Li-Hsuan; Austin, Christopher J D; Sari, Marie-Agnès; Rahmanto, Yohan Suryo; Ponka, Prem; Vyoral, Daniel; Richardson, Des R

    2013-08-30

    Hepcidin regulates iron metabolism by down-regulating ferroportin-1 (Fpn1). We demonstrated that hepcidin is complexed to the blood transport protein, α2-macroglobulin (α2M) (Peslova, G., Petrak, J., Kuzelova, K., Hrdy, I., Halada, P., Kuchel, P. W., Soe-Lin, S., Ponka, P., Sutak, R., Becker, E., Huang, M. L., Suryo Rahmanto, Y., Richardson, D. R., and Vyoral, D. (2009) Blood 113, 6225-6236). However, nothing is known about the mechanism of hepcidin binding to α2M or the effects of the α2M·hepcidin complex in vivo. We show that decreased Fpn1 expression can be mediated by hepcidin bound to native α2M and also, for the first time, hepcidin bound to methylamine-activated α2M (α2M-MA). Passage of high molecular weight α2M·hepcidin or α2M-MA·hepcidin complexes (≈725 kDa) through a Sephadex G-25 size exclusion column retained their ability to decrease Fpn1 expression. Further studies using ultrafiltration indicated that hepcidin binding to α2M and α2M-MA was labile, resulting in some release from the protein, and this may explain its urinary excretion. To determine whether α2M-MA·hepcidin is delivered to cells via the α2M receptor (Lrp1), we assessed α2M uptake and Fpn1 expression in Lrp1(-/-) and Lrp1(+/+) cells. Interestingly, α2M·hepcidin or α2M-MA·hepcidin demonstrated similar activities at decreasing Fpn1 expression in Lrp1(-/-) and Lrp1(+/+) cells, indicating that Lrp1 is not essential for Fpn1 regulation. In vivo, hepcidin bound to α2M or α2M-MA did not affect plasma clearance of α2M/α2M-MA. However, serum iron levels were reduced to a significantly greater extent in mice treated with α2M·hepcidin or α2M-MA·hepcidin relative to unbound hepcidin. This effect could be mediated by the ability of α2M or α2M-MA to retard kidney filtration of bound hepcidin, increasing its half-life. A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated α2M, hepcidin remains labile and available to down

  16. Nature experience reduces rumination and subgenual prefrontal cortex activation

    PubMed Central

    Bratman, Gregory N.; Hamilton, J. Paul; Hahn, Kevin S.; Daily, Gretchen C.; Gross, James J.

    2015-01-01

    Urbanization has many benefits, but it also is associated with increased levels of mental illness, including depression. It has been suggested that decreased nature experience may help to explain the link between urbanization and mental illness. This suggestion is supported by a growing body of correlational and experimental evidence, which raises a further question: what mechanism(s) link decreased nature experience to the development of mental illness? One such mechanism might be the impact of nature exposure on rumination, a maladaptive pattern of self-referential thought that is associated with heightened risk for depression and other mental illnesses. We show in healthy participants that a brief nature experience, a 90-min walk in a natural setting, decreases both self-reported rumination and neural activity in the subgenual prefrontal cortex (sgPFC), whereas a 90-min walk in an urban setting has no such effects on self-reported rumination or neural activity. In other studies, the sgPFC has been associated with a self-focused behavioral withdrawal linked to rumination in both depressed and healthy individuals. This study reveals a pathway by which nature experience may improve mental well-being and suggests that accessible natural areas within urban contexts may be a critical resource for mental health in our rapidly urbanizing world. PMID:26124129

  17. Nature experience reduces rumination and subgenual prefrontal cortex activation.

    PubMed

    Bratman, Gregory N; Hamilton, J Paul; Hahn, Kevin S; Daily, Gretchen C; Gross, James J

    2015-07-14

    Urbanization has many benefits, but it also is associated with increased levels of mental illness, including depression. It has been suggested that decreased nature experience may help to explain the link between urbanization and mental illness. This suggestion is supported by a growing body of correlational and experimental evidence, which raises a further question: what mechanism(s) link decreased nature experience to the development of mental illness? One such mechanism might be the impact of nature exposure on rumination, a maladaptive pattern of self-referential thought that is associated with heightened risk for depression and other mental illnesses. We show in healthy participants that a brief nature experience, a 90-min walk in a natural setting, decreases both self-reported rumination and neural activity in the subgenual prefrontal cortex (sgPFC), whereas a 90-min walk in an urban setting has no such effects on self-reported rumination or neural activity. In other studies, the sgPFC has been associated with a self-focused behavioral withdrawal linked to rumination in both depressed and healthy individuals. This study reveals a pathway by which nature experience may improve mental well-being and suggests that accessible natural areas within urban contexts may be a critical resource for mental health in our rapidly urbanizing world. PMID:26124129

  18. AIDing cancer treatment: Reducing AID activity via HSP90 inhibition.

    PubMed

    Rebhandl, Stefan; Geisberger, Roland

    2015-08-01

    The activation induced deaminase (AID) catalyses the two key events underlying humoral adaptive immunity: class switch recombination and somatic hypermutation of antibody genes in B lymphocytes. AID accomplishes this task by directly deaminating cytosines within the genomic immunoglobulin locus, thereby triggering a complex mutagenic process eventually leading to improved effector function of antibodies. However, it has long been noticed that AID can be aberrantly expressed in cancer and that its activity is not absolutely restricted to antibody genes, as substantial genome-wide off-target mutations have been observed, which contribute to tumorigenesis and clonal evolution of AID-expressing malignancies. In this issue of the European Journal of Immunology, Montamat-Sicotte et al. [Eur. J. Immunol. 2015. 45: 2365-2376] investigate the feasibility and efficacy of in vivo inhibition of AID with HSP90 inhibitors in a mouse model of B-cell leukemia and in vitro with a human breast cancer cell line, thereby demonstrating that cancer patients may benefit from preventing noncanonical AID functions. PMID:26151367

  19. Proliferative activity is a significant prognostic factor in male breast carcinoma.

    PubMed Central

    Pich, A.; Margaria, E.; Chiusa, L.

    1994-01-01

    The proliferative activity of male breast carcinoma has been investigated using the staining of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody against the proliferating cell nuclear antigen (PC10) and the monoclonal antibody MIB-1 in formalin-fixed, paraffin-embedded specimens from 27 primary male breast carcinomas at diagnosis. A significant correlation was found between survival and AgNOR counts (median of survival 77 months for cases with AgNOR/cell < or = 7.27 but 37 months only for cases with > 7.27 AgNOR/cell; P = 0.001), proliferating cell nuclear antigen scores (median of survival 73 months for cases with proliferating cell nuclear antigen < or = 18.25% versus 41 for cases with proliferating cell nuclear antigen > 18.25%; P = 0.013) and MIB-1 scores (median of survival 73 months for cases with MIB-1 scores < or = 23.5% versus 37 months for cases with MIB-1 scores > 23.5%; P = 0.01). Tumor histological grade was also correlated with prognosis (median of survival 72 months for grade 2 versus 33 months for grade 3 tumors; P = 0.01). Estrogen and progesterone receptors, immunohistochemically detected on paraffin-embedded sections, had no prognostic value. In the multivariate survival analysis, only AgNOR counts (P = 0.007) and tumor size (P = 0.003) had an independent prognostic significance. Our results indicate that methods for assessing the cell proliferation in routinely processed specimens offer significant prognostic information in male breast carcinoma. The finding, together with the lack of prognostic significance for estrogen receptors and progesterone receptors, suggests that male breast carcinoma is biologically different from female breast cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7519830

  20. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium.

    PubMed

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A S; Fernàndez-Busquets, Xavier

    2016-01-01

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses. PMID:27071342

  1. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium

    PubMed Central

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A. S.; Fernàndez-Busquets, Xavier

    2016-01-01

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses. PMID:27071342

  2. Modelling precipitate distribution in reduced-activation steels

    NASA Astrophysics Data System (ADS)

    Gaude-Fugarolas, D.; de Carlan, Y.

    2008-02-01

    The microstructure and carbide distribution in two commercial creep resistant, low-activation, martensitic alloys (F82H and JLF-1) have been modelled using a thermo-kinetic calculation package. The microstructures after manufacturing and after long unstrained thermal aging treatments (13 500 h) at various temperatures (250, 400 and 550 °C), considered to be representative of service temperatures, have been considered. In all cases, the calculated carbide size distributions match in order of magnitude experimental measurements, although the shape of the distribution differs. The obtained results are more accurate for alloy F82H than for alloy JLF-1. Nevertheless, this work shows that it is possible to obtain realistic estimates of the microstructure evolution of creep resistant alloys in long thermal ageing treatments at service-like temperatures.

  3. Analysing domestic activity to reduce household energy consumption.

    PubMed

    Fréjus, Myriam; Guibourdenche, Julien

    2012-01-01

    This paper presents our reflections on the issue of behavioral change according to energy conservation constraints and on the status of sustainability in the design of ambient interactive systems at home. We point out how ergonomics contributes to the study of human factors underlying energy consumption. Relating to situated cognition and human computer interaction, our approach relies both on the ergonomic evaluation of feedback consumption displays and on the modeling of domestic activities in order to identify household concerns in real settings. We present empirical results to illustrate this global approach. The results of those studies allow the design of interactive systems: informative and pedagogical systems as well as pervasive and adaptive ambient systems. In our approach, sustainability is taken into account as a design criterion, as security could be, whereas the main design purpose is to aid households in their daily life in order to build a "sustainable situation". PMID:22316779

  4. Immune Activation Reduces Sperm Quality in the Great Tit

    PubMed Central

    Losdat, Sylvain; Richner, Heinz; Blount, Jonathan D.; Helfenstein, Fabrice

    2011-01-01

    Mounting an immune response against pathogens incurs costs to organisms by its effects on important life-history traits, such as reproductive investment and survival. As shown recently, immune activation produces large amounts of reactive species and is suggested to induce oxidative stress. Sperm are highly susceptible to oxidative stress, which can negatively impact sperm function and ultimately male fertilizing efficiency. Here we address the question as to whether mounting an immune response affects sperm quality through the damaging effects of oxidative stress. It has been demonstrated recently in birds that carotenoid-based ornaments can be reliable signals of a male's ability to protect sperm from oxidative damage. In a full-factorial design, we immune-challenged great tit males while simultaneously increasing their vitamin E availability, and assessed the effect on sperm quality and oxidative damage. We conducted this experiment in a natural population and tested the males' response to the experimental treatment in relation to their carotenoid-based breast coloration, a condition-dependent trait. Immune activation induced a steeper decline in sperm swimming velocity, thus highlighting the potential costs of an induced immune response on sperm competitive ability and fertilizing efficiency. We found sperm oxidative damage to be negatively correlated with sperm swimming velocity. However, blood resistance to a free-radical attack (a measure of somatic antioxidant capacity) as well as plasma and sperm levels of oxidative damage (lipid peroxidation) remained unaffected, thus suggesting that the observed effect did not arise through oxidative stress. Towards the end of their breeding cycle, swimming velocity of sperm of more intensely colored males was higher, which has important implications for the evolution of mate choice and multiple mating in females because females may accrue both direct and indirect benefits by mating with males having better quality sperm

  5. Functional significance of complex fluctuations in brain activity: from resting state to cognitive neuroscience

    PubMed Central

    Papo, David

    2014-01-01

    Behavioral studies have shown that human cognition is characterized by properties such as temporal scale invariance, heavy-tailed non-Gaussian distributions, and long-range correlations at long time scales, suggesting models of how (non observable) components of cognition interact. On the other hand, results from functional neuroimaging studies show that complex scaling and intermittency may be generic spatio-temporal properties of the brain at rest. Somehow surprisingly, though, hardly ever have the neural correlates of cognition been studied at time scales comparable to those at which cognition shows scaling properties. Here, we analyze the meanings of scaling properties and the significance of their task-related modulations for cognitive neuroscience. It is proposed that cognitive processes can be framed in terms of complex generic properties of brain activity at rest and, ultimately, of functional equations, limiting distributions, symmetries, and possibly universality classes characterizing them. PMID:24966818

  6. Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

    PubMed Central

    Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

    2015-01-01

    Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

  7. Powered hip exoskeletons can reduce the user's hip and ankle muscle activations during walking.

    PubMed

    Lenzi, Tommaso; Carrozza, Maria Chiara; Agrawal, Sunil K

    2013-11-01

    In this paper, we study the human locomotor adaptation to the action of a powered exoskeleton providing assistive torque at the user's hip during walking. To this end, we propose a controller that provides the user's hip with a fraction of the nominal torque profile, adapted to the specific gait features of the user from Winter's reference data . The assistive controller has been implemented on the ALEX II exoskeleton and tested on ten healthy subjects. Experimental results show that when assisted by the exoskeleton, users can reduce the muscle effort compared to free walking. Despite providing assistance only to the hip joint, both hip and ankle muscles significantly reduced their activation, indicating a clear tradeoff between hip and ankle strategy to propel walking. PMID:23529105

  8. Nutritional significance of a rice bran concentrate with trypsin inhibitor activity.

    PubMed

    Maki, Z; Tashiro, M

    1983-06-01

    A rice bran protein concentrate (RBPC) was prepared from de-fatted rice bran by extraction with a 1% sodium chloride solution and by acetone-precipitation. This protein concentrate contained 45% protein, which was as good as casein in terms of protein quality being judged from the results of amino acid analysis. On the other hand, RBPC possessed the trypsin inhibitor activity corresponding to the complete inhibition of about 6 mg of bovine trypsin per 1 g of dry material. The activity was, however, completely destroyed by autoclaving RBPC for 30 min at 121 degrees C. In vitro digestion tests showed that RBPC was easily digested by pepsin but was resistant to the attack by trypsin, compared with autoclaved RBPC. Concerning in vivo digestion, however, there was no significant difference in apparent nitrogen digestibility between RBPC and the heated RBPC. In growth experiments with weanling rats fed a 10% level of protein diet, growth depression and the tendency of slight pancreatic hypertrophy were observed in rats receiving a RBPC diet. It is presumed that one of the reasons which explains these phenomena is the presence of trypsin inhibitor in RBPC. PMID:6619992

  9. Comparison of the activities of the lantibiotics nisin and lacticin 3147 against clinically significant mycobacteria.

    PubMed

    Carroll, James; Draper, Lorraine A; O'Connor, Paula M; Coffey, Aidan; Hill, Colin; Ross, R Paul; Cotter, Paul D; O'Mahony, Jim

    2010-08-01

    The aim of this study was to use the microtitre alamarBlue assay to investigate and compare the antimycobacterial potential of the lantibiotics nisin and lacticin 3147 against a representative cohort of clinically significant mycobacteria, i.e. Mycobacterium tuberculosis H37Ra, Mycobacterium avium subsp. paratuberculosis (MAP) ATCC 19698 and Mycobacterium kansasii CIT11/06. Lacticin 3147 displayed potent activity against all strains of mycobacteria, with MIC(90) values (lowest concentration of lantibiotic that prevented growth of >90% of the bacterial population) of 60 mg/L and 15 mg/L for M. kansasii and MAP, respectively. Lacticin 3147 was particularly effective against M. tuberculosis H37Ra, with a MIC(90) value of 7.5mg/L. Nisin, although inhibitory, was generally less potent against all strains of mycobacteria, with MIC(90) values of 60 mg/L for M. kansasii and >60 mg/L for MAP and M. tuberculosis H37Ra. Thus, lacticin 3147 is a potent antimycobacterial peptide that shows superior activity compared with nisin at physiological pH. PMID:20547041

  10. Lack of significant promoting activity by benzene in the rat liver model of carcinogenesis

    SciTech Connect

    Taningher, M.; Perrotta, A.; Malacarne, D.

    1995-08-01

    The promoting activity of benzene on rat liver carcinogenesis was investigated. The chemical was tested for its ability to enhance the growth of preneoplastic foci, as detected by gamma-glutamyl transpeptidase (GGT) staining in diethylnitrosamine (DENA) initiated hepatocytes. Two weeks after receiving a single ip dose of 200 mg/kg DENA, F344 rats were given daily oral doses of 400 mg/kg benzene (5 d/wk) for 6 wk. At wk 3 after the experiment began, all animals underwent partial hepatectomy, and at wk 8 were sacrificed. Following benzene treatment, no variation in the liver/body weight ratio was observed. After scoring of foci in liver slides, no significant difference in foci number and area could be observed between rats treated with DENA plus benzene and rats treated with DENA alone. Practically no foci were observed in the liver of rats treated only with benzene. The lack of benzene promoting activity in the liver model is discussed. 28 refs., 1 fig., 1 tab.

  11. Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

    PubMed

    Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-01-01

    This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity. PMID:25394827

  12. Simulated microgravity alters multipotential differentiation of rat mesenchymal stem cells in association with reduced telomerase activity

    NASA Astrophysics Data System (ADS)

    Sun, Lianwen; Gan, Bo; Fan, Yubo; Xie, Tian; Hu, Qinghua; Zhuang, Fengyuan

    Microgravity is one of the most important characteristics in space flight. Exposure to microgravity results in extensive physiological changes in humans. Bone loss is one of the changes with serious consequences; however, the mechanism retains unclear. As the origin of osteoprogenitors, mesenchymal stem cells (MSCs) may play an important role in it. After cultured under simulated microgravity (in a rotary cell culture system, RCCS), MSCs were stained using oil red O to identify adipocytes. The mRNA level of bone morphogenetic protein (BMP)-2 and peroxisome proliferators-activated receptor (PPAR) γ2 was determined by RT-PCR. Otherwise, MSCs were induced to osteogenic differentiation after microgravity culture, and then the activity of alkaline phosphatase (ALP) was determined by PNPP and the content of osteocalcin (OC) by ELISA. Furthermore, the telomerase activity in MSCs was measured by TRAP. The results showed that simulated microgravity inhibited osteoblastic differentiation and induced adipogenic differentiation accompanied by the change of gene expression of BMP-2 and PPARγ2 in MSCs. Meanwhile, the telomerase activity decreased significantly in MSCs under simulated microgravity. The reduced bone formation in space flight may partly be due to the altered potential differentiation of MSCs associated with telomerase activity which plays a key role in regulating the lifespan of cell proliferation and differentiation. Therefore, telomerase activation/replacement may act as a potential countermeasure for microgravity-induced bone loss.

  13. Reduced cerebral blood flow with orthostasis precedes hypocapnic hyperpnea, sympathetic activation, and postural tachycardia syndrome.

    PubMed

    Del Pozzi, Andrew T; Schwartz, Christopher E; Tewari, Deepali; Medow, Marvin S; Stewart, Julian M

    2014-06-01

    Hyperventilation and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. On the basis of our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects with 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis before blood pressure recovery; central blood volume and mean arterial pressure were reduced (P<0.025), resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05) when compared with controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS (P<0.01) and inversely proportional to end tidal CO2 and resulted in an increase in heart rate (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia, and a statistically significant increase in blood pressure. PMID:24711524

  14. REDUCED CEREBRAL BLOOD FLOW WITH ORTHOSTASIS PRECEDES HYPOCAPNIC HYPERPNEA, SYMPATHETIC ACTIVATION AND POTS

    PubMed Central

    Del Pozzi, Andrew T.; Schwartz, Christopher E.; Tewari, Deepali; Medow, Marvin S.; Stewart, Julian M.

    2014-01-01

    Hyperventilation, and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. Based on our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects to 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis prior to BP recovery; central blood volume and mean arterial pressure were reduced (P<0.025) resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05), compared to controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS, (P<0.01), and inversely proportional to end tidal CO2 and resulted in an increase in heart rate, (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia and a statistically significant increase in blood pressure. PMID:24711524

  15. Unfolded protein response activation reduces secretion and extracellular aggregation of amyloidogenic immunoglobulin light chain

    PubMed Central

    Cooley, Christina B.; Ryno, Lisa M.; Plate, Lars; Morgan, Gareth J.; Hulleman, John D.; Kelly, Jeffery W.; Wiseman, R. Luke

    2014-01-01

    Light-chain amyloidosis (AL) is a degenerative disease characterized by the extracellular aggregation of a destabilized amyloidogenic Ig light chain (LC) secreted from a clonally expanded plasma cell. Current treatments for AL revolve around ablating the cancer plasma cell population using chemotherapy regimens. Unfortunately, this approach is limited to the ∼70% of patients who do not exhibit significant organ proteotoxicity and can tolerate chemotherapy. Thus, identifying new therapeutic strategies to alleviate LC organ proteotoxicity should allow AL patients with significant cardiac and/or renal involvement to subsequently tolerate established chemotherapy treatments. Using a small-molecule screening approach, the unfolded protein response (UPR) was identified as a cellular signaling pathway whose activation selectively attenuates secretion of amyloidogenic LC, while not affecting secretion of a nonamyloidogenic LC. Activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the absence of stress recapitulates the selective decrease in amyloidogenic LC secretion by remodeling the endoplasmic reticulum proteostasis network. Stress-independent activation of XBP1s, or especially ATF6, also attenuates extracellular aggregation of amyloidogenic LC into soluble aggregates. Collectively, our results show that stress-independent activation of these adaptive UPR transcription factors offers a therapeutic strategy to reduce proteotoxicity associated with LC aggregation. PMID:25157167

  16. Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

    PubMed

    Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

    2015-07-01

    Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had

  17. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance.

    PubMed

    Yajima, Hiroaki; Ikeshima, Emiko; Shiraki, Maho; Kanaya, Tomoka; Fujiwara, Daisuke; Odai, Hideharu; Tsuboyama-Kasaoka, Nobuyo; Ezaki, Osamu; Oikawa, Shinichi; Kondo, Keiji

    2004-08-01

    The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of fibrate drugs and the therapeutic benefits of the thiazolidinedione drugs are due to their activation of PPARalpha and -gamma, respectively. In this study, isohumulones, the bitter compounds derived from hops that are present in beer, were found to activate PPARalpha and -gamma in transient co-transfection studies. Among the three major isohumulone homologs, isohumulone and isocohumulone were found to activate PPARalpha and -gamma. Diabetic KK-Ay mice that were treated with isohumulones (isohumulone and isocohumulone) showed reduced plasma glucose, triglyceride, and free fatty acid levels (65.3, 62.6, and 73.1%, respectively, for isohumulone); similar reductions were found following treatment with the thiazolidinedione drug, pioglitazone. Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10.6% increase versus control group). C57BL/6N mice fed a high fat diet that were treated with isohumulones showed improved glucose tolerance and reduced insulin resistance. Furthermore, these animals showed increased liver fatty acid oxidation and a decrease in size and an increase in apoptosis of their hypertrophic adipocytes. A double-blind, placebo-controlled pilot study for studying the effect of isohumulones on diabetes suggested that isohumulones significantly decreased blood glucose and hemoglobin A1c levels after 8 weeks (by 10.1 and 6.4%, respectively, versus week 0). These results suggest that isohumulones can improve insulin sensitivity in high fat diet-fed mice with insulin resistance and in patients with type 2 diabetes. PMID:15178687

  18. Reduced Activity Restriction Buffers the Relations Between Chronic Stress and Sympathetic Nervous System Activation

    PubMed Central

    2014-01-01

    Objectives. Caregivers of dementia patients are at risk for developing cardiovascular disease (CVD), and this risk increases the longer they provide care. Greater perceptions that caregiving restricts social/recreational activities (i.e., activity restriction [AR]) has been associated with poorer health, and AR may exacerbate the relations between stress and health outcomes. The current study examined the interactive role of greater exposure to stress and increased AR on plasma catecholamine (CAT) levels: norepinephrine (NE) and epinephrine (EPI). Method. A total of 84 dementia caregivers completed a standard assessment battery, and a nurse collected blood, which was assayed for NE and EPI. Separate regressions for NE and EPI were used to determine whether the relations between years caregiving and CATs were greater in those with high versus low AR. Results. A significant interaction was found between years caregiving and AR in predicting resting EPI (p = .032) but not resting NE (p = .103). Post hoc analyses indicated that years caregiving was significantly associated with EPI when AR was high (p = .008) but not when AR was low (p = .799). Additionally, years caregiving was not significantly associated with NE when AR was high or low. Discussion. The subjective experience of AR can play an important role in determining risk for detrimental physical health outcomes, particularly CVD risk. PMID:23685924

  19. Reducing infection in chronic leg ulcers with an activated carbon cloth dressing.

    PubMed

    Murphy, Nina

    2016-06-23

    Zorflex is a new type of antimicrobial dressing composed of 100% activated carbon cloth. It attracts and binds bacteria to its surface, enabling them to be safely removed at dressing change. It has no reported toxic effects and can be used on either a short-or long-term basis. This article describes 4 case studies in which patients with recalcitrant chronic venous leg ulcers that were prone to recurrent infection were treated with the activated carbon cloth dressing. All of the wounds had failed to respond to antimicrobial dressings containing silver, iodine or polyhexamethylene biguanide (PHMB), and were heavily exuding and painful. In all cases, the signs of infection reduced significantly within 4 weeks, resulting in good patient outcomes. PMID:27345081

  20. A Forecast of Reduced Solar Activity and Its Implications for NASA

    NASA Technical Reports Server (NTRS)

    Schatten, Kenneth; Franz, Heather

    2005-01-01

    The "Solar Dynamo" method of solar activity forecasting is reviewed. Known generically as a 'precursor" method, insofar as it uses observations which precede solar activity generation, this method now uses the Solar Dynamo Amplitude (SODA) Index to estimate future long-term solar activity. The peak amplitude of the next solar cycle (#24), is estimated at roughly 124 in terms of smoothed F10.7 Radio Flux and 74 in terms of the older, more traditional smoothed international or Zurich Sunspot number (Ri or Rz). These values are significantly smaller than the amplitudes of recent solar cycles. Levels of activity stay large for about four years near the peak in smoothed activity, which is estimated to occur near the 2012 timeflame. Confidence is added to the prediction of low activity by numerous examinations of the Sun s weakened polar field. Direct measurements are obtained by the Mount Wilson Solar Observatory and the Wilcox Solar Observatory. Further support is obtained by examining the Sun s polar faculae (bright features), the shape of coronal soft X-ray "holes," and the shape of the "source surface" - a calculated coronal feature which maps the large scale structure of the Sun s field. These features do not show the characteristics of well-formed polar coronal holes associated with typical solar minima. They show stunted polar field levels, which are thought to result in stunted levels of solar activity during solar cycle #24. The reduced levels of solar activity would have concomitant effects upon the space environment in which satellites orbit. In particular, the largest influences would affect orbit determination of satellites in LEO (Low Earth Orbit), based upon the altered thermospheric and exospheric densities. A decrease in solar activity would result in smaller satellite decay rates, as well as fewer large solar events that can destroy satellite electronic functions. Other effects of reduced solar activity upon the space environment include enhanced

  1. Activation of the chicken gonadotropin-inhibitory hormone receptor reduces gonadotropin releasing hormone receptor signaling.

    PubMed

    Shimizu, Mamiko; Bédécarrats, Grégoy Y

    2010-06-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic peptide from the RFamide peptide family that has been identified in multiple avian species. Although GnIH has clearly been shown to reduce LH release from the anterior pituitary gland, its mechanism of action remains to be determined. The overall objectives of this study were (1) to characterize the GnIH receptor (GnIH-R) signaling pathway, (2) to evaluate potential interactions with gonadotropin releasing hormone type III receptor (GnRH-R-III) signaling, and (3) to determine the molecular mechanisms by which GnIH and GnRH regulate pituitary gonadotrope function during a reproductive cycle in the chicken. Using real-time PCR, we showed that in the chicken pituitary gland, GnIH-R mRNA levels fluctuate in an opposite manner to GnRH-R-III, with higher and lower levels observed during inactive and active reproductive stages, respectively. We demonstrated that the chicken GnIH-R signals by inhibiting adenylyl cyclase cAMP production, most likely by coupling to G(alphai). We also showed that this inhibition is sufficient to significantly reduce GnRH-induced cAMP responsive element (CRE) activation in a dose-dependent manner, and that the ratio of GnRH/GnIH receptors is a significant factor. We propose that in avian species, sexual maturation is characterized by a change in GnIH/GnRH receptor ratio, resulting in a switch in pituitary sensitivity from inhibitory (involving GnIH) to stimulatory (involving GnRH). In turn, decreasing GnIH-R signaling, combined with increasing GnRH-R-III signaling, results in significant increases in CRE activation, possibly initiating gonadotropin synthesis. PMID:20350548

  2. A practical cooling strategy for reducing the physiological strain associated with firefighting activity in the heat.

    PubMed

    Barr, D; Gregson, W; Sutton, L; Reilly, T

    2009-04-01

    The aim of this study was to establish whether a practical cooling strategy reduces the physiological strain during simulated firefighting activity in the heat. On two separate occasions under high ambient temperatures (49.6 +/- 1.8 degrees C, relative humidity (RH) 13 +/- 2%), nine male firefighters wearing protective clothing completed two 20-min bouts of treadmill walking (5 km/h, 7.5% gradient) separated by a 15-min recovery period, during which firefighters were either cooled (cool) via application of an ice vest and hand and forearm water immersion ( approximately 19 degrees C) or remained seated without cooling (control). There was no significant difference between trials in any of the dependent variables during the first bout of exercise. Core body temperature (37.72 +/- 0.34 vs. 38.21 +/- 0.17 degrees C), heart rate (HR) (81 +/- 9 vs. 96 +/- 17 beats/min) and mean skin temperature (31.22 +/- 1.04 degrees C vs. 33.31 +/- 1 degrees C) were significantly lower following the recovery period in cool compared with control (p < 0.05). Core body temperature remained consistently lower (0.49 +/- 0.02 degrees C; p < 0.01) throughout the second bout of activity in cool compared to control. Mean skin temperature, HR and thermal sensation were significantly lower during bout 2 in cool compared with control (p < 0.05). It is concluded that this practical cooling strategy is effective at reducing the physiological strain associated with demanding firefighting activity under high ambient temperatures. PMID:19401892

  3. Physiological Sleep Propensity Might Be Unaffected by Significant Variations in Self-Reported Well-Being, Activity, and Mood.

    PubMed

    Putilov, Arcady A

    2015-01-01

    Background and Objective. Depressive state is often associated with such physical symptoms as general weakness, fatigue, tiredness, slowness, reduced activity, low energy, and sleepiness. The involvement of the sleep-wake regulating mechanisms has been proposed as one of the plausible explanations of this association. Both physical depressive symptoms and increased physiological sleep propensity can result from disordered and insufficient sleep. In order to avoid the influence of disordered and insufficient sleep, daytime and nighttime sleepiness were tested in winter depression characterized by normal night sleep duration and architecture. Materials and Methods. A total sample consisted of 6 healthy controls and 9 patients suffered from depression in the previous winter season. Sleep latency was determined across 5 daytime and 4 nighttime 20-min attempts to nap in summer as well as in winter before and after a week of 2-hour evening treatment with bright light. Results and Conclusions. Patients self-reported abnormally lowered well-being, activity, and mood only in winter before the treatment. Physiological sleep propensity was neither abnormal nor linked to significant changes in well-being, activity, and mood following the treatment and change in season. It seems unlikely that the mechanisms regulating the sleep-wake cycle contributed to the development of the physical depressive symptoms. PMID:26294978

  4. Physiological Sleep Propensity Might Be Unaffected by Significant Variations in Self-Reported Well-Being, Activity, and Mood

    PubMed Central

    Putilov, Arcady A.

    2015-01-01

    Background and Objective. Depressive state is often associated with such physical symptoms as general weakness, fatigue, tiredness, slowness, reduced activity, low energy, and sleepiness. The involvement of the sleep-wake regulating mechanisms has been proposed as one of the plausible explanations of this association. Both physical depressive symptoms and increased physiological sleep propensity can result from disordered and insufficient sleep. In order to avoid the influence of disordered and insufficient sleep, daytime and nighttime sleepiness were tested in winter depression characterized by normal night sleep duration and architecture. Materials and Methods. A total sample consisted of 6 healthy controls and 9 patients suffered from depression in the previous winter season. Sleep latency was determined across 5 daytime and 4 nighttime 20-min attempts to nap in summer as well as in winter before and after a week of 2-hour evening treatment with bright light. Results and Conclusions. Patients self-reported abnormally lowered well-being, activity, and mood only in winter before the treatment. Physiological sleep propensity was neither abnormal nor linked to significant changes in well-being, activity, and mood following the treatment and change in season. It seems unlikely that the mechanisms regulating the sleep-wake cycle contributed to the development of the physical depressive symptoms. PMID:26294978

  5. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

    PubMed Central

    Liu, Mei; Gill, Jason J.; Young, Ry; Summer, Elizabeth J.

    2015-01-01

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment. PMID:26349678

  6. Mex3c mutation reduces adiposity partially through increasing physical activity.

    PubMed

    Han, Changjie; Jiao, Yan; Zhao, Qingguo; Lu, Baisong

    2014-06-01

    MEX3C is an RNA-binding protein with unknown physiological function. We have recently reported that a Mex3c mutation in mice causes growth retardation and reduced adiposity, but how adiposity is reduced remains unclear. Herein, we show that homozygous Mex3c gene trap mice have increased physical activity. The Mex3c mutation consistently conferred full protection from diet-induced obesity, hyperglycemia, insulin resistance, hyperlipidemia, and hepatic steatosis. In ob/ob mice with leptin deficiency, the Mex3c mutation also increased physical activity and improved glucose and lipid profiles. Expressing cre in the neurons of Mex3c gene trap mice, an attempt to partially restoring neuronal Mex3c expression, significantly increased white adipose tissue deposition, but had no effects on body length. Our data suggest that one way in which Mex3c regulates adiposity is through controlling physical activity, and that neuronal Mex3c expression could play an important role in this process. PMID:24741071

  7. Renal adenylate cyclase assay for biologically active parathyroid hormone: clinical utility and physiological significance.

    PubMed

    Auf'mkolk, B; Hesch, R D

    1986-01-01

    The stimulation of cyclic AMP production by human renal cortical membranes in the presence of the GTP analogue 5'-guanylimidodiphosphate and a calcium chelator represents a homologous assay system for the evaluation of biologically active parathyroid hormone (bioPTH) in human serum. Bioactive PTH was raised above normal (normal range: undetectable to 4.6 pmol human PTH(1-34) per 1) in 13/17 (76%) patients with primary hyperparathyroidism, in 5/6 (83%) patients with surgically proven hyperparathyroidism secondary to chronic renal failure, in 4/5 (80%) patients with hyperparathyroidism secondary to hypocalcaemia, in all three patients with pseudohypoparathyroidism, in 5/17 (29%) patients with osteoporosis and in 1/9 (11%) patients with renal stones and/or hypercalciuria. Bioactive PTH correlated positively with immunoreactive PTH (iPTH) measured with a radioimmunoassay predominantly recognizing the middle- and carboxyl-terminal region of the PTH molecule (r = 0.503, P less than 0.001). A positive correlation (r = 0.572, P less than 0.05) was found between values of serum calcium and bioPTH in the group with primary hyperparathyroidism. Immunoreactive PTH did not correlate significantly with calcium in this group. In the other patients except those who had chronic renal failure, a negative correlation between serum calcium and both bioPTH and iPTH was observed (P less than 0.01). When alkaline phosphatase was compared with bioPTH in all patients, the correlation was positive (r = 0.390, P less than 0.01); no significant correlation existed between iPTH and alkaline phosphatase in the patients studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3944539

  8. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  9. Arterial chemoreceptor activation reduces the activity of parapyramidal serotonergic neurons in rats.

    PubMed

    Takakura, A C; Moreira, T S

    2013-05-01

    The parapyramidal (ppy) region targets primarily the intermediolateral cell column and is probably involved in breathing and thermoregulation. In the present study, we tested whether ppy serotonergic neurons respond to activation of central and peripheral chemoreceptors. Bulbospinal ppy neurons (n=30) were recorded extracellularly along with the phrenic nerve activity in urethane/α-chloralose-anesthetized, paralyzed, intact (n=7) or carotid body denervated (n=6) male Wistar rats. In intact animals, most of the ppy neurons were inhibited by hypoxia (n=14 of 19) (8% O2, 30s) (1.5 ± 0.03 vs. control: 2.4 ± 0.2 Hz) or hypercapnia (n=15 of 19) (10% CO2) (1.7 ± 0.1 vs. control: 2.2 ± 0.2 Hz), although some neurons were insensitive to hypoxia (n=3 of 19) or hypercapnia (n=4 of 19). Very few neurons (n=2 of 19) were activated after hypoxia, but not after hypercapnia. In carotid body denervated rats, all the 5HT-ppy neurons (n=11) were insensitive to hypercapnia (2.1 ± 0.1 vs. control: 2.3 ± 0.09 Hz). Biotinamide-labeled cells that were recovered after histochemistry were located in the ppy region. Most labeled cells (90%) showed strong tryptophan hydroxylase immunocytochemical reactivity, indicating that they were serotonergic. The present data reveal that peripheral chemoreceptors reduce the activity of the serotonergic premotor neurons located in the ppy region. It is plausible that the serotonergic neurons of the ppy region could conceivably regulate breathing automaticity and be involved in autonomic regulation. PMID:23403178

  10. Significance of redox-active cysteines in human FAD synthase isoform 2.

    PubMed

    Miccolis, Angelica; Galluccio, Michele; Nitride, Chiara; Giancaspero, Teresa Anna; Ferranti, Pasquale; Iametti, Stefania; Indiveri, Cesare; Bonomi, Francesco; Barile, Maria

    2014-12-01

    FAD synthase (FMN:ATP adenylyl transferase, FMNAT or FADS, EC 2.7.7.2) is the last enzyme in the pathway converting riboflavin into FAD. In humans, FADS is localized in different subcellular compartments and exists in different isoforms. Isoform 2 (490-amino acids) is organized in two domains: the 3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase domain, that is the FAD-forming catalytic domain, and one resembling a molybdopterin-binding (MPTb) domain, with a hypothetical regulatory role. hFADS2 contains ten Cys residues, seven of which located in the PAPS reductase domain, with a possible involvement either in FAD synthesis or in FAD delivery to cognate apo-flavoproteins. A homology model of the PAPS reductase domain of hFADS2 revealed a co-ordinated network among the Cys residues in this domain. In this model, C312 and C303 are very close to the flavin substrate, consistent with a significantly lowered FAD synthesis rate in C303A and C312A mutants. FAD synthesis is also inhibited by thiol-blocking reagents, suggesting the involvement of free cysteines in the hFADS2 catalytic cycle. Mass spectrometry measurements and titration with thiol reagents on wt hFADS2 and on several individual cysteine/alanine mutants allowed us to detect two stably reduced cysteines (C139 and C241, one for each protein domain), two stable disulfide bridges (C399-C402, C303-C312, both in the PAPS domain), and two unstable disulfides (C39-C50; C440-C464). Whereas the C39-C50 unstable disulfide is located in the MPTb domain and appears to have no catalytic relevance, a cysteine-based redox switch may involve formation and breakdown of a disulfide between C440 and C464 in the PAPS domain. PMID:25135855

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    SciTech Connect

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. From meatless Mondays to meatless Sundays: motivations for meat reduction among vegetarians and semi-vegetarians who mildly or significantly reduce their meat intake.

    PubMed

    De Backer, Charlotte J S; Hudders, Liselot

    2014-01-01

    This study explores vegetarians' and semi-vegetarians' motives for reducing their meat intake. Participants are categorized as vegetarians (remove all meat from their diet); semi-vegetarians (significantly reduce meat intake: at least three days a week); or light semi-vegetarians (mildly reduce meat intake: once or twice a week). Most differences appear between vegetarians and both groups of semi-vegetarians. Animal-rights and ecological concerns, together with taste preferences, predict vegetarianism, while an increase in health motives increases the odds of being semi-vegetarian. Even within each group, subgroups with different motives appear, and it is recommended that future researchers pay more attention to these differences. PMID:25357269

  13. Latent myostatin has significant activity and this activity is controlled more efficiently by WFIKKN1 than by WFIKKN2.

    PubMed

    Szláma, György; Trexler, Mária; Patthy, László

    2013-08-01

    Myostatin, a negative regulator of skeletal muscle growth, is produced from myostatin precursor by multiple steps of proteolytic processing. After cleavage by a furin-type protease, the propeptide and growth factor domains remain associated, forming a noncovalent complex, the latent myostatin complex. Mature myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases. Here, we show that, in reporter assays, latent myostatin preparations have significant myostatin activity, as the noncovalent complex dissociates at an appreciable rate, and both mature and semilatent myostatin (a complex in which the dimeric growth factor domain interacts with only one molecule of myostatin propeptide) bind to myostatin receptor. The interaction of myostatin receptor with semilatent myostatin is efficiently blocked by WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 or growth and differentiation factor-associated serum protein 2 (WFIKKN1), a large extracellular multidomain protein that binds both mature myostatin and myostatin propeptide [Kondás et al. (2008) J Biol Chem 283, 23677-23684]. Interestingly, the paralogous protein WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 or growth and differentiation factor-associated serum protein 1 (WFIKKN2) was less efficient than WFIKKN1 as an antagonist of the interactions of myostatin receptor with semilatent myostatin. Our studies have shown that this difference is attributable to the fact that only WFIKKN1 has affinity for the propeptide domain, and this interaction increases its potency in suppressing the receptor-binding activity of semilatent myostatin. As the interaction of WFIKKN1 with various forms of myostatin permits tighter control of myostatin activity until myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases, WFIKKN1 may have greater potential as an antimyostatic agent than WFIKKN2. PMID:23829672

  14. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase.

    PubMed

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  15. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase

    PubMed Central

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  16. A Plasminogen Activator Inhibitor-1 Inhibitor Reduces Airway Remodeling in a Murine Model of Chronic Asthma

    PubMed Central

    Lee, Sun H.; Eren, Mesut; Vaughan, Douglas E.; Schleimer, Robert P.

    2012-01-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  17. A plasminogen activator inhibitor-1 inhibitor reduces airway remodeling in a murine model of chronic asthma.

    PubMed

    Lee, Sun H; Eren, Mesut; Vaughan, Douglas E; Schleimer, Robert P; Cho, Seong H

    2012-06-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  18. Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity

    PubMed Central

    2013-01-01

    Background Recently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF. Methods Of the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann–Whitney U-test and the chi-square test. Results Of the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively). Conclusions A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity. PMID:23663265

  19. The Novel Antitubulin Agent TR-764 Strongly Reduces Tumor Vasculature and Inhibits HIF-1α Activation.

    PubMed

    Porcù, Elena; Persano, Luca; Ronca, Roberto; Mitola, Stefania; Bortolozzi, Roberta; Romagnoli, Romeo; Oliva, Paola; Basso, Giuseppe; Viola, Giampietro

    2016-01-01

    Tubulin binding agents (TBAs) are commonly used in cancer therapy as antimitotics. It has been described that TBAs, like combretastatin A-4 (CA-4), present also antivascular activity and among its derivatives we identified TR-764 as a new inhibitor of tubulin polymerization, based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene molecular skeleton. The antiangiogenic activity of TR-764 (1-10 nM) was tested in vitro on human umbilical endothelial cells (HUVECs), and in vivo, on the chick embryo chorioallantoic membrane (CAM) and two murine tumor models. TR-764 binding to tubulin triggers cytoskeleton rearrangement without affecting cell cycle and viability. It leads to capillary tube disruption, increased cell permeability, and cell motility reduction. Moreover it disrupts adherens junctions and focal adhesions, through mechanisms involving VE-cadherin/β-catenin and FAK/Src. Importantly, TR-764 is active in hypoxic conditions significantly reducing HIF-1α. In vivo TR-764 (1-100 pmol/egg) remarkably blocks the bFGF proangiogenic activity on CAM and shows a stronger reduction of tumor mass and microvascular density both in murine syngeneic and xenograft tumor models, compared to the lead compound CA-4P. Altogether, our results indicate that TR-764 is a novel TBA with strong potential as both antivascular and antitumor molecule that could improve the common anticancer therapies, by overcoming hypoxia-induced resistance mechanisms. PMID:27292568

  20. Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice

    PubMed Central

    Ottenhoff, Roelof; van Roomen, Cindy P. A. A.; Herrera Moro, Daniela; Claessen, Nike; Vinueza Veloz, María Fernanda; Zhou, Kuikui; Lin, Zhanmin; Mirzaian, Mina; Boot, Rolf G.; De Zeeuw, Chris I.; Overkleeft, Herman S.; Yildiz, Yildiz; Aerts, Johannes M. F. G.

    2015-01-01

    The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC. PMID:26275242

  1. The Novel Antitubulin Agent TR-764 Strongly Reduces Tumor Vasculature and Inhibits HIF-1α Activation

    PubMed Central

    Porcù, Elena; Persano, Luca; Ronca, Roberto; Mitola, Stefania; Bortolozzi, Roberta; Romagnoli, Romeo; Oliva, Paola; Basso, Giuseppe; Viola, Giampietro

    2016-01-01

    Tubulin binding agents (TBAs) are commonly used in cancer therapy as antimitotics. It has been described that TBAs, like combretastatin A-4 (CA-4), present also antivascular activity and among its derivatives we identified TR-764 as a new inhibitor of tubulin polymerization, based on the 2-(alkoxycarbonyl)-3-(3′,4′,5′-trimethoxyanilino)benzo[b]thiophene molecular skeleton. The antiangiogenic activity of TR-764 (1–10 nM) was tested in vitro on human umbilical endothelial cells (HUVECs), and in vivo, on the chick embryo chorioallantoic membrane (CAM) and two murine tumor models. TR-764 binding to tubulin triggers cytoskeleton rearrangement without affecting cell cycle and viability. It leads to capillary tube disruption, increased cell permeability, and cell motility reduction. Moreover it disrupts adherens junctions and focal adhesions, through mechanisms involving VE-cadherin/β-catenin and FAK/Src. Importantly, TR-764 is active in hypoxic conditions significantly reducing HIF-1α. In vivo TR-764 (1–100 pmol/egg) remarkably blocks the bFGF proangiogenic activity on CAM and shows a stronger reduction of tumor mass and microvascular density both in murine syngeneic and xenograft tumor models, compared to the lead compound CA-4P. Altogether, our results indicate that TR-764 is a novel TBA with strong potential as both antivascular and antitumor molecule that could improve the common anticancer therapies, by overcoming hypoxia-induced resistance mechanisms. PMID:27292568

  2. Circuit formation and function in the olfactory bulb of mice with reduced spontaneous afferent activity.

    PubMed

    Lorenzon, Paolo; Redolfi, Nelly; Podolsky, Michael J; Zamparo, Ilaria; Franchi, Sira Angela; Pietra, Gianluca; Boccaccio, Anna; Menini, Anna; Murthy, Venkatesh N; Lodovichi, Claudia

    2015-01-01

    The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i.e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing. PMID:25568110

  3. Significance of Plasma Dopamine β-Hydroxylase Activity as an Index of Sympathetic Neuronal Function

    PubMed Central

    Reid, John L.; Kopin, Irwin J.

    1974-01-01

    Plasma norepinephrine and dopamine β-hydroxylase (EC 1.14.17.1) activity were measured in rats. Adrenergic neuron blockade with bretylium for 4 hr and ganglion blockade with chlorisondamine for 72 hr lowered plasma norepinephrine. Neither treatment altered plasma dopamine β-hydroxylase activity. Phenoxybenzamine for up to 48 hr markedly raised plasma norepinephrine and transiently lowered plasma dopamine β-hydroxylase at 24 hr. Prolonged pharmacological modification of sympathetic nervous activity and plasma norepinephrine were not attended by parallel changes in circulating dopamine β-hydroxylase activity. Plasma dopamine β-hydroxylase activity does not appear to be a sensitive index of prolonged alterations in sympathetic neural activity. Norepinephrine in plasma, however, appears to reflect sensitively and accurately the rate of release of the neurotransmitter. PMID:4530990

  4. Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity

    PubMed Central

    2012-01-01

    Background Primary osteoporosis is a rare childhood-onset skeletal condition whose pathogenesis has been largely unknown. We have previously shown that primary osteoporosis can be caused by heterozygous missense mutations in the Low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the role of LRP5 is further investigated here. Methods LRP5 was analyzed in 18 otherwise healthy children and adolescents who had evidence of osteoporosis (manifested as reduced bone mineral density i.e. BMD, recurrent peripheral fractures and/or vertebral compression fractures) but who lacked the clinical features of osteogenesis imperfecta (OI) or other known syndromes linked to low BMD. Also 51 controls were analyzed. Methods used in the genetic analyses included direct sequencing and multiplex ligation-dependent probe amplification (MLPA). In vitro studies were performed using luciferase assay and quantitative real-time polymerase chain reaction (qPCR) to examine the effect of two novel and three previously identified mutations on the activity of canonical Wnt signaling and on expression of tryptophan hydroxylase 1 (Tph1) and 5-hydroxytryptamine (5-Htr1b). Results Two novel LRP5 mutations (c.3446 T > A; p.L1149Q and c.3553 G > A; p.G1185R) were identified in two patients and their affected family members. In vitro analyses showed that one of these novel mutations together with two previously reported mutations (p.C913fs, p.R1036Q) significantly reduced the activity of the canonical Wnt signaling pathway. Such reductions may lead to decreased bone formation, and could explain the bone phenotype. Gut-derived Lrp5 has been shown to regulate serotonin synthesis by controlling the production of serotonin rate-limiting enzyme, Tph1. LRP5 mutations did not affect Tph1 expression, and only one mutant (p.L1149Q) reduced expression of serotonin receptor 5-Htr1b (p < 0.002). Conclusions Our results provide additional information on the role of LRP5 mutations and their effects on

  5. Reducing abnormal muscle co-activation after stroke using a myoelectric-computer interface: a pilot study

    PubMed Central

    Wright, Zachary A.; Zev Rymer, W.; Slutzky, Marc W.

    2014-01-01

    Background A significant factor in impaired movement caused by stroke is the inability to activate muscles independently. While the pathophysiology behind this abnormal co-activation is not clear, reducing the co-activation could improve overall arm function. A myoelectric computer interface (MCI), which maps EMG signals to cursor movement, could be used as a treatment to help retrain muscle activation patterns. Objective To investigate the use of MCI training to reduce abnormal muscle co-activation in chronic stroke survivors. Methods Five healthy subjects and five stroke survivors with hemiparesis participated in multiple sessions of MCI training. The level of arm impairment in stroke survivors was assessed using the upper extremity portion of Fugl-Meyer Motor Assessment (FMA-UE). Subjects performed isometric activations of up to five muscles. Activation of each muscle was mapped to different directions of cursor movement. The MCI specifically targeted one pair of muscles in each subject for reduction of co-activation. Results Both healthy subjects and stroke survivors learned to reduce abnormal co-activation of the targeted muscles with MCI training. Three out of five stroke survivors exhibited objective reduction in arm impairment as well (improvement in FMA-UE of 3 points in each of these subjects). Conclusions These results suggest that the MCI was an effective tool in directly retraining muscle activation patterns following stroke. PMID:24376069

  6. Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI.

    PubMed

    Frank, Sabine; Veit, Ralf; Sauer, Helene; Enck, Paul; Friederich, Hans-Christoph; Unholzer, Theresa; Bauer, Ute-Maria; Linder, Katarzyna; Heni, Martin; Fritsche, Andreas; Preissl, Hubert

    2016-05-01

    Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m(2) ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a 'wanting' and 'liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity. PMID:26450814

  7. T396I Mutation of Mouse Sufu Reduces the Stability and Activity of Gli3 Repressor

    PubMed Central

    Makino, Shigeru; Zhulyn, Olena; Mo, Rong; Puviindran, Vijitha; Zhang, Xiaoyun; Murata, Takuya; Fukumura, Ryutaro; Ishitsuka, Yuichi; Kotaki, Hayato; Matsumaru, Daisuke; Ishii, Shunsuke; Hui, Chi-Chung; Gondo, Yoichi

    2015-01-01

    Hedgehog signaling is primarily transduced by two transcription factors: Gli2, which mainly acts as a full-length activator, and Gli3, which tends to be proteolytically processed from a full-length form (Gli3FL) to an N-terminal repressor (Gli3REP). Recent studies using a Sufu knockout mouse have indicated that Sufu is involved in regulating Gli2 and Gli3 activator and repressor activity at multiple steps of the signaling cascade; however, the mechanism of specific Gli2 and Gli3 regulation remains to be elucidated. In this study, we established an allelic series of ENU-induced mouse strains. Analysis of one of the missense alleles, SufuT396I, showed that Thr396 residue of Sufu played a key role in regulation of Gli3 activity. SufuT396I/T396I embryos exhibited severe polydactyly, which is indicative of compromised Gli3 activity. Concomitantly, significant quantitative reductions of unprocessed Gli3 (Gli3FL) and processed Gli3 (Gli3REP) were observed in vivo as well as in vitro. Genetic experiments showed that patterning defects in the limb buds of SufuT396I/T396I were rescued by a constitutive Gli3REP allele (Gli3∆699), strongly suggesting that SufuT396I reduced the truncated Gli3 repressor. In contrast, SufuT396I qualitatively exhibited no mutational effects on Gli2 regulation. Taken together, the results of this study show that the Thr396 residue of Sufu is specifically required for regulation of Gli3 but not Gli2. This implies a novel Sufu-mediated mechanism in which Gli2 activator and Gli3 repressor are differentially regulated. PMID:25760946

  8. Breadth and Intensity: Salient, Separable, and Developmentally Significant Dimensions of Structured Youth Activity Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2009-01-01

    In recent years, an impressive volume of evidence has accumulated demonstrating that youth involvement in structured, organized activities (e.g. school sports, community clubs) may facilitate positive youth development. We present a theory-based framework for studying structured activity involvement (SAI) as a context for positive youth…

  9. Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa

    PubMed Central

    Gurunathan, Sangiliyandi; Han, Jae Woong; Dayem, Ahmed Abdal; Eppakayala, Vasuki; Kim, Jin-Hoi

    2012-01-01

    Background Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO) and reduced graphene oxide (rGO) in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME), for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared. Methods The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation. Results Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of cell viability, induced oxidative stress, and DNA fragmentation. Conclusion The antibacterial activities of GO and rGO against P. aeruginosa were compared. The loss of P

  10. Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles.

    PubMed

    Sun, Chuntang; Zhou, Le; Gou, Maling; Shi, Shuai; Li, Tao; Lang, Jinyi

    2016-06-01

    Doxorubicin (Dox) is a broad-spectrum antitumor drug used for the treatment of many types of malignant tumors. Although it possesses powerful antitumor activity, its clinical application is seriously encumbered by its unselective distribution and systemic toxicities, particularly myocardial toxicity. Thus, it is imperative to modify Dox to decrease its systemic toxicities and improve its therapeutic index. In the present study, we adopted a novel type of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles to encapsulate Dox to prepare Dox-loaded MPEG-PCL (Dox/MPEG-PCL) nanoparticles by a controllable self-assembly process. The cellular uptake efficiency and cell proliferation inhibition of the Dox/MPEG-PCL nanoparticles were examined. The antitumor activity of the Dox/MPEG-PCL nanoparticles was tested on a multiple pulmonary metastasis model of melanoma on C57BL/6 mice. Systemic toxicities and survival time were compared between the mice treated with the Dox/MPEG-PCL nanoparticles and free Dox. The potential myocardial toxicity of the Dox/MPEG-PCL nanoparticles was investigated using a prolonged observation period. Encapsulation of Dox in MPEG-PCL nanoparticles significantly improved the cellular uptake and cell proliferation inhibition of Dox in vivo. Intravenous injection of Dox/MPEG-PCL nanoparticles obtained significant inhibition of the growth and metastasis of melanoma in the lung and prolonged survival time compared with free Dox (P<0.05). The Dox/MPEG-PCL nanoparticles did not show obvious additional systemic toxicities compared with free Dox during the treatment time. During the prolonged observation period, obvious decreased cardiac toxicity was observed in the Dox/MPEG-PCL nanoparticle-treated mice compared with that observed in the free Dox-treated mice. These results indicated that encapsulating Dox with MPEG-PCL micelles could significantly promote its antitumor activity and reduce its toxicity to the myocardium. PMID

  11. Tensile properties of reduced activation Fe-9Cr-2W steels after FFTF irradiation

    NASA Astrophysics Data System (ADS)

    Kurishita, H.; Kayano, H.; Narui, M.; Kimura, A.; Hamilton, M. L.; Gelles, D. S.

    1994-09-01

    In order to develop radiation resistant steels with reduced activation for fusion reactor applications, the effect of fast neutron irradiation was investigated on the tensile properties of five types of Fe-9Cr-2W martensitic steel with and without small additions of boron, yttrium and aluminum. Miniature tensile specimens of the steels were irradiated to 28 dpa at 663 K and 33-35 dpa at 703, 793 and 873 K in the Fast Flux Test Facility (FFTF) and were deformed at temperatures between 300 and 873 K. The yield and ultimate tensile stresses were not significantly affected by the irradiations, but the total elongation was considerably decreased by the irradiation at 663 K. The reduction in elongation depended strongly on the test temperature with a maximum at around 673 K. The addition of yttrium alone tended to increase the high temperature strength, while the simultaneous addition of yttrium and aluminum tended to decrease the total elongation.

  12. Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy.

    PubMed

    Patel, C; Xu, Z; Shosha, E; Xing, J; Lucas, R; Caldwell, R W; Caldwell, R B; Narayanan, S P

    2016-09-01

    Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. New-born C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia. PMID:27239699

  13. Reduced nitrate leaching and enhanced denitrifier activity and efficiency in organically fertilized soils

    PubMed Central

    Kramer, Sasha B.; Reganold, John P.; Glover, Jerry D.; Bohannan, Brendan J. M.; Mooney, Harold A.

    2006-01-01

    Conventional agriculture has improved in crop yield but at large costs to the environment, particularly off-site pollution from mineral N fertilizers. In response to environmental concerns, organic agriculture has become an increasingly popular option. One component of organic agriculture that remains in question is whether it can reduce agricultural N losses to groundwater and the atmosphere relative to conventional agriculture. Here we report reduced N pollution from organic and integrated farming systems compared with a conventional farming system. We evaluated differences in denitrification potential and a suite of other soil biological and chemical properties in soil samples taken from organic, integrated, and conventional treatments in an experimental apple orchard. Organically farmed soils exhibited higher potential denitrification rates, greater denitrification efficiency, higher organic matter, and greater microbial activity than conventionally farmed soils. The observed differences in denitrifier function were then assessed under field conditions after fertilization. N2O emissions were not significantly different among treatments; however, N2 emissions were highest in organic plots. Annual nitrate leaching was 4.4–5.6 times higher in conventional plots than in organic plots, with the integrated plots in between. This study demonstrates that organic and integrated fertilization practices support more active and efficient denitrifier communities, shift the balance of N2 emissions and nitrate losses, and reduce environmentally damaging nitrate losses. Although this study specifically examines a perennial orchard system, the ecological and biogeochemical processes we evaluated are present in all agroecosystems, and the reductions in nitrate loss in this study could also be achievable in other cropping systems. PMID:16537377

  14. Reduced nitrate leaching and enhanced denitrifier activity and efficiency in organically fertilized soils.

    PubMed

    Kramer, Sasha B; Reganold, John P; Glover, Jerry D; Bohannan, Brendan J M; Mooney, Harold A

    2006-03-21

    Conventional agriculture has improved in crop yield but at large costs to the environment, particularly off-site pollution from mineral N fertilizers. In response to environmental concerns, organic agriculture has become an increasingly popular option. One component of organic agriculture that remains in question is whether it can reduce agricultural N losses to groundwater and the atmosphere relative to conventional agriculture. Here we report reduced N pollution from organic and integrated farming systems compared with a conventional farming system. We evaluated differences in denitrification potential and a suite of other soil biological and chemical properties in soil samples taken from organic, integrated, and conventional treatments in an experimental apple orchard. Organically farmed soils exhibited higher potential denitrification rates, greater denitrification efficiency, higher organic matter, and greater microbial activity than conventionally farmed soils. The observed differences in denitrifier function were then assessed under field conditions after fertilization. N(2)O emissions were not significantly different among treatments; however, N(2) emissions were highest in organic plots. Annual nitrate leaching was 4.4-5.6 times higher in conventional plots than in organic plots, with the integrated plots in between. This study demonstrates that organic and integrated fertilization practices support more active and efficient denitrifier communities, shift the balance of N(2) emissions and nitrate losses, and reduce environmentally damaging nitrate losses. Although this study specifically examines a perennial orchard system, the ecological and biogeochemical processes we evaluated are present in all agroecosystems, and the reductions in nitrate loss in this study could also be achievable in other cropping systems. PMID:16537377

  15. Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities.

    PubMed

    Beteck, Richard M; Coertzen, Dina; Smit, Frans J; Birkholtz, Lyn-Marie; Haynes, Richard K; N'Da, David D

    2016-07-01

    As part of a programme aimed at identifying rational new triple drug combinations for treatment of malaria, tuberculosis and toxoplasmosis, we have selected quinolones as one component, given that selected examples exhibit exceptionally good activities against the causative pathogens of the foregoing diseases. The quinolone decoquinate (DQ), an old and inexpensive coccidiostat, displays anti-malarial activity in vitro against Plasmodium falciparum (Pf). However, because of its exceedingly poor solubility in water or organic solvents, development of DQ as a drug is problematical. We have therefore converted DQ in straightforward fashion into tractable new derivatives that display good activities in vitro against chloroquine-sensitive NF54 and multidrug-resistant K1 and W2 Pf, and relatively low toxicities against human fibroblast cells. The most active compound, the N-acetyl derivative 30, is 5-fold more active than DQ against NF54 and K1 and equipotent with DQ against W2. It possesses an activity profile against all strains comparable with that of the artemisinin derivative artesunate. Overall, this compound and the other accessible and active derivatives serve as an attractive template for development of new and economic lead quinolones. PMID:27210430

  16. The Significance of Turning Passive Into Active in Control Mastery Theory

    PubMed Central

    FOREMAN, STEVEN A.

    1996-01-01

    Turning passive into active was first described by Freud but was later given expanded importance by Weiss. This new conceptualization of turning passive into active as an interpersonal communication and test has made a major contribution to the clinical treatment of difficult patients. This article reviews "control mastery" theory and puts its notion of passive-into-active testing into perspective with regard to Freud’s original conception as well as other conceptions, such as identification with the aggressor and projective identification. Formulation and the treatment of patients are illustrated with clinical examples. PMID:22700271

  17. Regular physical activity has differential association with reduced obesity among diverse youth in the United States.

    PubMed

    Fradkin, Chris; Wallander, Jan L; Elliott, Marc N; Cuccaro, Paula; Schuster, Mark A

    2016-08-01

    This study examined whether daily or almost daily lower-intensity physical activity was associated with reduced obesity, among 4824 African American, Hispanic, and White youth assessed in fifth and seventh grades. Regular lower-intensity physical activity was associated with reduced obesity only among Hispanic and White males and only in seventh grade, and not among youth in fifth grade, females, or African American males or females. Findings from this study suggest that the reduced obesity risk generally attributed to physical activity may not be consistent across racial/ethnic and gender groups of early adolescents. PMID:25476573

  18. Reduced Sensory Oscillatory Activity during Rapid Auditory Processing as a Correlate of Language-Learning Impairment

    PubMed Central

    Heim, Sabine; Friedman, Jennifer Thomas; Keil, Andreas; Benasich, April A.

    2010-01-01

    Successful language acquisition has been hypothesized to involve the ability to integrate rapidly presented, brief acoustic cues in sensory cortex. A body of work has suggested that this ability is compromised in language-learning impairment (LLI). The present research aimed to examine sensory integration during rapid auditory processing by means of electrophysiological measures of oscillatory brain activity using data from a larger longitudinal study. Twenty-nine children with LLI and control participants with typical language development (n=18) listened to tone doublets presented at a temporal interval that is essential for accurate speech processing (70-ms interstimulus interval). The children performed a deviant (pitch change of second tone) detection task, or listened passively. The electroencephalogram was recorded from 64 electrodes. Data were source-projected to the auditory cortices and submitted to wavelet analysis, resulting in time-frequency representations of electrocortical activity. Results show significantly reduced amplitude and phase-locking of early (45–75 ms) oscillations in the gamma-band range (29–52 Hz), specifically in the LLI group, for the second stimulus of the tone doublet. This suggests altered temporal organization of sensory oscillatory activity in LLI when processing rapid sequences. PMID:21822356

  19. Biological Significance of Local TGF-β Activation in Liver Diseases

    PubMed Central

    Hayashi, Hiromitsu; Sakai, Takao

    2012-01-01

    The cytokine transforming growth factor-β (TGF-β) plays a pivotal role in a diverse range of cellular responses, including cell proliferation, apoptosis, differentiation, migration, adhesion, angiogenesis, stimulation of extracellular matrix (ECM) synthesis, and downregulation of ECM degradation. TGF-β and its receptors are ubiquitously expressed by most cell types and tissues in vivo. In intact adult tissues and organs, TGF-β is secreted in a biologically inactive (latent) form associated in a non-covalent complex with the ECM. In response to injury, local latent TGF-β complexes are converted into active TGF-β according to a tissue- and injury type-specific activation mechanism. Such a well and tightly orchestrated regulation in TGF-β activity enables an immediate, highly localized response to type-specific tissue injury. In the pathological process of liver fibrosis, TGF-β plays as a master profibrogenic cytokine in promoting activation and myofibroblastic differentiation of hepatic stellate cells, a central event in liver fibrogenesis. Continuous and/or persistent TGF-β signaling induces sustained production of ECM components and of tissue inhibitor of metalloproteinase synthesis. Therefore, the regulation of locally activated TGF-β levels is increasingly recognized as a therapeutic target for liver fibrogenesis. This review summarizes our present knowledge of the activation mechanisms and bioavailability of latent TGF-β in biological and pathological processes in the liver. PMID:22363291

  20. Acquiring a Pet Dog Significantly Reduces Stress of Primary Carers for Children with Autism Spectrum Disorder: A Prospective Case Control Study.

    PubMed

    Wright, H F; Hall, S; Hames, A; Hardiman, J; Mills, R; Mills, D S

    2015-08-01

    This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3-10 weeks after acquisition) and follow-up (25-40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD. PMID:25832799

  1. Mutation in E1, the Ubiquitin Activating Enzyme, Reduces Drosophila Lifespan and Results in Motor Impairment

    PubMed Central

    Liu, Hsiu-Yu; Pfleger, Cathie M.

    2013-01-01

    Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease. PMID:23382794

  2. Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carrasco, D. I.

    2000-01-01

    The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.

  3. The Small Molecule Inhibitor G6 Significantly Reduces Bone Marrow Fibrosis and the Mutant Burden in a Mouse Model of Jak2-Mediated Myelofibrosis

    PubMed Central

    Kirabo, Annet; Park, Sung O.; Wamsley, Heather L.; Gali, Meghanath; Baskin, Rebekah; Reinhard, Mary K.; Zhao, Zhizhuang J.; Bisht, Kirpal S.; Keserű, György M.; Cogle, Christopher R.; Sayeski, Peter P.

    2013-01-01

    Philadelphia chromosome–negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocytosis, and myelofibrosis, are disorders characterized by abnormal hematopoiesis. Among these myeloproliferative neoplasms, myelofibrosis has the most unfavorable prognosis. Furthermore, currently available therapies for myelofibrosis have little to no efficacy in the bone marrow and hence, are palliative. We recently developed a Janus kinase 2 (Jak2) small molecule inhibitor called G6 and found that it exhibits marked efficacy in a xenograft model of Jak2-V617F–mediated hyperplasia and a transgenic mouse model of Jak2-V617F–mediated polycythemia vera/essential thrombocytosis. However, its efficacy in Jak2-mediated myelofibrosis has not previously been examined. Here, we hypothesized that G6 would be efficacious in Jak2-V617F–mediated myelofibrosis. To test this, mice expressing the human Jak2-V617F cDNA under the control of the vav promoter were administered G6 or vehicle control solution, and efficacy was determined by measuring parameters within the peripheral blood, liver, spleen, and bone marrow. We found that G6 significantly reduced extramedullary hematopoiesis in the liver and splenomegaly. In the bone marrow, G6 significantly reduced pathogenic Jak/STAT signaling by 53%, megakaryocytic hyperplasia by 70%, and the Jak2 mutant burden by 68%. Furthermore, G6 significantly improved the myeloid to erythroid ratio and significantly reversed the myelofibrosis. Collectively, these results indicate that G6 is efficacious in Jak2-V617F–mediated myelofibrosis, and given its bone marrow efficacy, it may alter the natural history of this disease. PMID:22796437

  4. Preliminary evidence of reduced brain network activation in patients with post-traumatic migraine following concussion.

    PubMed

    Kontos, Anthony P; Reches, Amit; Elbin, R J; Dickman, Dalia; Laufer, Ilan; Geva, Amir B; Shacham, Galit; DeWolf, Ryan; Collins, Michael W

    2016-06-01

    Post-traumatic migraine (PTM) (i.e., headache, nausea, light and/or noise sensitivity) is an emerging risk factor for prolonged recovery following concussion. Concussions and migraine share similar pathophysiology characterized by specific ionic imbalances in the brain. Given these similarities, patients with PTM following concussion may exhibit distinct electrophysiological patterns, although researchers have yet to examine the electrophysiological brain activation in patients with PTM following concussion. A novel approach that may help differentiate brain activation in patients with and without PTM is brain network activation (BNA) analysis. BNA involves an algorithmic analysis applied to multichannel EEG-ERP data that provides a network map of cortical activity and quantitative data during specific tasks. A prospective, repeated measures design was used to evaluate BNA (during Go/NoGo task), EEG-ERP, cognitive performance, and concussion related symptoms at 1, 2, 3, and 4 weeks post-injury intervals among athletes with a medically diagnosed concussion with PTM (n = 15) and without (NO-PTM) (n = 22); and age, sex, and concussion history matched controls without concussion (CONTROL) (n = 20). Participants with PTM had significantly reduced BNA compared to NO-PTM and CONTROLS for Go and NoGo components at 3 weeks and for NoGo component at 4 weeks post-injury. The PTM group also demonstrated a more prominent deviation of network activity compared to the other two groups over a longer period of time. The composite BNA algorithm may be a more sensitive measure of electrophysiological change in the brain that can augment established cognitive assessment tools for detecting impairment in individuals with PTM. PMID:26091725

  5. Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

    PubMed Central

    Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  6. Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity.

    PubMed

    Li, Ming; Yang, Yunjia; Yang, Yi; Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  7. Impurity content of reduced-activation ferritic steels and a vanadium alloy

    SciTech Connect

    Klueh, R.L.; Grossbeck, M.L.; Bloom, E.E.

    1997-04-01

    Inductively coupled plasma mass spectrometry was used to analyze a reduced-activation ferritic/martensitic steel and a vanadium alloy for low-level impurities that would compromise the reduced-activation characteristics of these materials. The ferritic steel was from the 5-ton IEA heat of modified F82H, and the vanadium alloy was from a 500-kg heat of V-4Cr-4Ti. To compare techniques for analysis of low concentrations of impurities, the vanadium alloy was also examined by glow discharge mass spectrometry. Two other reduced-activation steels and two commercial ferritic steels were also analyzed to determine the difference in the level of the detrimental impurities in the IEA heat and steels for which no extra effort was made to restrict some of the tramp impurities. Silver, cobalt, molybdenum, and niobium proved to be the tramp impurities of most importance. The levels observed in these two materials produced with present technology exceeded the limits for low activation for either shallow land burial or recycling. The chemical analyses provide a benchmark for the improvement in production technology required to achieve reduced activation; they also provide a set of concentrations for calculating decay characteristics for reduced-activation materials. The results indicate the progress that has been made and give an indication of what must still be done before the reduced-activation criteria can be achieved.

  8. Significant role of climatic trends on hydrothermal activity Coso Hot Springs, California

    SciTech Connect

    Lofgren, B.E. )

    1990-05-01

    The hydrothermal features of Coso Hot Springs have attracted visitors for 130 yr and scientific investigators for two decades. In 1978, anticipating effects of major geothermal developments nearby, the Naval Weapons Center (NWC) initiated a comprehensive monitoring program at a dozen hydrothermal sites in the Coso Hot Springs area. Nine years of monitoring preceded power production in the nearby Coso geothermal field in July 1987. During this period, steam was rising from numerous vents and gently boiling mud pots. Local rainfall caused increased boiling activity in several mud pots, with some overflowing during wet periods. Then in August 1988, a year after geothermal power production began major changes in hot spring activity commenced. Small mud pots and steamers started to grow and coalesce. In March 1989, mud-pot activity became more violent. Many buried wells failed causing surface activity in other areas to diminish. During ensuing months, large mud cones developed and much of the steam and boiling water occurred in a few major pots. Because the abrupt changes in hydrothermal activity followed so closely after nearby geothermal production began, the obvious cause has been attributed to geothermal developments. Studies of NWC baseline monitoring data indicate, however, that no effects of geothermal developments have been felt in the hot springs area. Rainfall and barometric effects account for most of the fluctuations in records of the past decade. Early accounts and field evidence suggest similar changes have occurred in the past.

  9. The evolution of magnetic activity on V711 Tauri and evidence for a significant facular contribution

    NASA Technical Reports Server (NTRS)

    Dorren, J. D.; Guinan, E. F.

    1990-01-01

    The nature of the long-term evolution of magnetic activity in the RS CVn binary V711 Tauri is investigated using the complete set of available archival IUE SWP low-dispersion spectra of V711 Tau for the period covering August 1978 - December 1984. An analysis of the spectra confirmed the pattern of a long-term smooth variation of chromospheric and transition region emission found previosly by Dorren et al. (1986). An explanation of the relationship between the different facets of the magnetic activity on V711 Tau is presented.

  10. Damping Control of Liquid Container by Swing-type Active Vibration Reducer on Mobile Robot

    NASA Astrophysics Data System (ADS)

    Hamaguchi, Masafumi; Taniguchi, Takao

    This paper proposes a damping control of sloshing in a cylindrical container with a swing-type active vibration reducer on a wheeled mobile robot (WMR). The WMR runs along a straight path on a horizontal plane. The container is mounted on the active vibration reducer. A laser displacement sensor is used to observe the liquid level in the container. The container can be tilted in the running direction by the active vibration reducer. A sloshing model is obtained from a spherical pendulum-type sloshing model, which approximately expresses (1, 1)-mode sloshing. The sloshing model is used to design a damping control system. The control system of the active vibration reducer is designed with an inverse model of sloshing and an optimal regulator with a Kalman filter. The WMR is driven by an acceleration pattern designed with an input shaping method. The usefulness of the proposed method is demonstrated through simulation and experimental results.

  11. Incresing antioxidant activity and reducing decay of blueberries by essential oils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several naturally occurring essential oils including carvacrol, anethole, cinnamaldehyde, cinnamic acid, perillaldehyde, linalool, and p-cymene were evaluated for their effectiveness in reducing decay and increasing antioxidant levels and activities in ‘Duke’ blueberries (Vaccinium corymbosum). Carv...

  12. The Social and Economic Significance of Recreation Activities in the Marine Environment.

    ERIC Educational Resources Information Center

    Ditton, Robert B.

    Although the data obtained by an Outdoor Recreation Resources Review Commission in 1960 indicated that 44 percent of participants in outdoor recreation prefer water-based activities, the potential demand for recreation within the coastal zone is much greater than that study indicates, because the unfulfilled recreational demands of the urban…

  13. The Measurement of Brain Electrical Activity and Its Significance to the Educator.

    ERIC Educational Resources Information Center

    Torello, Michael W.

    The article discusses the measurement of brain electrical activity and, in particular, the examination of electroencephalographic (EEG) data, as providing useful information in the diagnosis of dyslexia and other learning disabilities. Topographic imaging of EEG (TIE) is described as a procedure which provides functional data at comparatively low…

  14. Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

    NASA Technical Reports Server (NTRS)

    Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

    2000-01-01

    The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

  15. Reduced choice-related activity and correlated noise accompany perceptual deficits following unilateral vestibular lesion

    PubMed Central

    Liu, Sheng; Dickman, J. David; Newlands, Shawn D.; DeAngelis, Gregory C.; Angelaki, Dora E.

    2013-01-01

    Signals from the bilateral vestibular labyrinths work in tandem to generate robust estimates of our motion and orientation in the world. The relative contributions of each labyrinth to behavior, as well as how the brain recovers after unilateral peripheral damage, have been characterized for motor reflexes, but never for perceptual functions. Here we measure perceptual deficits in a heading discrimination task following surgical ablation of the neurosensory epithelium in one labyrinth. We found large increases in heading discrimination thresholds and large perceptual biases at 1 wk postlesion. Repeated testing thereafter improved heading perception, but vestibular discrimination thresholds remained elevated 3 mo postlesion. Electrophysiological recordings from the contralateral vestibular and cerebellar nuclei revealed elevated neuronal discrimination thresholds, elevated neurometric-to-psychometric threshold ratios, and reduced trial-by-trial correlations with perceptual decisions [“choice probabilities” (CPs)]. The relationship between CP and neuronal threshold was shallower, but not significantly altered, suggesting that smaller CPs in lesioned animals could be largely attributable to greater neuronal thresholds. Simultaneous recordings from pairs of neurons revealed that correlated noise among neurons was also reduced following the lesion. Simulations of a simple pooling model, which takes into account the observed changes in tuning slope and correlated noise, qualitatively accounts for the elevated psychophysical thresholds and neurometric-to-psychometric ratios, as well as the decreased CPs. Thus, cross-labyrinthine interactions appear to play important roles in enhancing neuronal and perceptual sensitivity, strengthening interneuronal correlations, and facilitating correlations between neural activity and perceptual decisions. PMID:24127575

  16. Facile synthesis of magnetically separable reduced graphene oxide/magnetite/silver nanocomposites with enhanced catalytic activity.

    PubMed

    Ji, Zhenyuan; Shen, Xiaoping; Yue, Xiaoyang; Zhou, Hu; Yang, Juan; Wang, Yuqin; Ma, Lianbo; Chen, Kangmin

    2015-12-01

    In this study, the combination of magnetite (Fe3O4) with reduced graphene oxide (RGO) generates a new hybrid substrate for the dispersion of noble metal nanoparticles. Well-dispersed silver (Ag) nanoparticles loaded on the surface of Fe3O4 modified RGO are achieved by an efficient two-step approach. Through reducing Ag(+) ions, highly dispersed Ag nanoparticles are in-situ formed on the RGO/Fe3O4 substrate. It is found that the existence of Fe3O4 nanocrystals can significantly improve the dispersity and decrease the particle size of the in-situ formed Ag nanoparticles. Magnetic study reveals that the as-prepared RGO/Fe3O4/Ag ternary nanocomposites display room-temperature superparamagnetic behavior. The catalytic properties of the RGO/Fe3O4/Ag ternary nanocomposites were evaluated with the reduction of 4-nitrophenol into 4-aminophenol as a model reaction. The as-synthesized RGO/Fe3O4/Ag ternary catalysts exhibit excellent catalytic stability and much higher catalytic activity than the corresponding RGO/Ag catalyst. Moreover, the RGO/Fe3O4/Ag catalysts can be easily magnetically separated for reuse. This study further demonstrates that nanoparticles modified graphene can act as an effective hybrid substrate for the synthesis of multi-component and multifunctional graphene-based composites. PMID:26263498

  17. Using the Significant Learning Taxonomy and Active Learning to Improve Accounting Education

    ERIC Educational Resources Information Center

    Killian, Larita J.; Brandon, Christopher D.

    2009-01-01

    Like other members of the academy, accounting professors are challenged to improve student learning. We must help students move beyond the "bean counter" role and develop higher-level skills such as analysis, synthesis, and problem-solving. The Significant Learning Taxonomy was used as a template to improve learning in an introductory accounting…

  18. Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients

    PubMed Central

    Lu, Linlin; Zhou, Juan; Shi, Jian; Peng, Xiao-juan; Qi, Xiao-xiao; Wang, Ying; Li, Fang-yuan; Zhou, Fu-Yuan; Liu, Liang; Liu, Zhong-Qiu

    2015-01-01

    UDP-glucuronosyltransferases (UGTs), the most important enzymes in body detoxification and homeostasis maintaining, govern the glucuronidation reaction of various endogenous and environmental carcinogens. The metabolic function of UGTs can be severely influenced by hepatocellular carcinoma (HCC), the fifth prevalent and third malignant cancer worldwide. Particularly in China, HBV-positive HCC account for approximately 80% of HCC patients. But rare papers addressed the alteration on the metabolism of UGTs specific substrates, translational and transcriptional activity of UGTs in HBV-positive HCC patients. In present study, we choose the main UGT isoforms, UGT1As, UGT1A1, UGT1A9, UGT1A4 and UGT2B7, to determine the alterations of metabolic activity, protein and gene expression of UGTs in HBV-positive HCC. The corresponding specific substrates such as genistein, SN-38, tamoxifen, propofol and zidovudine were utilized respectively in UGTs metabolic activity determination. Furthermore, the plausible mechanism responsible for UGTs alterations was addressed by analyzing the protein and gene expressions in tumor and the adjacent normal tissues in HBV-positive HCC. The results revealed that in the tumor human liver microsomes (HLMs), either Vmax (maximum reaction rate, Rmax for UGT1A1) or the clearance rates (Vmax/Km, Clint) of UGT1A, UGT1A1, UGT1A4, UGT1A9 and UGT2B7 were significant lower than those of in the adjacent normal HLMs. Subsequently, the relative protein and gene expressions of these isoforms were notably decreased in most of tumor tissues comparing with the adjacent normal tissues. More interestingly, in tumor tissues, the metabolic activity reduction ratio of each UGT isoform was closely related to its protein reduction ratio, indicating that decreasing protein level would contribute to the reduced metabolic function of UGTs in HBV-positive HCC. In summary, our study firstly determined the alteration of UGT function in HBV-positive HCC patients, which would

  19. Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients.

    PubMed

    Lu, Linlin; Zhou, Juan; Shi, Jian; Peng, Xiao-juan; Qi, Xiao-xiao; Wang, Ying; Li, Fang-Yuan; Zhou, Fu-Yuan; Liu, Liang; Liu, Zhong-Qiu

    2015-01-01

    UDP-glucuronosyltransferases (UGTs), the most important enzymes in body detoxification and homeostasis maintaining, govern the glucuronidation reaction of various endogenous and environmental carcinogens. The metabolic function of UGTs can be severely influenced by hepatocellular carcinoma (HCC), the fifth prevalent and third malignant cancer worldwide. Particularly in China, HBV-positive HCC account for approximately 80% of HCC patients. But rare papers addressed the alteration on the metabolism of UGTs specific substrates, translational and transcriptional activity of UGTs in HBV-positive HCC patients. In present study, we choose the main UGT isoforms, UGT1As, UGT1A1, UGT1A9, UGT1A4 and UGT2B7, to determine the alterations of metabolic activity, protein and gene expression of UGTs in HBV-positive HCC. The corresponding specific substrates such as genistein, SN-38, tamoxifen, propofol and zidovudine were utilized respectively in UGTs metabolic activity determination. Furthermore, the plausible mechanism responsible for UGTs alterations was addressed by analyzing the protein and gene expressions in tumor and the adjacent normal tissues in HBV-positive HCC. The results revealed that in the tumor human liver microsomes (HLMs), either V(max) (maximum reaction rate, R(max) for UGT1A1) or the clearance rates (V(max)/K(m), Clint) of UGT1A, UGT1A1, UGT1A4, UGT1A9 and UGT2B7 were significant lower than those of in the adjacent normal HLMs. Subsequently, the relative protein and gene expressions of these isoforms were notably decreased in most of tumor tissues comparing with the adjacent normal tissues. More interestingly, in tumor tissues, the metabolic activity reduction ratio of each UGT isoform was closely related to its protein reduction ratio, indicating that decreasing protein level would contribute to the reduced metabolic function of UGTs in HBV-positive HCC. In summary, our study firstly determined the alteration of UGT function in HBV-positive HCC patients, which

  20. Significantly enhancing supercapacitive performance of nitrogen-doped graphene nanosheet electrodes by phosphoric acid activation.

    PubMed

    Wang, Ping; He, Haili; Xu, Xiaolong; Jin, Yongdong

    2014-02-12

    In this work, we present a new method to synthesize the phosphorus, nitrogen contained graphene nanosheets, which uses dicyandiamide to prevent the aggregation of graphene oxide and act as the nitrogen precursor, and phosphoric acid (H3PO4) as the activation reagent. We have found that through the H3PO4 activation, the samples exhibit the remarkably enhanced supercapacitive performance, and depending on the amount of H3PO4 introduced, the specific capacitance of the samples is gradually increased from 7.6 to 244.6 F g(-1). Meanwhile, the samples also exhibit the good rate capability and excellent stability (up to 10 000 cycles). Through the transmission electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller analyses, H3PO4 treatment induced large pore volume and phosphorus related function groups in the product are assumed to response for the enhancement. PMID:24456232

  1. Primary School Children's Health-Enhancing Physical Activity Patterns: The School as a Significant Environment?

    ERIC Educational Resources Information Center

    Fairclough, S. J.; Butcher, Z. H.; Stratton, G.

    2008-01-01

    The moderate-to-vigorous physical activity (MVPA) of 70 children (age 8.6 years; 40 boys) was measured and gender and age differences were compared. Boys spent 28 minutes per day more than girls in MVPA (p=0.02, d=0.54), and younger children accumulated 24 minutes more MVPA than older peers (p=0.0001, d=0.91). Similar gender and age-related trends…

  2. Molecular and functional significance of Ca2+-activated Cl− channels in pulmonary arterial smooth muscle

    PubMed Central

    Forrest, Abigail S.; Ayon, Ramon J.; Wiwchar, Michael; Angermann, Jeff E.; Pritchard, Harry A. T.; Singer, Cherie A.; Valencik, Maria L.; Britton, Fiona; Greenwood, Iain A.

    2015-01-01

    Abstract Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca2+ levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K+ channels (e.g., Kv1.5) and increased expression and activity of voltage-dependent (Cav1.2) and voltage-independent (e.g., canonical and vanilloid transient receptor potential [TRPC and TRPV]) Ca2+ channels play an important role in the functional remodeling of pulmonary arteries in PH. This review focuses on an anion-permeable channel that is now considered a novel excitatory mechanism in the systemic and pulmonary circulations. It is permeable to Cl− and is activated by a rise in intracellular Ca2+ concentration (Ca2+-activated Cl− channel, or CaCC). The first section outlines the biophysical and pharmacological properties of the channel and ends with a description of the molecular candidate genes postulated to encode for CaCCs, with particular emphasis on the bestrophin and the newly discovered TMEM16 and anoctamin families of genes. The second section provides a review of the various sources of Ca2+ activating CaCCs, which include stimulation by mobilization from intracellular Ca2+ stores and Ca2+ entry through voltage-dependent and voltage-independent Ca2+ channels. The third and final section summarizes recent findings that suggest a potentially important role for CaCCs and the gene TMEM16A in PH. PMID:26064450

  3. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

    PubMed

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area. PMID:27366356

  4. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    PubMed Central

    Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed. PMID:27069488

  5. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review

    PubMed Central

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area. PMID:27366356

  6. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin.

    PubMed

    Li, Yuan; Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed. PMID:27069488

  7. Posterior parietal cortex activity reflects the significance of others' actions during natural viewing.

    PubMed

    Salmi, Juha; Glerean, Enrico; Jääskeläinen, Iiro P; Lahnakoski, Juha M; Kettunen, Juho; Lampinen, Jouko; Tikka, Pia; Sams, Mikko

    2014-09-01

    The posterior parietal cortex (PPC) has been associated with multiple stimulus-driven (e.g., processing stimulus movements, providing visual signals for the motor system), goal-directed (e.g., directing visual attention to a target, processing behavioral priority of intentions), and action-related functions in previous studies with non-naturalistic paradigms. Here, we examined how these functions reflect PPC activity during natural viewing. Fourteen healthy volunteers watched a re-edited movie during functional magnetic resonance imaging (fMRI). Participants separately annotated behavioral priority (accounting for percepts, thoughts, and emotions) they had experienced during movie episodes. Movements in the movie were quantified with computer vision and eye movements were recorded from a separate group of subjects. Our results show that while overlapping dorsomedial PPC areas respond to episodes with multiple types of stimulus content, ventrolateral PPC areas exhibit enhanced activity when viewing goal-directed human hand actions. Furthermore, PPC activity related to viewing goal-directed human hand actions was more accurately explained by behavioral priority than by movements of the stimulus or eye movements. Taken together, our results suggest that PPC participates in perception of goal-directed human hand actions, supporting the view that PPC has a special role in providing visual signals for the motor system ("how"), in addition to processing visual spatial movements ("where"). PMID:24706557

  8. Astragalus polysaccharide upregulates hepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase.

    PubMed

    Ren, Feng; Qian, Xin-Hua; Qian, Xin-Lai

    2016-03-25

    Thalassemia is a genetic disease characterized by iron overload which is a major detrimental factor contributing to mortality and organ damage. The hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. Lowering iron load in thalassemia patients by means of increasing hepcidin might be a therapeutic strategy. In this study, we first found that astragalus polysaccharide (APS) significantly increased hepcidin expression in HepG2 and L-02 cell lines originating from hepatocytes and mice liver, respectively. Following treatment with APS, the iron concentrations in serum, liver, spleen, and heart were significantly reduced in comparison to saline treated control mice. In further experiments, upregulation of interleukin-6 (IL-6) and enhanced p38 MAPK phosphorylation were detected in APS treated cells and mice, and as documented in previous studies, IL-6 and P38 MAPK phosphorylation are involved in the regulation of hepcidin expression. We also found that the effects of APS on upregulating hepcidin and IL-6 expressions could be antagonized by pretreatment with SB203580, an inhibitor of p38 MAPK signaling. These findings suggest that activation of p38 MAPK and release of IL-6 might mediate induction of hepcidin by APS. It is concluded that APS might have therapeutic implications in patients with iron overload, especially for thalassemia patients. PMID:26915800

  9. Moderate Weight Reduction in an Outpatient Obesity Intervention Program Significantly Reduces Insulin Resistance and Risk Factors for Cardiovascular Disease in Severely Obese Adolescents

    PubMed Central

    Grulich-Henn, J.; Lichtenstein, S.; Hörster, F.; Hoffmann, G. F.; Nawroth, P. P.; Hamann, A.

    2011-01-01

    Background. Metabolic risk factors like insulin resistance and dyslipidemia are frequently observed in severly obese children. We investigated the hypothesis that moderate weight reduction by a low-threshold intervention is already able to reduce insulin resistance and cardiovascular risk factors in severely obese children. Methods. A group of 58 severely obese children and adolescents between 8 and 17 years participating in a six-month-long outpatient program was studied before and after treatment. The program included behavioral treatment, dietary education and specific physical training. Metabolic parameters were measured in the fasting state, insulin resistance was evaluated in an oral glucose tolerance test. Results. Mean standard deviation score of the body mass index (SDS-BMI) in the study group dropped significantly from +2.5 ± 0.5 to 2.3 ± 0.6 (P < 0.0001) after participation in the program. A significant decrease was observed in HOMA (6.3 ± 4.2 versus 4.9 ± 2.4, P < 0.03, and in peak insulin levels (232.7 ± 132.4 versus 179.2 ± 73.3 μU/mL, P < 0.006). Significant reductions were also observed in mean levels of hemoglobin A1c, total cholesterol and LDL cholesterol. Conclusions. These data demonstrate that already moderate weight reduction is able to decrease insulin resistance and dyslipidemia in severely obese children and adolescents. PMID:21904547

  10. Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

    SciTech Connect

    Hoogsteen, Ilse J. . E-mail: i.hoogsteen@rther.umcn.nl; Pop, Lucas A.M.; Marres, Henri A.M.; Hoogen, Franciscus J.A. van den; Kaanders, Johannes H.A.M.

    2006-01-01

    Purpose: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). Methods and Materials: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. Results: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seen among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). Conclusion: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.

  11. Brief psychosocial-behavioral intervention with antidepressant reduces post-stroke depression significantly more than usual care with antidepressant: Living Well with Stroke randomized controlled trial

    PubMed Central

    Mitchell, Pamela H.; Veith, Richard C.; Becker, Kyra J.; Buzaitis, Ann; Cain, Kevin C.; Fruin, Michael; Tirschwell, David; Teri, Linda

    2009-01-01

    Background and Purpose Depression following stroke is prevalent, diminishing recovery and quality of life. Brief behavioral intervention, adjunctive to antidepressant therapy has not been well evaluated for long-term efficacy in those with post-stroke depression. Methods 101 clinically depressed ischemic stroke patients within four months of index stroke were randomly assigned to an 8 week brief psychosocial-behavioral intervention plus antidepressant or usual care, including antidepressant. Primary endpoint was reduction in depressive symptom severity at 12 months following entry. Results Hamilton Rating Scale for Depression (HRSD) raw score in the intervention group was significantly lower immediately post-treatment (p = < 0.001) and at 12 months (p = 0.05) compared to controls. Remission (HRSD < 10), was significantly greater immediately post-treatment and at 12 months in the intervention group compared to usual care control. The mean percent decrease (47% ± 26% intervention versus 32% ± 36% control, p = .02) and the mean absolute decrease (-9.2 ± 5.7 intervention versus -6.2 ± 6.4 control, p = 0.023) in HRSD at 12 months were clinically important and statistically significant in the intervention group compared to control. Conclusion A brief psychosocial/behavioral intervention is highly effective in reducing depression in both the short and long term. PMID:19661478

  12. Reduced Maximal Force during Acute Anterior Knee Pain Is Associated with Deficits in Voluntary Muscle Activation

    PubMed Central

    Salomoni, Sauro; Tucker, Kylie; Hug, François; McPhee, Megan; Hodges, Paul

    2016-01-01

    Although maximal voluntary contraction (MVC) force is reduced during pain, studies using interpolated twitch show no consistent reduction of voluntary muscle drive. The present study aimed to test if the reduction in MVC force during acute experimental pain could be explained by increased activation of antagonist muscles, weak voluntary activation at baseline, or changes in force direction. Twenty-two healthy volunteers performed maximal voluntary isometric knee extensions before, during, and after the effects of hypertonic (pain) and isotonic (control) saline injections into the infrapatellar fat pad. The MVC force, voluntary activation, electromyographic (EMG) activity of agonist, antagonist, and auxiliary (hip) muscles, and pain cognition and anxiety scores were recorded. MVC force was 9.3% lower during pain than baseline (p < 0.001), but there was no systematic change in voluntary activation. Reduced MVC force during pain was variable between participants (SD: 14%), and was correlated with reduced voluntary activation (r = 0.90), baseline voluntary activation (r = − 0.62), and reduced EMG amplitude of agonist and antagonist muscles (all r > 0.52), but not with changes in force direction, pain or anxiety scores. Hence, reduced MVC force during acute pain was mainly explained by deficits in maximal voluntary drive. PMID:27559737

  13. Denervation-Induced Activation of the Ubiquitin-Proteasome System Reduces Skeletal Muscle Quantity Not Quality.

    PubMed

    Baumann, Cory W; Liu, Haiming M; Thompson, LaDora V

    2016-01-01

    It is well known that the ubiquitin-proteasome system is activated in response to skeletal muscle wasting and functions to degrade contractile proteins. The loss of these proteins inevitably reduces skeletal muscle size (i.e., quantity). However, it is currently unknown whether activation of this pathway also affects function by impairing the muscle's intrinsic ability to produce force (i.e., quality). Therefore, the purpose of this study was twofold, (1) document how the ubiquitin-proteasome system responds to denervation and (2) identify the physiological consequences of these changes. To induce soleus muscle atrophy, C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14 days (n = 6-8 per group). At these time points, content of several proteins within the ubiquitin-proteasome system were determined via Western blot, while ex vivo whole muscle contractility was specifically analyzed at day 14. Denervation temporarily increased several key proteins within the ubiquitin-proteasome system, including the E3 ligase MuRF1 and the proteasome subunits 19S, α7 and β5. These changes were accompanied by reductions in absolute peak force and power, which were offset when expressed relative to physiological cross-sectional area. Contrary to peak force, absolute and relative forces at submaximal stimulation frequencies were significantly greater following 14 days of denervation. Taken together, these data represent two keys findings. First, activation of the ubiquitin-proteasome system is associated with reductions in skeletal muscle quantity rather than quality. Second, shortly after denervation, it appears the muscle remodels to compensate for the loss of neural activity via changes in Ca2+ handling. PMID:27513942

  14. IgG immunoadsorption reduces systemic lupus erythematosus activity and proteinuria: a long term observational study

    PubMed Central

    Stummvoll, G; Aringer, M; Smolen, J; Schmaldienst, S; Jimenez-Boj, E; Horl, W; Graninger, W; Derfler, K

    2005-01-01

    Objective: To analyse the effects of rigorous immunoglobulin removal by immunoadsorption (IAS) on proteinuria (primary outcome variable), disease activity (SIS, SLEDAI, ECLAM), and autoantibodies to double stranded DNA (anti-dsDNA) in active systemic lupus erythematosus (SLE). Methods: 16 patients with severe SLE and renal disease, in whom cyclophosphamide was contraindicated or failed to halt disease progression, were treated with IAS for 3 months. Patients achieving at least 20% improvement in two or more of the outcome measures were considered responders and offered a 9 months' extension period. Results: Within 3 months, 14 patients responded and 11 opted for an extension. Proteinuria decreased from 6.7 (4.6) g/day (mean (SD)) at baseline to 4.3 (3.5) g/day at 3 months and 2.9 (2.4) g/day at 12 months (p<0.001). From baseline to 3 and 12 months, disease activity improved independently of scoring by SIS (15 (5) to 5 (2) and to 5 (2), p<0.0001), SLEDAI (21 (7) to 5 (4) and to 5 (4), p<0.0001), or ECLAM (7 (2) to 2 (1) and to 3 (1), p<0.0001). Anti-dsDNA fell from 391 (647) IU/ml to 146 (218) and to 53 (50) IU/ml at 3 and 12 months, respectively. Steroids could be tapered from 117 (159) mg/day at baseline to 29 (17) mg/day at 3 months and 9 (2) mg/day at 12 months. IAS was not associated with an excess of infections. However, one patient died of septicaemia after 1 month of treatment. Conclusion: In this negatively selected cohort of patients with SLE, IAS was associated with a significant response shown by reduced proteinuria, improved global disease activity, decreased anti-dsDNA, and lower glucocorticoid dosages, suggesting therapeutic benefit. PMID:15640267

  15. Denervation-Induced Activation of the Ubiquitin-Proteasome System Reduces Skeletal Muscle Quantity Not Quality

    PubMed Central

    Liu, Haiming M.; Thompson, LaDora V.

    2016-01-01

    It is well known that the ubiquitin-proteasome system is activated in response to skeletal muscle wasting and functions to degrade contractile proteins. The loss of these proteins inevitably reduces skeletal muscle size (i.e., quantity). However, it is currently unknown whether activation of this pathway also affects function by impairing the muscle’s intrinsic ability to produce force (i.e., quality). Therefore, the purpose of this study was twofold, (1) document how the ubiquitin-proteasome system responds to denervation and (2) identify the physiological consequences of these changes. To induce soleus muscle atrophy, C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14 days (n = 6–8 per group). At these time points, content of several proteins within the ubiquitin-proteasome system were determined via Western blot, while ex vivo whole muscle contractility was specifically analyzed at day 14. Denervation temporarily increased several key proteins within the ubiquitin-proteasome system, including the E3 ligase MuRF1 and the proteasome subunits 19S, α7 and β5. These changes were accompanied by reductions in absolute peak force and power, which were offset when expressed relative to physiological cross-sectional area. Contrary to peak force, absolute and relative forces at submaximal stimulation frequencies were significantly greater following 14 days of denervation. Taken together, these data represent two keys findings. First, activation of the ubiquitin-proteasome system is associated with reductions in skeletal muscle quantity rather than quality. Second, shortly after denervation, it appears the muscle remodels to compensate for the loss of neural activity via changes in Ca2+ handling. PMID:27513942

  16. Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats

    PubMed Central

    Cissé, Youssouf; Inoue, Isao; Kido, Hiroshi

    2012-01-01

    Background Oseltamivir phosphate (OP, Tamiflu®) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. Objective The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. Methods Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 105 plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. Results We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. Conclusion Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.

  17. Epicatechin Reduces Striatal MPP⁺-Induced Damage in Rats through Slight Increases in SOD-Cu,Zn Activity.

    PubMed

    Rubio-Osornio, M; Gorostieta-Salas, E; Montes, S; Pérez-Severiano, F; Rubio, C; Gómez, C; Ríos, C; Guevara, J

    2015-01-01

    Parkinson's disease is a neurodegenerative disorder characterized by movement alterations caused by reduced dopaminergic neurotransmission in the nigrostriatal pathway, presumably by oxidative stress (OS). MPP(+) intrastriatal injection leads to the overproduction of free radicals (FR). The increasing formation of FR produces OS, a decline in dopamine (DA) content, and behavioral disorders. Epicatechin (EC) has shown the ability to be FR scavenger, an antioxidant enzyme inductor, a redox state modulator, and transition metal chelator. Acute administration of 100 mg/kg of EC significantly prevented (P < 0.05) the circling MPP(+)-induced behavior (10 μg/8 μL). Likewise, EC significantly (P < 0.05) reduced the formation of fluorescent lipid products caused by MPP(+). MPP(+) injection produced (P < 0.05) increased enzymatic activity of the constitutive nitric oxide synthase (cNOS). This effect was blocked with acute EC pretreatment. Cu/Zn-dependent superoxide dismutase (Cu/Zn-SOD) activity was significantly (P < 0.05) reduced as a consequence of MPP(+) damage. EC produced a slight increase (≈20%) in Cu/Zn-SOD activity in the control group. Such effects persisted in animals injured with MPP(+). The results show that EC is effective against MPP(+)-induced biochemical and behavioral damage, which is possible by an increase in Cu/Zn-SOD activity. PMID:26301040

  18. Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment

    PubMed Central

    Kurien, Biji T; Harris, Valerie M; Quadri, Syed M S; Coutinho-de Souza, Patricia; Cavett, Joshua; Moyer, Amanda; Ittiq, Bilal; Metcalf, Angela; Ramji, Husayn F; Truong, Dat; Kumar, Ramesh; Koelsch, Kristi A; Centola, Mike; Payne, Adam; Danda, Debashish; Scofield, R Hal

    2015-01-01

    Objectives Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)). We hypothesised that UsC or ultrasoluble turmeric (UsT) will ameliorate systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS)-like disease in MRL-lpr/lpr mice. Methods Eighteen female MRL-lpr/lpr (6 weeks old) and 18 female MRL-MpJ mice (6 weeks old) were used. Female MRL-lpr/lpr mice develop lupus-like disease at the 10th week and die at an average age of 17 weeks. MRL-MpJ mice develop lupus-like disease around 47 weeks and typically die at 73 weeks. Six mice of each strain received autoclaved water only (lpr-water or MpJ-water group), UsC (lpr-CU or MpJ-CU group) or UsT (lpr-TU or MpJ-TU group) in the water bottle. Results UsC or UsT ameliorates SLE in the MRL-lpr/lpr mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. lpr-CU group had a 20% survival advantage over lpr-water group. However, lpr-TU group lived an average of 16 days shorter than lpr-water group due to complications unrelated to lupus-like illness. CU/TU treatment inhibited lymphadenopathy significantly compared with lpr-water group (p=0.03 and p=0.02, respectively) by induction of apoptosis. Average lymph node weights were 2606±1147, 742±331 and 385±68 mg, respectively, for lpr-water, lpr-CU and lpr-TU mice. Transferase dUTP nick end labelling assay showed that lymphocytes in lymph nodes of lpr-CU and lpr-TU mice underwent apoptosis. Significantly reduced cellular infiltration of the salivary glands in the lpr-TU group compared with the lpr-water group, and a trend towards reduced kidney damage was observed in

  19. Reducing Dilution and Analysis Time in Online Comprehensive Two-Dimensional Liquid Chromatography by Active Modulation.

    PubMed

    Gargano, Andrea F G; Duffin, Mike; Navarro, Pablo; Schoenmakers, Peter J

    2016-02-01

    Online comprehensive two-dimensional liquid chromatography (LC × LC) offers ways to achieve high-performance separations in terms of peak capacity (exceeding 1000) and additional selectivity to realize applications that cannot be addressed with one-dimensional chromatography (1D-LC). However, the greater resolving power of LC × LC comes at the price of higher dilutions (thus, reduced sensitivity) and, often, long analysis times (>100 min). The need to preserve the separation attained in the first dimension ((1)D) causes greater dilution for LC × LC, in comparison with 1D-LC, and long analysis times to sample the (1)D with an adequate number of second dimension separations. A way to significantly reduce these downsides is to introduce a concentration step between the two chromatographic dimensions. In this work we present a possible active-modulation approach to concentrate the fractions of (1)D effluent. A typical LC × LC system is used with the addition of a dilution flow to decrease the strength of the (1)D effluent and a modulation unit that uses trap columns. The potential of this approach is demonstrated for the separation of tristyrylphenol ethoxylate phosphate surfactants, using a combination of hydrophilic interaction and reversed-phase liquid chromatography. The modified LC × LC system enabled us to halve the analysis time necessary to obtain a similar degree of separation efficiency with respect to UHPLC based LC × LC and of 5 times with respect to HPLC instrumentation (40 compared with 80 and 200 min, respectively), while at the same time reducing dilution (DF of 142, 299, and 1529, respectively) and solvent consumption per analysis (78, 120, and 800 mL, respectively). PMID:26709410

  20. Smoke exposure of human macrophages reduces HDAC3 activity, resulting in enhanced inflammatory cytokine production.

    PubMed

    Winkler, Aaron R; Nocka, Karl N; Williams, Cara M M

    2012-08-01

    Chronic obstructive pulmonary disease (COPD) is a debilitating condition resulting from exposure to pollutants such as cigarette smoke. Pulmonary macrophages secrete a plethora of inflammatory mediators that are increased in the lungs of COPD patients, but whether this phenotype results directly from smoke exposure remains unknown. Using an in vitro model for alveolar macrophages (AM) derived from human peripheral blood monocytes with granulocyte-macrophage stimulating factor (GM-MØ), we analyzed the mechanistic connection between cigarette smoke exposure and histone deacetylase (HDAC) regulation, hypothesized to be a contributing factor in COPD pathophysiology. Here we show that acute smoke exposure inhibits HDAC enzymatic activity in GM-MØ. Analysis of mRNA and total cellular proteins for expression of class I (1, 2, 3 and 8), class II (4, 5, 6, 7, 9, 10), and class IV (11) HDAC revealed no effect of smoke exposure, whereas nuclear HDAC3 protein content was reduced. To better understand the physiological significance of reduced HDAC3 activity, we utilized siRNA to knockdown HDAC1, 2 and 3 individually. Interestingly, siRNA-mediated reduction of HDAC3 resulted in increased production of IL8 and IL1β in response to LPS stimulation, while HDAC2 knockdown had no effect on either cytokine. Lower nuclear content of HDAC3 in the context of equivalent total HDAC protein levels following smoke exposure may reflect increased nuclear export of HDAC3, allowing increased nuclear factor kappa b (NF-κB ) driven cytokine expression that can contribute to inflammation. PMID:22613758

  1. Hypoxia Reduces Arylsulfatase B Activity and Silencing Arylsulfatase B Replicates and Mediates the Effects of Hypoxia

    PubMed Central

    Bhattacharyya, Sumit; Tobacman, Joanne K.

    2012-01-01

    This report presents evidence of 1) a role for arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) in mediating intracellular oxygen signaling; 2) replication between the effects of ARSB silencing and hypoxia on sulfated glycosaminoglycan content, cellular redox status, and expression of hypoxia-associated genes; and 3) a mechanism whereby changes in chondroitin-4-sulfation that follow either hypoxia or ARSB silencing can induce transcriptional changes through galectin-3. ARSB removes 4-sulfate groups from the non-reducing end of chondroitin-4-sulfate and dermatan sulfate and is required for their degradation. For activity, ARSB requires modification of a critical cysteine residue by the formylglycine generating enzyme and by molecular oxygen. When primary human bronchial and human colonic epithelial cells were exposed to 10% O2×1 h, ARSB activity declined by ∼41% and ∼30% from baseline, as nuclear hypoxia inducible factor (HIF)-1α increased by ∼53% and ∼37%. When ARSB was silenced, nuclear HIF-1α increased by ∼81% and ∼61% from baseline, and mRNA expression increased to 3.73 (±0.34) times baseline. Inversely, ARSB overexpression reduced nuclear HIF-1α by ∼37% and ∼54% from baseline in the epithelial cells. Hypoxia, like ARSB silencing, significantly increased the total cellular sulfated glycosaminoglycans and chondroitin-4-sulfate (C4S) content. Both hypoxia and ARSB silencing had similar effects on the cellular redox status and on mRNA expression of hypoxia-associated genes. Transcriptional effects of both ARSB silencing and hypoxia may be mediated by reduction in galectin-3 binding to more highly sulfated C4S, since the galectin-3 that co-immunoprecipitated with C4S declined and the nuclear galectin-3 increased following ARSB knockdown and hypoxia. PMID:22428001

  2. Effect of viscous macromolecules on peritoneal plasminogen activator activity: a potential mechanism for their ability to reduce postoperative adhesion formation.

    PubMed

    Mayer, M; Yedgar, S; Hurwitz, A; Palti, Z; Finzi, Z; Milwidsky, A

    1988-10-01

    Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces. PMID:2459968

  3. Insecticidal Activity of Some Reducing Sugars Against the Sweet Potato Whitefly, Bemisia tabaci, Biotype B

    PubMed Central

    Hu, Jing S.; Gelman, Dale B.; Salvucci, Michael E.; Chen, Yan P.; Blackburn, Michael B.

    2010-01-01

    The effects of 16 sugars (arabinose, cellobiose, fructose, galactose, gentiobiose, glucose, inositol, lactose, maltose, mannitol (a sugar alcohol), mannose, melibiose, ribose, sorbitol, trehalose, and xylose) on sweet potato whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) survival were determined using in vitro bioassays. Of these sugars, arabinose, mannose, ribose, and xylose were strongly inhibitory to both nymphal and adult survival. When 10% mannose was added to the nymphal diet, 10.5%, 1.0%, and 0% developed to the 2nd, 3rd, and 4th instars, respectively. When 10% arabinose was added, 10.8% and 0% of the nymphs molted to the 2nd and 3rd instars, respectively. Addition of 10% xylose or ribose completely terminated B. tabaci development, preventing the molt to the 2nd instar. With decreasing sugar concentrations the inhibitory effect was significantly reduced. In tests using adults, arabinose, galactose, inositol, lactose, maltose, mannitol, mannose, melibiose, ribose, sorbitol, trehalose, and xylose significantly reduced mean day survival. Mortality rates were highest when arabinose, mannitol, mannose, ribose, or xylose was added to the diet. Mean day survival was less than 2 days when adults were fed on diet containing 10% of any one of these five sugars. When lower concentrations of sugars were used there was a decrease in mortality. Mode of action studies revealed that toxicity was not due to the inhibition of alpha glucosidase (converts sucrose to glucose and fructose) and/or trehalulose synthase (converts sucrose to trehalulose) activity. The result of agarose gel electrophoresis of RT-PCR products of bacterial endosymbionts amplified from RNA isolated from whiteflies fed with 10% arabinose, mannose, or xylose indicated that the concentration of endosymbionts in mycetomes was not affected by the toxic sugars. Experiments in which B. tabaci were fed on diets that contained radio-labeled sucrose, methionine or inulin and one or none (control) of

  4. Dissociated functional significance of decision-related activity in the primate dorsal stream.

    PubMed

    Katz, Leor N; Yates, Jacob L; Pillow, Jonathan W; Huk, Alexander C

    2016-07-14

    During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making, with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding. The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions. PMID:27376476

  5. UNESCO active learning approach in optics and photonics leads to significant change in Morocco

    NASA Astrophysics Data System (ADS)

    Berrada, K.; Channa, R.; Outzourhit, A.; Azizan, M.; Oueriagli, A.

    2014-07-01

    There are many difficulties in teaching science and technology in developing countries. Several different teaching strategies have to be applied in these cases. More specifically, for developing countries competencies in teaching science in the introductory classroom has attracted much attention. As a specific example we will consider the Moroccan system. In most developing countries everything is moving so slowly that the progress stays static for development. Also, any change needs time, effort and engagement. In our case we discovered that many teachers feel uncomfortable when introducing new teaching methods and evaluation in classes at introductory physics. However, the introduction of an Active Learning in our curricula showed difficulties that students have in understanding physics and especially concepts. Students were interested in having Active Learning courses much more than passive and traditional ones. Changing believes on physical phenomena and reality of the world students become more attractive and their way of thinking Science changed. The main philosophy of fostering modern hands-on learning techniques -adapted to local needs and availability of teaching resources- is elaborated. The Active Learning program provides the teachers with a conceptual evaluation instrument, drawn from relevant physics education research, giving teachers an important tool to measure student learning. We will try to describe the UNESCO Chair project in physics created in 2010 at Cadi Ayyad University since our first experience with UNESCO ALOP program. Many efforts have been done so far and the project helps now to develop more national and international collaborations between universities and Regional Academies of Education and Training. As a new result of these actions and according to our local needs, the translation of the ALOP program into Arabic is now available under the auspice of UNESCO and encouragement of international partners SPIE, ICTP, ICO and OSA.

  6. Combined steam and ultrasound treatment of broilers at slaughter: a promising intervention to significantly reduce numbers of naturally occurring campylobacters on carcasses.

    PubMed

    Musavian, Hanieh S; Krebs, Niels H; Nonboe, Ulf; Corry, Janet E L; Purnell, Graham

    2014-04-17

    Steam or hot water decontamination treatment of broiler carcasses is hampered by process limitations due to prolonged treatment times and adverse changes to the epidermis. In this study, a combination of steam with ultrasound (SonoSteam®) was investigated on naturally contaminated broilers that were processed at conventional slaughter speeds of 8,500 birds per hour in a Danish broiler plant. Industrial-scale SonoSteam equipment was installed in the evisceration room, before the inside/outside carcass washer. The SonoSteam treatment was evaluated in two separate trials performed on two different dates. Numbers of naturally occurring Campylobacter spp. and TVC were determined from paired samples of skin excised from opposite sides of the breast of the same carcass, before and after treatments. Sampling was performed at two different points on the line: i) before and after the SonoSteam treatment and ii) before the SonoSteam treatment and after 80 min of air chilling. A total of 44 carcasses were examined in the two trials. Results from the first trial showed that the mean initial Campylobacter contamination level of 2.35 log₁₀ CFU was significantly reduced (n=12, p<0.001) to 1.40 log₁₀ CFU after treatment. A significant reduction (n=11, p<0.001) was also observed with samples analyzed before SonoSteam treatment (2.64 log₁₀ CFU) and after air chilling (1.44 log₁₀ CFU). In the second trial, significant reductions (n=10, p<0.05) were obtained for carcasses analyzed before (mean level of 2.23 log₁₀ CFU) and after the treatment (mean level of 1.36 log₁₀ CFU). Significant reductions (n=11, p<0.01) were also found for Campylobacter numbers analyzed before the SonoSteam treatment (2.02 log₁₀ CFU) and after the air chilling treatment (1.37 log₁₀ CFU). The effect of air chilling without SonoSteam treatment was determined using 12 carcasses pre- and postchill. Results showed insignificant reductions of 0.09 log₁₀ from a mean initial level of

  7. Tissue Plasminogen Activator Coating on Implant Surfaces Reduces Staphylococcus aureus Biofilm Formation

    PubMed Central

    Na, Manli; Jarneborn, Anders; Jacobsson, Gunnar; Peetermans, Marijke; Verhamme, Peter

    2015-01-01

    Staphylococcus aureus biofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role in S. aureus biofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating on S. aureus biofilm formation was tested with in vitro microplate biofilm assays and an in vivo mouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by various S. aureus strains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics. In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduce S. aureus biofilm formation both in vitro and in vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices. PMID:26519394

  8. Aryl Hydrocarbon Receptor Activation by TCDD Reduces Inflammation Associated with Crohn's Disease

    PubMed Central

    Benson, Jenna M.; Shepherd, David M.

    2011-01-01

    Crohn's disease results from a combination of genetic and environmental factors that trigger an inappropriate immune response to commensal gut bacteria. The aryl hydrocarbon receptor (AhR) is well known for its involvement in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant that affects people primarily through the diet. Recently, TCDD was shown to suppress immune responses by generating regulatory T cells (Tregs). We hypothesized that AhR activation dampens inflammation associated with Crohn's disease. To test this hypothesis, we utilized the 2,4,6-trinitrobenzenesulfonic acid (TNBS) murine model of colitis. Mice were gavaged with TCDD prior to colitis induction with TNBS. Several parameters were examined including colonic inflammation via histological and flow cytometric analyses. TCDD-treated mice recovered body weight faster and experienced significantly less colonic damage. Reduced levels of interleukin (IL) 6, IL-12, interferon-gamma, and tumor necrosis factor-α demonstrated suppression of inflammation in the gut following TCDD exposure. Forkhead box P3 (Foxp3)egfp mice revealed that TCDD increased the Foxp3+ Treg population in gut immune tissue following TNBS exposure. Collectively, these results suggest that activation of the AhR by TCDD decreases colonic inflammation in a murine model of colitis in part by generating regulatory immune cells. Ultimately, this work may lead to the development of more effective therapeutics for the treatment of Crohn's disease. PMID:21131560

  9. Allopurinol reduces antigen-specific and polyclonal activation of human T cells

    PubMed Central

    Pérez-Mazliah, Damián; Albareda, María C.; Alvarez, María G.; Lococo, Bruno; Bertocchi, Graciela L.; Petti, Marcos; Viotti, Rodolfo J.; Laucella, Susana A.

    2012-01-01

    Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza (Flu) virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases. PMID:23049532

  10. Development of new generation reduced activation ferritic-martensitic steels for advanced fusion reactors

    NASA Astrophysics Data System (ADS)

    Tan, L.; Snead, L. L.; Katoh, Y.

    2016-09-01

    International development of reduced activation ferritic-martensitic (RAFM) steels has focused on 9 wt percentage Cr, which primarily contain M23C6 (M = Cr-rich) and small amounts of MX (M = Ta/V, X = C/N) precipitates, not adequate to maintain strength and creep resistance above ∼500 °C. To enable applications at higher temperatures for better thermal efficiency of fusion reactors, computational alloy thermodynamics coupled with strength modeling have been employed to explore a new generation RAFM steels. The new alloys are designed to significantly increase the amount of MX nanoprecipitates, which are manufacturable through standard and scalable industrial steelmaking methods. Preliminary experimental results of the developed new alloys demonstrated noticeably increased amount of MX, favoring significantly improved strength, creep resistance, and Charpy impact toughness as compared to current RAFM steels. The strength and creep resistance were comparable or approaching to the lower bound of, but impact toughness was noticeably superior to 9-20Cr oxide dispersion-strengthened ferritic alloys.

  11. Development of new generation reduced activation ferritic-martenstic steels for advanced fusion reactors

    DOE PAGESBeta

    Tan, Lizhen; Snead, Lance Lewis; Katoh, Yutai

    2016-05-26

    International development of reduced activation ferritic-martensitic (RAFM) steels has focused on 9 wt percentage Cr, which primarily contain M23C6 (M = Cr-rich) and small amounts of MX (M = Ta/V, X = C/N) precipitates, not adequate to maintain strength and creep resistance above ~500 °C. To enable applications at higher temperatures for better thermal efficiency of fusion reactors, computational alloy thermodynamics coupled with strength modeling have been employed to explore a new generation RAFM steels. The new alloys are designed to significantly increase the amount of MX nanoprecipitates, which are manufacturable through standard and scalable industrial steelmaking methods. Preliminary experimentalmore » results of the developed new alloys demonstrated noticeably increased amount of MX, favoring significantly improved strength, creep resistance, and Charpy impact toughness as compared to current RAFM steels. Furthermore, the strength and creep resistance were comparable or approaching to the lower bound of, but impact toughness was noticeably superior to 9–20Cr oxide dispersion-strengthened ferritic alloys.« less

  12. Reduced heat pain thresholds after sad-mood induction are associated with changes in thalamic activity.

    PubMed

    Wagner, Gerd; Koschke, Mandy; Leuf, Tanja; Schlösser, Ralf; Bär, Karl-Jürgen

    2009-03-01

    Negative affective states influence pain processing in healthy subjects in terms of augmented pain experience. Furthermore, our previous studies revealed that patients with major depressive disorder showed increased heat pain thresholds on the skin. Potential neurofunctional correlates of this finding were located within the fronto-thalamic network. The aim of the present study was to investigate the neurofunctional underpinnings of the influence of sad mood upon heat pain processing in healthy subjects. For this purpose, we used a combination of the Velten Mood Induction procedure and a piece of music to induce sad affect. Initially we assessed heat pain threshold after successful induction of sad mood outside the MR scanner in Experiment 1. We found a highly significant reduction in heat pain threshold on the left hand and a trend for the right. In Experiment 2, we applied thermal pain stimuli on the left hand (37, 42, and 45 degrees C) in an MRI scanner. Subjects were scanned twice, one group before and after sad-mood induction and another group before and after neutral-mood induction, respectively. Our main finding was a significant group x mood-induction interaction bilaterally in the ventrolateral nucleus of the thalamus indicating a BOLD signal increase after sad-mood induction and a BOLD signal decrease in the control group. We present evidence that induced sad affect leads to reduced heat pain thresholds in healthy subjects. This is probably due to altered lateral thalamic activity, which is potentially associated with changed attentional processes. PMID:19027763

  13. Pleomorphism and acetylene-reducing activity of free-living rhizobia.

    PubMed Central

    Kaneshiro, T; Baker, F L; Johnson, D E

    1983-01-01

    Cowpea-type Rhizobium sp. strain 32H1 and Rhizobium japonicum USDA 26 and 110 grown on a glutamate-mannitol-gluconate agar medium showed increases in the number of pleomorphic cells coincident with their acetylene-reducing activity. Pleomorphs appeared to be inhibited in growth nonuniformly, because acetylene-reducing cultures were mixtures of rod, branched (V, Y, and T), and other irregularly shaped cells. In contrast, strain USDA 10 consistently failed to reduce acetylene, even though it also could grow and yield pleomorphic cells under various conditions. With minimal inhibitory supplements (5 micrograms per ml of medium) of nalidixic acid and novobiocin as cell division inhibitors, an increase in pleomorphic cells was observed, but the inhibited cultures displayed lower acetylene-reducing activity. A study of pleomorphic cells derived in different ways indicated that not all pleomorphs reduce acetylene. Images PMID:6822472

  14. Solid Waste Educational Resources and Activities: Let's Reduce, Reuse, and Recycle. [CD-ROM].

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Washington, DC. Solid Waste and Emergency Response.

    This contains games, activities, publications, and resources for students and teachers on how to reduce, reuse, recycle, and properly manage waste. It also contains a screen saver featuring runners-up from the Earth Day 2000 art contest. Activities and games include titles such as "Planet Protectors,""Recycle City,""Trash and Climate Change," and…

  15. Recycle Alaska: Reduce, Reuse, Recycle. Activities Handbook, Teacher's Guide, and Student Worksheets.

    ERIC Educational Resources Information Center

    Alaska State Dept. of Education, Juneau.

    Recycling is a very important aspect of conserving the environment for future generations. This guide addresses the topic of litter prevention for the Alaskan environment and contains 42 activities. Activity topics covered include Natural Cycles, Human Interruption of Natural Cycles, Reduce, Reuse, Recycle and Recycled Classroom. Grade level,…

  16. A novel technology to increase antioxidant activity of an antioxidant by reducing volatility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During frying, an antioxidant is lost by reaction with radicals for its antioxidant activity, but it is also lost by decomposition and evaporation before it is able to exert antioxidant activity. Some low molecular weight antioxidants are often so volatile that they show much reduced antioxidant act...

  17. Functional activity maps based on significance measures and Independent Component Analysis.

    PubMed

    Martínez-Murcia, F J; Górriz, J M; Ramírez, J; Puntonet, C G; Illán, I A

    2013-07-01

    The use of functional imaging has been proven very helpful for the process of diagnosis of neurodegenerative diseases, such as Alzheimer's Disease (AD). In many cases, the analysis of these images is performed by manual reorientation and visual interpretation. Therefore, new statistical techniques to perform a more quantitative analysis are needed. In this work, a new statistical approximation to the analysis of functional images, based on significance measures and Independent Component Analysis (ICA) is presented. After the images preprocessing, voxels that allow better separation of the two classes are extracted, using significance measures such as the Mann-Whitney-Wilcoxon U-Test (MWW) and Relative Entropy (RE). After this feature selection step, the voxels vector is modelled by means of ICA, extracting a few independent components which will be used as an input to the classifier. Naive Bayes and Support Vector Machine (SVM) classifiers are used in this work. The proposed system has been applied to two different databases. A 96-subjects Single Photon Emission Computed Tomography (SPECT) database from the "Virgen de las Nieves" Hospital in Granada, Spain, and a 196-subjects Positron Emission Tomography (PET) database from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Values of accuracy up to 96.9% and 91.3% for SPECT and PET databases are achieved by the proposed system, which has yielded many benefits over methods proposed on recent works. PMID:23660005

  18. Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.

    PubMed

    Fukui, On; Kinugasa, Yukiko; Fukuda, Aya; Fukuda, Hirotsugu; Tskitishvili, Ekaterine; Hayashi, Shusaku; Song, Mihyon; Kanagawa, Takeshi; Hosono, Takayoshi; Shimoya, Koichiro; Murata, Yuji

    2006-11-22

    Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in

  19. Modest Activity of Pomalidomide in Patients with Myelofibrosis and Significant Anemia

    PubMed Central

    Daver, Naval; Shastri, Aditi; Kadia, Tapan; Quintas-Cardama, Alfonso; Jabbour, Elias; Konopleva, Marina; O’Brien, Susan; Pierce, Sherry; Zhou, Lingsha; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2014-01-01

    We evaluated single agent pomalidomide for myelofibrosis-associated anemia. First, 21 patients received pomalidomide 3.0mg/day on 21-day-on/7-day-off schedule. Due to poor tolerance the study was quickly suspended. Second, 29 patients received pomalidomide 0.5mg/day continuously. Three patients (10%) experienced clinical improvement in hemoglobin per International-Working-Group criteria (median time to response 1.6 months; median response duration 6.7 months). Ten patients were RBC-transfusion-dependent per Delphi criteria; 2 (20%) achieved RBC-transfusion-independence (time to response 0.9 months in both; response duration of 8.3 and 15 months). One grade 3/4 toxicity (neutropenia) occurred. Pomalidomide at low dose is well tolerated but has modest clinical activity in myelofibrosis. PMID:23890523

  20. Preparation and characterization of quaternary ammonium chitosan hydrogel with significant antibacterial activity.

    PubMed

    Fan, Lihong; Yang, Jing; Wu, Huan; Hu, Zhihai; Yi, Jiayan; Tong, Jun; Zhu, Xiaoming

    2015-08-01

    Quaternary ammonium chitosan (HACC)/polyvinyl alcohol (PVA)/polyethylene oxide (PEO) hydrogels were prepared using gamma radiation. The chemical structure of the hydrogels was characterized using FT-IR. The results revealed that HACC, PVA and PEO were perfectly compatible and interacted via the hydrogen bonds. As revealed by SEM, scaffolds with a homogeneous interconnected pore structure were obtained after lyophilizing the hydrogels. The influence of different radiation doses and weight ratios on properties including gel content, swelling ability, water evaporation rate and mechanical properties were investigated. It indicated that the hydrogels had the good swelling ability, water evaporation rate and mechanical properties. In vitro antibacterial activity assessment, the hydrogels exhibited a pronounced inhibitory effect against two bacteria (Staphylococcus aureus and Escherichia coli). Therefore, the hydrogels showed a promising potential to be applied as wound dressing. PMID:25895959

  1. Anthocyanins protected hearts against ischemic injury by reducing MMP-2 activity via Akt/P38 pathways

    PubMed Central

    Hao, Jie; Du, Hong; Li, Weiwei; Liu, Fan; Lu, Jingchao; Yang, Xiuchun; Cui, Wei

    2016-01-01

    Growing evidences suggest that there are close associations between anthocyanins and cardiac protection. However, little is known about the detailed roles of anthocyanins in regulating extracellular matrix (ECM) remodeling. Incubation of primary cultured fibroblasts with anthocyanins reduced both intracellular collagen expression and extracellular collagen secretion. Down-regulation of collagen production was also shown in infarcted cardiac tissues after permanent coronary artery ligation in mice treated with anthocyanins. The phosphorylation levels of Akt and/or P-38 were significantly increased by anthocyanins supplementation in primary cultured fibroblasts. Gelatin zymography analysis of matrix metalloproteinase-2 (MMP-2) activity in conditioned medium collected from fibroblasts demonstrated that anthocyanins treatment significantly reduced MMP-2 activity. These results demonstrated that anthocyanins play a role in mediating myocardial ECM remodeling and that the Akt/P-38 pathways mediate these protective effects on hearts. PMID:27158396

  2. Relict landscapes in active mountain belts: their age, interpretation and geodynamic significance

    NASA Astrophysics Data System (ADS)

    van der Beek, Peter

    2010-05-01

    Planar topographic markers have been widely used to infer the topographic and erosional history of mountain belts. During the last two decades, attention has focused on high-elevation low-relief surfaces in orogenic belts, the interpretation of which has generated considerable controversy regarding their age, mechanism of formation and tectonic or climatic significance. I will review three case studies to illustrate these issues. In the Pyrenees, high-elevation, low-relief surfaces have been mapped throughout the mountain belt and were suggested to have developed at high elevations due to significant base-level rise as a result of backfilling of the southern foreland basin, which developed under endorheic conditions between Late Eocene and Late Miocene times. Isolation of these surface remnants has been suggested to result from a more erosive climate since the Pliocene. However, an alternative study suggests that such relict landscape elements are restricted to the Eastern Pyrenees, developed at low elevations during the Miocene and were subsequently tectonically uplifted. This second hypothesis appears to be comforted by a suite of thermochronological, stratigraphic and geophysical data from the Eastern Pyrenees. We have used a thermo-kinematic model integrating the existing thermochronometry data from the central Pyrenees to constrain the amount and timing of base-level change in that area and find that, while significant filling and re-excavation of the southern flank must have occurred, the timing of exhumation is Late Miocene rather than Pliocene-Quaternary and the relationship with hypothetical relict landscape elements in the high chain remains unclear. In the western European Alps, widespread high-elevation low-relief surfaces develop close to the interface between crystalline basement and sedimentary cover in the "external crystalline massifs" (e.g., Pelvoux-Ecrins, Belledonne, Aar). These surfaces clearly appear to be lithologically controlled and to have

  3. Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice

    PubMed Central

    Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

    2015-01-01

    Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity. PMID:26283354

  4. [The significance of free radicals and antioxidants due to the load induced by sport activity].

    PubMed

    Holecek, V; Liska, J; Racek, J; Rokyta, R

    2004-01-01

    Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable. PMID:15709642

  5. Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice.

    PubMed

    Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

    2015-09-01

    Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity. PMID:26283354

  6. Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide

    PubMed Central

    2012-01-01

    Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria. PMID:22647642

  7. PPARγ activation reduces ischemia/reperfusion-induced metastasis in a murine model of hepatocellular carcinoma

    PubMed Central

    LIU, YI; LIU, ZHAO; CHEN, YUXIN; XU, KESEN; DONG, JIAHONG

    2016-01-01

    Ischemia/reperfusion (I/R) injury during liver resection or transplantation for the treatment of hepatocellular carcinoma (HCC) may increase the risk of metastasis. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been observed to exert a protective effect against hepatic I/R injury. However, whether PPARγ activation exerts a protective effect against I/R-associated liver metastasis remains unknown. Therefore, the present study aimed to investigate the effects of the PPAR agonist rosiglitazone and the specific PPARγ antagonist GW9662 on tumor metastasis following hepatic I/R. An experimental mouse model of hepatic I/R-induced HCC metastasis was designed in order to determine the effects of I/R on tumor metastasis in the liver. Four groups were established: Sham, control (I/R), rosiglitazone (Ro) and rosiglitazone with GW9662 (Ro + GW) groups. In the latter two groups, the treatments were administered intravenously 1 h prior to the induction of ischemia. Tumor load was measured 12 days after the procedure. Furthermore, tissue analyses were conducted to determine the expression levels of alanine aminotransferase, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, vascular cell adhesion molecule (VCAM)-1, nuclear factor (NF)-κB and PPARγ. Rosiglitazone pretreatment appeared to significantly mitigate hepatic I/R injury, as indicated by serological and histological analysis. The levels of VCAM-1, MPO and MMP-9 expression in the Ro group were significantly reduced at 8 h following ischemia compared with those in the control and Ro + GW groups. In addition, rosiglitazone inhibited the I/R-induced activation of NF-κB, and GW9662 attenuated the inhibitory effect. To the best of our knowledge, the present study is the first to report on the expression and the functional roles of PPARγ in I/R-associated metastasis. Short-term treatment of mice with rosiglitazone, a potent PPARγ agonist, confers protective effects against hepatic I

  8. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    PubMed Central

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Background Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). Aim The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Methods Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Results Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Conclusion Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with

  9. Context-dependent activation of reduced autobiographical memory specificity as an avoidant coping style.

    PubMed

    Debeer, Elise; Raes, Filip; Williams, J Mark G; Hermans, Dirk

    2011-12-01

    According to the affect-regulation hypothesis (Williams et al., 2007), reduced autobiographical memory specificity (rAMS) or overgeneral memory (OGM) might be considered a cognitive avoidance strategy; that is, people learn to avoid the emotionally painful consequences associated with the retrieval of specific negative memories. Based on this hypothesis, one would predict significant negative associations between AMS and avoidant coping. However, studies investigating this prediction have led to equivocal results. In the present study we tested a possible explanation for these contradictory findings. It was hypothesized that rAMS (in part) reflects an avoidant coping strategy, which might only become apparent under certain conditions, that is, conditions that signal the possibility of 'danger.' To test this hypothesis, we assessed AMS and behavioral avoidance but experimentally manipulated the instructions. In the neutral condition, two parallel versions of the Autobiographical Memory Test (AMT) were presented under neutral instructions. In the threat condition, the first AMT was presented under neutral instructions, while the second AMT was presented under 'threat instructions.' Results showed no significant correlations between avoidance and OGM under neutral conditions but significant and markedly stronger correlations under threat conditions, with more avoidance being associated with fewer specific and more categoric memories. In addition, high avoiders showed a stronger reduction in AMS in the threat condition as compared with the neutral condition, while low avoiders showed no such difference between conditions. The data confirm that OGM can be considered as part of a broader avoidant coping style. However, more importantly, they show that, at least in nonclinical individuals, the activation of this coping style may depend on the context. PMID:22142214

  10. Impurity effects on reduced-activation ferritic steels developed for fusion applications

    NASA Astrophysics Data System (ADS)

    Klueh, R. L.; Cheng, E. T.; Grossbeck, M. L.; Bloom, E. E.

    2000-08-01

    Reduced-activation steels are being developed for fusion applications by restricting alloying elements that produce long-lived radioactive isotopes when irradiated in the fusion neutron environment. Another source of long-lived isotopes is the impurities in the steel. To examine this, three heats of reduced-activation martensitic steel were analyzed by inductively coupled plasma mass spectrometry for low-level impurities that compromise the reduced-activation characteristics: a 5-ton heat of modified F82H (F82H-Mod) for which an effort was made during production to reduce detrimental impurities, a 1-ton heat of JLF-1, and an 18-kg heat of ORNL 9Cr-2WVTa. Specimens from commercial heats of modified 9Cr-1Mo and Sandvik HT9 were also analyzed. The objective was to determine the difference in the impurity levels in the F82H-Mod and steels for which less effort was used to ensure purity. Silver, molybdenum, and niobium were found to be the tramp impurities of most importance. The F82H-Mod had the lowest levels, but in some cases the levels were not much different from the other heats. The impurity levels in the F82H-Mod produced with present technology did not achieve the low-activation limits for either shallow land burial or recycling. The results indicate the progress that has been made and what still must be done before the reduced-activation criteria can be achieved.

  11. The Lipid Portion of Activated Platelet-Rich Plasma Significantly Contributes to Its Wound Healing Properties

    PubMed Central

    Hoeferlin, Lauren Alexis; Huynh, Quoc K.; Mietla, Jennifer A.; Sell, Scott A.; Tucker, Jason; Chalfant, Charles Edward; Wijesinghe, Dayanjan Shanaka

    2015-01-01

    Objective: Platelet-rich plasma (PRP) is a popular choice for the treatment of chronic wounds. Current dogma attributes these healing properties to the peptide growth factors of PRP. However, PRP is also rich in bioactive lipids whose contribution to healing has not been characterized and warrants investigation due to the protease-rich environment of chronic wounds. Approach: The lipid fraction of PRP was tested with respect to proliferation and migration of primary adult human dermal fibroblasts (HDFa)±exposure to chronic wound fluid (CWF). This fraction was also characterized via LC-MS/MS for bioactive lipids. A synthetic formulation of the bioactive lipid composition was developed and tested for the ability to overcome proliferative growth arrest induced by CWF. Results: The data demonstrate the ability of the lipid fraction of PRP to significantly enhance the migration and proliferation of HDFa, and to overcome the proliferative growth arrest induced by CWF. Furthermore, the synthetic lipid formulation generated following characterization of the PRP lipidome demonstrated a similar ability to overcome proliferative arrest of HDFa in the presence of CWF. Innovation: For the first time, we demonstrate the relevance of the lipid fraction of PRP toward the biology of wound healing. These studies open the possibility of altering the lipid profile of PRP via diet or exogenous pathway manipulation to obtain a better healing outcome. Conclusion: The lipid fraction of PRP is under investigated and yet relevant component in wound healing. The current study demonstrates the relevance of this fraction in wound healing by PRP. PMID:25713752

  12. Drug and food-deprivation modulation of activity in rats given chronic dietary lead: significance of type of activity measure.

    PubMed

    Yamamoto, B K; Kutscher, C L

    1981-09-01

    In Experiment 1, rats were given a 1% lead acetate diet from Day 100 of life to the termination of the experiment. After 82 days of lead feeding behavioral tests were started. Lead exposure increased wheel-turning hyperactivity produced by food deprivation and phenylethylamine injection. Lead produced no activity change in the unchallenged condition. In the open field, lead-exposure rats were less responsive to the stimulating action of PEA and amphetamine and to the sedating action of pentobarbital. In Experiment 2, the interaction of lead with food deprivation of PEA on wheel-turning was replicated in naive animals given only a 32-day exposure. Chemical analysis was made of tissues. Ingested lead entered the brain. Regional steady-state levels of brain norepinephrine, dopamine and serotonin were not altered by lead treatment when measured following four days of starvation at a time when lead-induced behavioral change was distinct. It was concluded that pharmacological challenges on activity may be sensitive indicators of lead exposure, but the type of activity measure is critical. PMID:7291253

  13. Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer.

    PubMed

    Dinpajooh, Mohammadhasan; Martin, Daniel R; Matyushov, Dmitry V

    2016-01-01

    Enzymes in biology's energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work. PMID:27306204

  14. Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer

    NASA Astrophysics Data System (ADS)

    Dinpajooh, Mohammadhasan; Martin, Daniel R.; Matyushov, Dmitry V.

    2016-06-01

    Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work.

  15. Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer

    PubMed Central

    Dinpajooh, Mohammadhasan; Martin, Daniel R.; Matyushov, Dmitry V.

    2016-01-01

    Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work. PMID:27306204

  16. The significance of different health institutions and their respective contributions of active pharmaceutical ingredients to wastewater.

    PubMed

    Herrmann, Manuel; Olsson, Oliver; Fiehn, Rainer; Herrel, Markus; Kümmerer, Klaus

    2015-12-01

    Active pharmaceutical ingredients (APIs) have been frequently found in the environment. It is, however, still not quite clear who is mainly responsible for API emissions. Hospitals have been considered to be the main contributing point sources for wastewater (WW) discharge of APIs. However, recent studies have shown that the contribution of hospitals to the input of APIs into the aquatic environment is quite low. Due to demographic change and the increase of psychiatric diseases, health institutions (HIs) such as psychiatric hospitals and nursing homes are likely to be important sources as well, but no data is available in this respect. This study aims to assess the impact of HIs and to provide a methodology to measure their respective contributions. Drawing on pharmaceutical consumption data for the years 2010, 2011, and 2012, this study identified API usage patterns for a psychiatric hospital (146 beds), a nursing home (286 inhabitants), and a general hospital (741 beds), the latter of which comprises three separate locations. All the HIs are located in two sub-regions of a county district with about 400,000 citizens in southwestern Germany. A selection of neurological drugs was quantified in the sewer of these facilities to evaluate the correlation between consumption and emission. The API contribution of HIs was assessed by comparing the specific consumption in the facilities with the consumption in households, expressed as the emission potential (IEP). The study shows that the usage patterns of APIs in the psychiatric hospital and the nursing home were different from the general hospital. Neurological drugs such as anticonvulsants, psycholeptics, and psychoanaleptics were mainly consumed in the psychiatric hospital and the nursing home (74% and 65%, respectively). Predicted and average measured concentrations in the effluent of the investigated HIs differed mostly by less than one order of magnitude. Therefore, the consumption-based approach is a useful method

  17. Significance of an Active Volcanic Front in the Far Western Aleutian Arc

    NASA Astrophysics Data System (ADS)

    Yogodzinski, G. M.; Kelemen, P. B.; Hoernle, K.

    2015-12-01

    Discovery of a volcanic front west of Buldir Volcano, the western-most emergent Aleutian volcano, demonstrates that the surface expression of Aleutian volcanism falls below sea level just west of 175.9° E longitude, but is otherwise continuous from mainland Alaska to Kamchatka. The newly discovered sites of western Aleutian seafloor volcanism are the Ingenstrem Depression, a 60 km-long structural depression just west of Buldir, and an unnamed area 300 km further west, referred to as the Western Cones. These locations fall along a volcanic front that stretches from Buldir to Piip Seamount near the Komandorsky Islands. Western Aleutian seafloor volcanic rocks include large quantities of high-silica andesite and dacite, which define a highly calc-alkaline igneous series and carry trace element signatures that are unmistakably subduction-related. This indicates that subducting oceanic lithosphere is present beneath the westernmost Aleutian arc. The rarity of earthquakes below depths of 200 km indicates that the subducting plate is unusually hot. Some seafloor volcanoes are 6-8 km wide at the base, and so are as large as many emergent Aleutian volcanoes. The seafloor volcanoes are submerged in water depths >3000 m because they sit on oceanic lithosphere of the Bering Sea. The volcanic front is thus displaced to the north of the ridge of arc crust that underlies the western Aleutian Islands. This displacement, which developed since approximately 6 Ma when volcanism was last active on the islands, must be a consequence of oblique convergence in a system where the subducting plate and large blocks of arc crust are both moving primarily in an arc-parallel sense. The result is a hot-slab system where low subduction rates probably limit advection of hot mantle to the subarc, and produce a relatively cool and perhaps stagnant mantle wedge. The oceanic setting and highly oblique subduction geometry also severely limit rates of sediment subduction, so the volcanic rocks, which

  18. Lung Volume Reduction Surgery and Pulmonary Rehabilitation Improve Exercise Capacity and Reduce Dyspnea During Functional Activities in People with Emphysema

    PubMed Central

    2009-01-01

    Purpose: The purpose of this study was to examine the therapeutic effects of lung volume reduction surgery (LVRS) and pulmonary rehabilitation on levels of dyspnea during functional activities in patients with diffuse emphysema. Methods: Fifteen subjects who had undergone LVRS participated in this study. A visual analog scale (VAS) Activity Dyspnea Scales (VADS) measurement tool developed for this study was determined reliable in 10 subjects. The VADS was used to assess changes in dyspnea with functional activity in 10 subjects prior to and following the interventions of LVRS and pulmonary rehabilitation. Results: Results of this study indicate that LVRS followed by pulmonary rehabilitation significantly reduces levels of dyspnea during functional activities. Conclusion: The VADS developed for this study is a valid and reliable method of assessing changes in levels of dyspnea during functional activities in the LVRS population. PMID:20467532

  19. Inhibition of histone deacetylase activity in reduced oxygen environment enhances the osteogenesis of mouse adipose-derived stromal cells.

    PubMed

    Xu, Yue; Hammerick, Kyle E; James, Aaron W; Carre, Antoine L; Leucht, Philipp; Giaccia, Amato J; Longaker, Michael T

    2009-12-01

    Recent studies suggest that oxygen tension has a great impact on the osteogenic differentiation capacity of mesenchymal cells derived from adipose tissue: reduced oxygen impedes osteogenesis. We have found that expansion of mouse adipose-derived stromal cells (mASCs) in reduced oxygen tension (10%) results in increased cell proliferation along with induction of histone deacetylase (HDAC) activity. In this study, we utilized two HDAC inhibitors (HDACi), sodium butyrate (NaB) and valproic acid (VPA), and studied their effects on mASCs expanded in various oxygen tensions (21%, 10%, and 1% O(2)). Significant growth inhibition was observed with NaB or VPA treatment in each oxygen tension. Osteogenesis was enhanced by treatment with NaB or VPA, particularly in reduced oxygen tensions (10% and 1% O(2)). Conversely, adipogenesis was decreased with treatments of NaB or VPA at all oxygen tensions. Finally, NaB- or VPA-treated, reduced oxygen tension-exposed (1% O(2)) ASCs were grafted into surgically created mouse tibial defects and resulted in significantly increased bone regeneration. In conclusion, HDACi significantly promote the osteogenic differentiation of mASCs exposed to reduced oxygen tension; HDACi may hold promise for future clinical applications of ASCs for skeletal regeneration. PMID:19505250

  20. Inhibition of Histone Deacetylase Activity in Reduced Oxygen Environment Enhances the Osteogenesis of Mouse Adipose-Derived Stromal Cells

    PubMed Central

    Xu, Yue; Hammerick, Kyle E.; James, Aaron W.; Carre, Antoine L.; Leucht, Philipp; Giaccia, Amato J.

    2009-01-01

    Recent studies suggest that oxygen tension has a great impact on the osteogenic differentiation capacity of mesenchymal cells derived from adipose tissue: reduced oxygen impedes osteogenesis. We have found that expansion of mouse adipose-derived stromal cells (mASCs) in reduced oxygen tension (10%) results in increased cell proliferation along with induction of histone deacetylase (HDAC) activity. In this study, we utilized two HDAC inhibitors (HDACi), sodium butyrate (NaB) and valproic acid (VPA), and studied their effects on mASCs expanded in various oxygen tensions (21%, 10%, and 1% O2). Significant growth inhibition was observed with NaB or VPA treatment in each oxygen tension. Osteogenesis was enhanced by treatment with NaB or VPA, particularly in reduced oxygen tensions (10% and 1% O2). Conversely, adipogenesis was decreased with treatments of NaB or VPA at all oxygen tensions. Finally, NaB- or VPA-treated, reduced oxygen tension–exposed (1% O2) ASCs were grafted into surgically created mouse tibial defects and resulted in significantly increased bone regeneration. In conclusion, HDACi significantly promote the osteogenic differentiation of mASCs exposed to reduced oxygen tension; HDACi may hold promise for future clinical applications of ASCs for skeletal regeneration. PMID:19505250

  1. A proper choice of route significantly reduces air pollution exposure--a study on bicycle and bus trips in urban streets.

    PubMed

    Hertel, Ole; Hvidberg, Martin; Ketzel, Matthias; Storm, Lars; Stausgaard, Lizzi

    2008-01-15

    A proper selection of route through the urban area may significantly reduce the air pollution exposure. This is the main conclusion from the presented study. Air pollution exposure is determined for two selected cohorts along the route going from home to working place, and back from working place to home. Exposure is determined with a street pollution model for three scenarios: bicycling along the shortest possible route, bicycling along the low exposure route along less trafficked streets, and finally taking the shortest trip using public transport. Furthermore, calculations are performed for the cases the trip takes place inside as well as outside the traffic rush hours. The results show that the accumulated air pollution exposure for the low exposure route is between 10% and 30% lower for the primary pollutants (NO(x) and CO). However, the difference is insignificant and in some cases even negative for the secondary pollutants (NO(2) and PM(10)/PM(2.5)). Considering only the contribution from traffic in the travelled streets, the accumulated air pollution exposure is between 54% and 67% lower for the low exposure route. The bus is generally following highly trafficked streets, and the accumulated exposure along the bus route is therefore between 79% and 115% higher than the high exposure bicycle route (the short bicycle route). Travelling outside the rush hour time periods reduces the accumulated exposure between 10% and 30% for the primary pollutants, and between 5% and 20% for the secondary pollutants. The study indicates that a web based route planner for selecting the low exposure route through the city might be a good service for the public. In addition the public may be advised to travel outside rush hour time periods. PMID:17936337

  2. Paricalcitol Reduces Peritoneal Fibrosis in Mice through the Activation of Regulatory T Cells and Reduction in IL-17 Production

    PubMed Central

    González-Mateo, Guadalupe T.; Fernández-Míllara, Vanessa; Bellón, Teresa; Liappas, Georgios; Ruiz-Ortega, Marta; López-Cabrera, Manuel; Selgas, Rafael; Aroeira, Luiz S.

    2014-01-01

    Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR) that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice. PMID:25279459

  3. Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production.

    PubMed

    González-Mateo, Guadalupe T; Fernández-Míllara, Vanessa; Bellón, Teresa; Liappas, Georgios; Ruiz-Ortega, Marta; López-Cabrera, Manuel; Selgas, Rafael; Aroeira, Luiz S

    2014-01-01

    Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR) that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice. PMID:25279459

  4. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration

    PubMed Central

    Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70–71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions. PMID:27333203

  5. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta.

    PubMed

    Yan, Zhen Cheng; Liu, Dao Yan; Zhang, Li Li; Shen, Chen Yi; Ma, Qun Li; Cao, Ting Bing; Wang, Li Juan; Nie, Hai; Zidek, Walter; Tepel, Martin; Zhu, Zhi Ming

    2007-03-01

    Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p<0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p<0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-delta. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-delta. Furthermore, selective silencing of PPAR-delta by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00+/-0.06 (n=3) to 1.91+/-0.06 (n=3; p<0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-delta significantly reduced CB1 expression to 0.39+/-0.03 (n=3; p<0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-delta. Both CB1 and PPAR-delta are intimately involved in therapeutic interventions against a most important cardiovascular risk factor. PMID:17223076

  6. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-{delta}

    SciTech Connect

    Yan Zhencheng; Liu Daoyan; Zhang Lili; Shen Chenyi; Ma Qunli; Cao Tingbing; Wang Lijuan; Nie Hai; Zidek, Walter; Tepel, Martin; Zhu Zhiming . E-mail: zhuzm@yahoo.com

    2007-03-09

    Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-{delta} (PPAR-{delta})-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p < 0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p < 0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-{delta}. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-{delta}. Furthermore, selective silencing of PPAR-{delta} by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00 {+-} 0.06 (n = 3) to 1.91 {+-} 0.06 (n = 3; p < 0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-{delta} significantly reduced CB1 expression to 0.39 {+-} 0.03 (n = 3; p < 0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-{delta}. Both CB1 and PPAR-{delta} are intimately involved in therapeutic interventions against a most important cardiovascular risk factor.

  7. Cross-person activity recognition using reduced kernel extreme learning machine.

    PubMed

    Deng, Wan-Yu; Zheng, Qing-Hua; Wang, Zhong-Min

    2014-05-01

    Activity recognition based on mobile embedded accelerometer is very important for developing human-centric pervasive applications such as healthcare, personalized recommendation and so on. However, the distribution of accelerometer data is heavily affected by varying users. The performance will degrade when the model trained on one person is used to others. To solve this problem, we propose a fast and accurate cross-person activity recognition model, known as TransRKELM (Transfer learning Reduced Kernel Extreme Learning Machine) which uses RKELM (Reduced Kernel Extreme Learning Machine) to realize initial activity recognition model. In the online phase OS-RKELM (Online Sequential Reduced Kernel Extreme Learning Machine) is applied to update the initial model and adapt the recognition model to new device users based on recognition results with high confidence level efficiently. Experimental results show that, the proposed model can adapt the classifier to new device users quickly and obtain good recognition performance. PMID:24513850

  8. Occurrence and activity of sulphate reducing bacteria in aerobic activated sludge systems.

    PubMed

    van den Brand, T P H; Roest, K; Chen, G H; Brdjanovic, D; van Loosdrecht, M C M

    2015-03-01

    In the sewage or wastewater treatment plant, biological sulphate reduction can occur spontaneously or be applied beneficially for its treatment. The results of this study can be applied to control SRB in the sewage and WWTP. Therefore, population diversity analyses of SRB for nine activated sludge wastewater treatment plants (WWTP) in the Netherlands and the effect of long-term (months) oxygen exposures on the SRB activity were carried out. T-RFLP and clone sequencing analyses of winter and summer samples revealed that (1) all WWTP have a similar SRB population, (2) there is no seasonal impact (10-20 °C) on the SRB population present in the WWTP and (3) Desulfobacter postgatei, Desulfovibrio desulfuricans and Desulfovibrio intestinalis were the most common and dominant SRB species observed in these samples, and origin from the sewage. Short term activity tests demonstrated that SRB were not active in the aerobic WWTP, but while flushed with N2-gas SRB became slightly active after 3 h. In a laboratory reactor at a dissolved oxygen concentration of <2 %, sulphate reduction occurred and 89 % COD removal was achieved. SRB grew in granules, in order to protect themselves for oxygen exposures. SRB are naturally present in aerobic WWTP, which is due to the formation of granules. PMID:25649202

  9. Polyphenols from Chilean Propolis and Pinocembrin Reduce MMP-9 Gene Expression and Activity in Activated Macrophages

    PubMed Central

    Saavedra, Nicolás; Cuevas, Alejandro; Cavalcante, Marcela F.; Dörr, Felipe A.; Saavedra, Kathleen; Zambrano, Tomás; Abdalla, Dulcineia S. P.; Salazar, Luis A.

    2016-01-01

    Polyphenols from diverse sources have shown anti-inflammatory activity. In the context of atherosclerosis, macrophages play important roles including matrix metalloproteinases synthesis involved in degradation of matrix extracellular components affecting the atherosclerotic plaque stability. We prepared a propolis extract and pinocembrin in ethanol solution. Propolis extract was chemically characterized using LC-MS. The effect of treatments on gene expression and proteolytic activity was measured in vitro using murine macrophages activated with LPS. Cellular toxicity associated with both treatments and the vehicle was determined using MTT and apoptosis/necrosis detection assays. MMP-9 gene expression and proteolytic activity were measured using qPCR and zymography, respectively. Thirty-two compounds were identified in the propolis extract, including pinocembrin among its major components. Treatment with either ethanolic extract of propolis or pinocembrin inhibits MMP-9 gene expression in a dose-dependent manner. Similarly, an inhibitory effect was observed in proteolytic activity. However, the effect showed by ethanolic extract of propolis was higher than the effect of pinocembrin, suggesting that MMP-9 inhibition results from a joint contribution between the components of the extract. These data suggest a potential role of polyphenols from Chilean propolis in the control of extracellular matrix degradation in atherosclerotic plaques. PMID:27119082

  10. Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador

    PubMed Central

    Anselmi, Mariella; Buonfrate, Dora; Guevara Espinoza, Angel; Prandi, Rosanna; Marquez, Monica; Gobbo, Maria; Montresor, Antonio; Albonico, Marco; Racines Orbe, Marcia; Bisoffi, Zeno

    2015-01-01

    Objectives To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. Methods We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). Results In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. Conclusions Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID:26540412

  11. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions.

    PubMed

    Zhu, Li; Yang, Zhong-Cheng; Li, Ao; Cheng, De-Chang

    2000-02-01

    AIM:To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS:A rat model with 30% TBSA full thickness burn injury was employed and the gastric acid production,together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48h postburn.RESULTS:The gastric acid production in the acute shock period was markedly inhibited after severe burn injury.At the 3rd h postburn,the gastric juice volume, total acidity and acid output were already significantly decreased (P < 0.01 =, and reached the lowest point, 0.63mL/L ± 0.20mL/L, 10.81mmol/L ± 2.58mmol/L and 2.23mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION:Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment. PMID:11819529

  12. Comparison of two methods for assaying reducing sugars in the determination of carbohydrase activities.

    PubMed

    Gusakov, Alexander V; Kondratyeva, Elena G; Sinitsyn, Arkady P

    2011-01-01

    The Nelson-Somogyi (NS) and 3,5-dinitrosalicylic acid (DNS) assays for reducing sugars are widely used in measurements of carbohydrase activities against different polysaccharides. Using twelve commercial enzyme preparations, the comparison of the NS and DNS assays in determination of cellulase, β-glucanase, xylanase, and β-mannanase activities was carried out. When cellulase activities against CMC were measured, the DNS assay gave activity values, which were typically 40-50% higher than those obtained with the NS assay. In the analysis of the xylanase, β-mannanase, and β-glucanase activities, the overestimations by the DNS assay were much more pronounced (the observed differences in the activities were 3- to 13-fold). Reasons for preferential use of the NS assay for measuring activities of carbohydrases other than cellulases are discussed. PMID:21647284

  13. Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model.

    PubMed

    Hara, Yuta; Takuma, Kazuhiro; Takano, Erika; Katashiba, Keisuke; Taruta, Atsuki; Higashino, Kosuke; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

    2015-08-01

    Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way. PMID:25907743

  14. BiPO4/reduced graphene oxide composites photocatalyst with high photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Zhang, Yihe; Shen, Bo; Huang, Hongwei; He, Ying; Fei, Bin; Lv, Fengzhu

    2014-11-01

    The composite photocatalysts composed of BiPO4 and reduced graphene oxide (rGO) were synthesized by a facile hydrothermal method. Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), transmission electron spectroscopy (TEM), photoluminescence emission spectra (PL) and UV-vis diffuse reflection spectroscopy (DRS) were used to characterize the titled composites. The results showed that the BiPO4 particles can be immobilized on the surface of rGO sheets, and the crystallization phases of BiPO4 were significantly influenced by the amount of graphene. The phase transformation of BiPO4 crystal from hexagonal to monoclinic phase was observed. The introduction of rGO improved the optical properties of BiPO4 and thereby enhancing the utilization of light. Compared with pure BiPO4 under similar synthesis condition, the BiPO4/rGO composites exhibit a much higher photodegradation activity, which was confirmed by photoluminescence (PL) spectra and photocurrent (PC) generation.

  15. In situ treatment with activated carbon reduces bioaccumulation in aquatic food chains.

    PubMed

    Kupryianchyk, D; Rakowska, M I; Roessink, I; Reichman, E P; Grotenhuis, J T C; Koelmans, A A

    2013-05-01

    In situ activated carbon (AC) amendment is a new direction in contaminated sediment management, yet its effectiveness and safety have never been tested on the level of entire food chains including fish. Here we tested the effects of three different AC treatments on hydrophobic organic chemical (HOC) concentrations in pore water, benthic invertebrates, zooplankton, and fish (Leuciscus idus melanotus). AC treatments were mixing with powdered AC (PAC), mixing with granular AC (GAC), and addition-removal of GAC (sediment stripping). The AC treatments resulted in a significant decrease in HOC concentrations in pore water, benthic invertebrates, zooplankton, macrophytes, and fish. In 6 months, PAC treatment caused a reduction of accumulation of polychlorobiphenyls (PCB) in fish by a factor of 20, bringing pollutant levels below toxic thresholds. All AC treatments supported growth of fish, but growth was inhibited in the PAC treatment, which was likely explained by reduced nutrient concentrations, resulting in lower zooplankton (i.e., food) densities for the fish. PAC treatment may be advised for sites where immediate ecosystem protection is required. GAC treatment may be equally effective in the longer term and may be adequate for vulnerable ecosystems where longer-term protection suffices. PMID:23544454

  16. Effect of silicon on the microstructure and mechanical properties of reduced activation ferritic/martensitic steel

    NASA Astrophysics Data System (ADS)

    Chen, Shenghu; Rong, Lijian

    2015-04-01

    The effect of Si in the range of 0.05-0.77 wt.% on the microstructure, tensile properties and impact toughness of reduced activation ferritic/martensitic (RAFM) steels has been investigated. An increase in Si content affected the prior austenite grain size resulting in an increase in the tensile strength at room temperature. The tensile strength of steels tested above 773 K did not change significantly with the addition of Si, which was due to the diminished carbide hardening effect and boundary strengthening effect. Detailed fractographic analysis revealed that tear fractures occurred in the samples tensile tested at room temperature, while cup and cone fractures were found in samples tensile tested at temperatures above 773 K, which were induced by the easing of dislocation pile-ups. The ductile-to-brittle transition temperature (DBTT) decreased when the Si content increased to 0.22 wt.%. However, the DBTT increased when the Si content reached 0.77 wt.% and this was due to the precipitation of Laves phase. The RAFM steel with approximately 0.22 wt.% Si content was found to possess an optimized combination of microstructure, tensile properties and impact toughness.

  17. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury.

    PubMed

    Harvey, Lloyd D; Yin, Yan; Attarwala, Insiya Y; Begum, Gulnaz; Deng, Julia; Yan, Hong Q; Dixon, C Edward; Sun, Dandan

    2015-01-01

    We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1(+) microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32(+) microglia or macrophages, but an increased CD206(+) phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1(+) microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1(+) microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic

  18. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury

    PubMed Central

    Harvey, Lloyd D.; Yin, Yan; Attarwala, Insiya Y.; Begum, Gulnaz; Deng, Julia; Yan, Hong Q.; Dixon, C. Edward

    2015-01-01

    We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1+ microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32+ microglia or macrophages, but an increased CD206+ phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1+ microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1+ microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to

  19. Pomalidomide Shows Significant Therapeutic Activity against CNS Lymphoma with a Major Impact on the Tumor Microenvironment in Murine Models

    PubMed Central

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A.; Moghaddam, Mehran F.; Copland, John A.; Tun, Han W.

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  20. Inactivation of mitogen-activated protein kinase signaling pathway reduces caspase-14 expression in impaired keratinocytes

    PubMed Central

    Dang, Ningning; Pang, Shuguang; Song, Haiyan; An, Liguo; Ma, Xiaoli

    2016-01-01

    Objective(s): Several investigations have revealed that caspase-14 is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the possible mechanism that contributes to the regulation of caspase-14. Materials and Methods: The filaggrin-deficient NHEKs were induced by transfection with lentivirus (LV) vector encoding small hairpin RNAs (shRNA). The inhibitors SB203580, PD98059 and SP600125 were used for suppressing the expression of p38 mitogen-activated protein kinase (MAPK), p44/42 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The expression of filaggrin, p38 MAPK, p44/42 MAPK and SAPK/JNK, caspase-14, keratin1and keratin2 were detected by western blot. Results: In filaggrin-deficient NHEKs, the expression of p38, p44/42 MAPK and SAPK/JNK and caspase-14 were significantly decreased. The inhibition of p38 and SAPK/JNK reduced the expression of caspase-14, while the p44/42 MAPK showed no consistent effects. Moreover, the filaggrin knockdown decreased the expression of keratin2, but had no effects on the level of keratin1. Conclusion: The decreased expression of caspase-14 in filaggrin-deficient NHEKs may be induced by the inactivation of MAPK signaling pathway. These provide a novel perspective to understand the mechanism for the protective effects of filaggrin and caspase-14 on skin barrier function. PMID:27096061

  1. Effects of nanomaterials on luciferase with significant protection and increased enzyme activity observed for zinc oxide nanomaterials.

    PubMed

    Barber, S; Abdelhakiem, M; Ghosh, K; Mitchell, L; Spidle, R; Jacobs, B; Washington, L; Li, J; Wanekaya, A; Glaspell, G; DeLong, R K

    2011-12-01

    This principle goal of this research was to examine the effects of various nanomaterials on the activity and behavior of the firefly enzyme luciferase. Nanomaterials have been found to stabilize, and in some instances, shown to increase the activity of enzymes. In this study gold, manganese oxide (MnO), and zinc oxide (ZnO) nanomaterials were utilized in order to test their effects on enzyme activity. Luciferase was used because its activity is easy to analyze, as it typically produces a large amount of bioluminescence easily detected by a Microtiter plate reader. Following incubation with the various nanomaterials, luciferase was subjected to degradation by several protein denaturing agents, such as heat, SDS, urea, ethanol, protease, hydrogen peroxide, and pH changes. Results indicated that luciferase activity is indeed affected when combined with nanomaterials, accompanied by both increases and decreases in enzyme activity depending on the type of nanomaterial and denaturing agent used. In most of the experiments, when incubated with ZnO nanomaterials, luciferase depicted significant increases in activity and bioluminescence. Additional experiments, in which human A375 cells were treated with luciferase-nanomaterial mixtures, also depicted increased enzyme activity and bioluminescence for luciferase incubated with ZnO nanomaterials. Ultimately, our findings indicated that when luciferase was subjected to multiple types of denaturation, zinc oxide nanomaterials dramatically preserved and increased enzyme activity and bioluminescence. PMID:22408903

  2. Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects

    NASA Technical Reports Server (NTRS)

    Carter, Jason R.; Ray, Chester A.; Downs, Emily M.; Cooke, William H.

    2003-01-01

    The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.

  3. Increased physical activity has a greater effect than reduced energy intake on lifestyle modification-induced increases in testosterone.

    PubMed

    Kumagai, Hiroshi; Zempo-Miyaki, Asako; Yoshikawa, Toru; Tsujimoto, Takehiko; Tanaka, Kiyoji; Maeda, Seiji

    2016-01-01

    Obesity has reached epidemic proportions worldwide. Obesity results in reduced serum testosterone levels, which causes many disorders in men. Lifestyle modifications (increased physical activity and calorie restriction) can increase serum testosterone levels. However, it is unknown whether increased physical activity or calorie restriction during lifestyle modifications has a greater effects on serum testosterone levels. Forty-one overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and calorie restriction). We measured serum testosterone levels, the number of steps, and the total energy intake. We divided participants into two groups based on the median change in the number of steps (high or low physical activities) or that in calorie restriction (high or low calorie restrictions). After the program, serum testosterone levels were significantly increased. Serum testosterone levels in the high physical activity group were significantly higher than those in the low activity group. This effect was not observed between the groups based on calorie restriction levels. We found a significant positive correlation between the changes in serum testosterone levels and the number of steps. Our results suggested that an increase in physical activity greatly affected the increased serum testosterone levels in overweight and obese men during lifestyle modification. PMID:26798202

  4. Assessment of xylanase activity in dry storage as a potential method of reducing feedstock cost.

    PubMed

    Smith, William A; Thompson, David N; Thompson, Vicki S; Radtke, Corey W; Carter, Brady

    2009-05-01

    Enzymatic preprocessing of lignocellulosic biomass in dry storage systems has the potential to improve feedstock characteristics and lower ethanol production costs. To assess the potential for endoxylanase activity at low water contents, endoxylanase activity was tested using a refined wheat arabinoxylan substrate and three commercial endoxylanases over the water activity range 0.21-1.0, corresponding to water contents of 5% to >60% (dry basis). Homogeneously mixed dry samples were prepared at a fixed enzyme to substrate ratio and incubated in chambers at a variety of fixed water activities. Replicates were sacrificed periodically, and endoxylanase activity was quantified as an increase in reducing sugar relative to desiccant-stored controls. Endoxylanase activity was observed at water activities over 0.91 in all enzyme preparations in less than 4 days and at a water activity of 0.59 in less than 1 week in two preparations. Endoxylanase activity after storage was confirmed for selected desiccant-stored controls by incubation at 100% relative humidity. Water content to water activity relationships were determined for three lignocellulosic substrates, and results indicate that two endoxylanase preparations retained limited activity as low as 7% to 13% water content (dry basis), which is well within the range of water contents representative of dry biomass storage. Future work will examine the effects of endoxylanase activity toward substrates such as corn stover, wheat straw, and switchgrass in low water content environments. PMID:19096939

  5. Extensive sugar modification improves triple helix forming oligonucleotide activity in vitro but reduces activity in vivo.

    PubMed

    Alam, Md Rowshon; Majumdar, Alokes; Thazhathveetil, Arun Kalliat; Liu, Su-Ting; Liu, Ji-Lan; Puri, Nitin; Cuenoud, Bernard; Sasaki, Shigeki; Miller, Paul S; Seidman, Michael M

    2007-09-01

    We are developing triple helix forming oligonucleotides (TFOs) for gene targeting. Previously, we synthesized bioactive TFOs containing 2'-O-methylribose (2'-OMe) and 2'-O-aminoethylribose (2'-AE) residues. Active TFOs contained four contiguous 2'-AE residues and formed triplexes with high thermal stability and rapid association kinetics. In an effort to further improve bioactivity, we synthesized three series of TFOs containing the 2'-AE patch and additional ribose modifications distributed throughout the remainder of the oligonucleotide. These were either additional 2'-AE residues, the conformationally locked BNA/LNA ribose with a 2'-O,4'-C-methylene bridge, or the 2'-O,4'-C-ethylene analogue (ENA). The additionally modified TFOs formed triplexes with greater thermal stability than the reference TFO, and some had improved association kinetics. However, the most active TFOs in the biochemical and biophysical assays were the least active in the bioassay. We measured the thermal stability of triplexes formed by the TFOs in each series on duplex targets containing a change in sequence at a single position. The Tm value of the variant sequence triplexes increased as the number of all additional modifications increased. A simple explanation for the failure of the improved TFOs in the bioassay was that the increased affinity for nonspecific targets lowered the effective nuclear concentration. Enhancement of TFO bioactivity will require chemical modifications that improve interaction with the specific targets while retaining selectivity against mismatched sequences. PMID:17691818

  6. Transfection of Sclerotinia sclerotiorum with In Vitro Transcripts of a Naturally Occurring Interspecific Recombinant of Sclerotinia sclerotiorum Hypovirus 2 Significantly Reduces Virulence of the Fungus

    PubMed Central

    Marzano, Shin-Yi Lee; Hobbs, Houston A.; Nelson, Berlin D.; Hartman, Glen L.; Eastburn, Darin M.; McCoppin, Nancy K.

    2015-01-01

    ABSTRACT A recombinant strain of Sclerotinia sclerotiorum hypovirus 2 (SsHV2) was identified from a North American Sclerotinia sclerotiorum isolate (328) from lettuce (Lactuca sativa L.) by high-throughput sequencing of total RNA. The 5′- and 3′-terminal regions of the genome were determined by rapid amplification of cDNA ends. The assembled nucleotide sequence was up to 92% identical to two recently reported SsHV2 strains but contained a deletion near its 5′ terminus of more than 1.2 kb relative to the other SsHV2 strains and an insertion of 524 nucleotides (nt) that was distantly related to Valsa ceratosperma hypovirus 1. This suggests that the new isolate is a heterologous recombinant of SsHV2 with a yet-uncharacterized hypovirus. We named the new strain Sclerotinia sclerotiorum hypovirus 2 Lactuca (SsHV2L) and deposited the sequence in GenBank with accession number KF898354. Sclerotinia sclerotiorum isolate 328 was coinfected with a strain of Sclerotinia sclerotiorum endornavirus 1 and was debilitated compared to cultures of the same isolate that had been cured of virus infection by cycloheximide treatment and hyphal tipping. To determine whether SsHV2L alone could induce hypovirulence in S. sclerotiorum, a full-length cDNA of the 14,538-nt viral genome was cloned. Transcripts corresponding to the viral RNA were synthesized in vitro and transfected into a virus-free isolate of S. sclerotiorum, DK3. Isolate DK3 transfected with SsHV2L was hypovirulent on soybean and lettuce and exhibited delayed maturation of sclerotia relative to virus-free DK3, completing Koch's postulates for the association of hypovirulence with SsHV2L. IMPORTANCE A cosmopolitan fungus, Sclerotinia sclerotiorum infects more than 400 plant species and causes a plant disease known as white mold that produces significant yield losses in major crops annually. Mycoviruses have been used successfully to reduce losses caused by fungal plant pathogens, but definitive relationships between

  7. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

    PubMed

    Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

    2015-11-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis. PMID:26485286

  8. High salt reduces the activation of IL-4– and IL-13–stimulated macrophages

    PubMed Central

    Binger, Katrina J.; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A.; Lang, Florian; Voehringer, David; Wright, Mark D.; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N.

    2015-01-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt–induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis. PMID:26485286

  9. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke–Induced COPD in C57BL/6 mice

    PubMed Central

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; Ligeiro de Oliveira, Ana Paula

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J—660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  10. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    PubMed

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  11. Initial Evaluation of Active Minds: A Student Organization Dedicated to Reducing the Stigma of Mental Illness

    ERIC Educational Resources Information Center

    McKinney, Kathleen G.

    2009-01-01

    This study examined whether a new student organization, Active Minds, aimed at increasing awareness of "mental illness" and reducing stigma had an impact on students' stigma and willingness to seek psychological help. Three classes were recruited to become involved in the organization. In a pretest/posttest design, stigma and willingness to seek…

  12. Integrated Health and Physical Education Program to Reduce Media Use and Increase Physical Activity in Youth

    ERIC Educational Resources Information Center

    Clocksin, Brian D.; Wattson, Doris L.; Williams, Daniel P.; Randsell, Lynda

    2009-01-01

    The purpose of this project was to compare an integrated health and physical education curriculum, focused on reducing media use and on increasing physical activity in middle school adolescents, to traditional and nonintegrated health and physical education curricula. Two middle schools' health and physical education classes were assigned to an…

  13. Seasonal composition and activity of sulfate-reducing prokaryotic communities in seagrass bed sediments

    EPA Science Inventory

    Sulfate-reducing prokaryotes (SRP) play a key role in the carbon and nutrient cycles of coastal marine, vegetated ecosystems, but the interactions of SRP communities with aquatic plants remain little studied. The abundance, activity, and community composition of SRP was studied i...

  14. Empowering Sedentary Adults to Reduce Sedentary Behavior and Increase Physical Activity Levels and Energy Expenditure: A Pilot Study

    PubMed Central

    Barwais, Faisal A.; Cuddihy, Thomas F.

    2015-01-01

    Objective: The purpose of this study was to assess the effectiveness of a 4-week intervention in which an online personal activity monitor (Gruve-Technologies™) was used to reduce sedentary behavior among sedentary adults. Method: Eighteen, sedentary adult volunteers (12 men, six women, mean age 29 ± 4.0 years) were recruited to participate in the study. Time spent in sedentary activities and light-, moderate-, and vigorous-intensity physical activity and energy expenditure were assessed during waking hours using the monitor and the 7-day SLIPA Log at both baseline and post-intervention. Results: A significant decrease of 33% (3.1 h/day; p < 0.001) was found between the time spent in sedentary activities measured at baseline (9.4 ± 1.1 h/day) and at the end of the 4-week intervention (6.3 ± 0.8 h/day). Consequent to the changes in sedentary time, significant increases were found in the amount of time spent in light- (45% (2.6 h/day), p < 0.001), moderate- (33% (1 h/day) p < 0.001), vigorous-intensity physical activity (39% (0.16 h/day), p < 0.001), and energy expenditure (47% (216.7 kcal/day), p < 0.001). Conclusion: This monitor contributes to a meaningful reduction in time spent in sedentary activities and has a large effect on energy expenditure and physical activity patterns. PMID:25568971

  15. A Yersinia pestis-specific, lytic phage preparation significantly reduces viable Y. pestis on various hard surfaces experimentally contaminated with the bacterium.

    PubMed

    Rashid, Mohammed H; Revazishvili, Tamara; Dean, Timothy; Butani, Amy; Verratti, Kathleen; Bishop-Lilly, Kimberly A; Sozhamannan, Shanmuga; Sulakvelidze, Alexander; Rajanna, Chythanya

    2012-07-01

    Five Y. pestis bacteriophages obtained from various sources were characterized to determine their biological properties, including their taxonomic classification, host range and genomic diversity. Four of the phages (YpP-G, Y, R and YpsP-G) belong to the Podoviridae family, and the fifth phage (YpsP-PST) belongs to the Myoviridae family, of the order Caudovirales comprising of double-stranded DNA phages. The genomes of the four Podoviridae phages were fully sequenced and found to be almost identical to each other and to those of two previously characterized Y. pestis phages Yepe2 and φA1122. However, despite their genomic homogeneity, they varied in their ability to lyse Y. pestis and Y. pseudotuberculosis strains. The five phages were combined to yield a "phage cocktail" (tentatively designated "YPP-100") capable of lysing the 59 Y. pestis strains in our collection. YPP-100 was examined for its ability to decontaminate three different hard surfaces (glass, gypsum board and stainless steel) experimentally contaminated with a mixture of three genetically diverse Y. pestis strains CO92, KIM and 1670G. Five minutes of exposure to YPP-100 preparations containing phage concentrations of ca. 10(9), 10(8) and 10(7) PFU/mL completely eliminated all viable Y. pestis cells from all three surfaces, but a few viable cells were recovered from the stainless steel coupons treated with YPP-100 diluted to contain ca. 10(6) PFU/mL. However, even that highly diluted preparation significantly (p = < 0.05) reduced Y. pestis levels by ≥ 99.97%. Our data support the idea that Y. pestis phages may be useful for decontaminating various hard surfaces naturally- or intentionally-contaminated with Y. pestis. PMID:23275868

  16. The chemical digestion of Ti6Al7Nb scaffolds produced by Selective Laser Melting reduces significantly ability of Pseudomonas aeruginosa to form biofilm.

    PubMed

    Junka, Adam F; Szymczyk, Patrycja; Secewicz, Anna; Pawlak, Andrzej; Smutnicka, Danuta; Ziółkowski, Grzegorz; Bartoszewicz, Marzenna; Chlebus, Edward

    2016-01-01

    In our previous work we reported the impact of hydrofluoric and nitric acid used for chemical polishing of Ti-6Al-7Nb scaffolds on decrease of the number of Staphylococcus aureus biofilm forming cells. Herein, we tested impact of the aforementioned substances on biofilm of Gram-negative microorganism, Pseudomonas aeruginosa, dangerous pathogen responsible for plethora of implant-related infections. The Ti-6Al-7Nb scaffolds were manufactured using Selective Laser Melting method. Scaffolds were subjected to chemical polishing using a mixture of nitric acid and fluoride or left intact (control group). Pseudomonal biofilm was allowed to form on scaffolds for 24 hours and was removed by mechanical vortex shaking. The number of pseudomonal cells was estimated by means of quantitative culture and Scanning Electron Microscopy. The presence of nitric acid and fluoride on scaffold surfaces was assessed by means of IR and rentgen spetorscopy. Quantitative data were analysed using the Mann-Whitney test (P ≤ 0.05). Our results indicate that application of chemical polishing correlates with significant drop of biofilm-forming pseudomonal cells on the manufactured Ti-6Al-7Nb scaffolds ( p = 0.0133, Mann-Whitney test) compared to the number of biofilm-forming cells on non-polished scaffolds. As X-ray photoelectron spectroscopy revealed the presence of fluoride and nitrogen on the surface of scaffold, we speculate that drop of biofilm forming cells may be caused by biofilm-supressing activity of these two elements. PMID:27150429

  17. The immune response to vaccinia virus is significantly reduced after scarification with TK- recombinants as compared to wild-type virus.

    PubMed

    Phillpotts, R J; Lescott, T; Gates, A J; Jones, L

    2000-01-01

    Although it is unlikely that large-scale vaccination against smallpox will ever be required again, it is conceivable that the need may arise to vaccinate against a human orthopoxvirus infection. A possible example could be the emergence of monkey poxvirus (MPV) as a significant human disease in Africa. Vaccinia virus (VV) recombinants, genetically modified to carry the immunogenic proteins of other pathogenic organisms, have potential use as vaccines against other diseases present in this region. The immune response to parental wild-type (wt) or recombinant VV was examined by binding and functional assays, relevant to protection: total IgG, IgG subclass profile, B5R gene product (gp42)-specific IgG, neutralizing antibodies and class 1-mediated cytotoxic lymphocyte activity. There was a substantial reduction in the immune response to VV after scarification with about 10(8) PFU of recombinant as compared to wt virus. These data suggest that to achieve the levels of immunity associated with protection against human orthopoxvirus infection, and to control a possible future outbreak of orthopoxvirus disease, the use of wt VV would be necessary. PMID:11155357

  18. Activation of aluminum as an effective reducing agent by pitting corrosion for wet-chemical synthesis.

    PubMed

    Li, Wei; Cochell, Thomas; Manthiram, Arumugam

    2013-01-01

    Metallic aluminum (Al) is of interest as a reducing agent because of its low standard reduction potential. However, its surface is invariably covered with a dense aluminum oxide film, which prevents its effective use as a reducing agent in wet-chemical synthesis. Pitting corrosion, known as an undesired reaction destroying Al and is enhanced by anions such as F⁻, Cl⁻, and Br⁻ in aqueous solutions, is applied here for the first time to activate Al as a reducing agent for wet-chemical synthesis of a diverse array of metals and alloys. Specifically, we demonstrate the synthesis of highly dispersed palladium nanoparticles on carbon black with stabilizers and the intermetallic Cu₂Sb/C, which are promising candidates, respectively, for fuel cell catalysts and lithium-ion battery anodes. Atomic hydrogen, an intermediate during the pitting corrosion of Al in protonic solvents (e.g., water and ethylene glycol), is validated as the actual reducing agent. PMID:23390579

  19. Activation of Aluminum as an Effective Reducing Agent by Pitting Corrosion for Wet-chemical Synthesis

    PubMed Central

    Li, Wei; Cochell, Thomas; Manthiram, Arumugam

    2013-01-01

    Metallic aluminum (Al) is of interest as a reducing agent because of its low standard reduction potential. However, its surface is invariably covered with a dense aluminum oxide film, which prevents its effective use as a reducing agent in wet-chemical synthesis. Pitting corrosion, known as an undesired reaction destroying Al and is enhanced by anions such as F−, Cl−, and Br− in aqueous solutions, is applied here for the first time to activate Al as a reducing agent for wet-chemical synthesis of a diverse array of metals and alloys. Specifically, we demonstrate the synthesis of highly dispersed palladium nanoparticles on carbon black with stabilizers and the intermetallic Cu2Sb/C, which are promising candidates, respectively, for fuel cell catalysts and lithium-ion battery anodes. Atomic hydrogen, an intermediate during the pitting corrosion of Al in protonic solvents (e.g., water and ethylene glycol), is validated as the actual reducing agent. PMID:23390579

  20. Role of plant residues in determining temporal patterns of the activity, size, and structure of nitrate reducer communities in soil.

    PubMed

    Chèneby, D; Bru, D; Pascault, N; Maron, P A; Ranjard, L; Philippot, L

    2010-11-01

    The incorporation of plant residues into soil not only represents an opportunity to limit soil organic matter depletion resulting from cultivation but also provides a valuable source of nutrients such as nitrogen. However, the consequences of plant residue addition on soil microbial communities involved in biochemical cycles other than the carbon cycle are poorly understood. In this study, we investigated the responses of one N-cycling microbial community, the nitrate reducers, to wheat, rape, and alfalfa residues for 11 months after incorporation into soil in a field experiment. A 20- to 27-fold increase in potential nitrate reduction activity was observed for residue-amended plots compared to the nonamended plots during the first week. This stimulating effect of residues on the activity of the nitrate-reducing community rapidly decreased but remained significant over 11 months. During this period, our results suggest that the potential nitrate reduction activity was regulated by both carbon availability and temperature. The presence of residues also had a significant effect on the abundance of nitrate reducers estimated by quantitative PCR of the narG and napA genes, encoding the membrane-bound and periplasmic nitrate reductases, respectively. In contrast, the incorporation of the plant residues into soil had little impact on the structure of the narG and napA nitrate-reducing community determined by PCR-restriction fragment length polymorphism (RFLP) fingerprinting. Overall, our results revealed that the addition of plant residues can lead to important long-term changes in the activity and size of a microbial community involved in N cycling but with limited effects of the type of plant residue itself. PMID:20833788

  1. Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity.

    PubMed

    Wainright, Katherine S; Fleming, Nicholas J; Rowles, Joe L; Welly, Rebecca J; Zidon, Terese M; Park, Young-Min; Gaines, T'Keaya L; Scroggins, Rebecca J; Anderson-Baucum, Emily K; Hasty, Alyssa H; Vieira-Potter, Victoria J; Padilla, Jaume

    2015-09-01

    Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately -24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype. PMID:26180183

  2. Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

    PubMed Central

    Luechinger, Roger; Boesiger, Peter; Rasch, Björn

    2013-01-01

    Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks. PMID:23565239

  3. Modeling prograde TiO2 activity and its significance for Ti-in-quartz thermobarometry of pelitic metamorphic rocks

    NASA Astrophysics Data System (ADS)

    Ashley, Kyle T.; Law, Richard D.

    2015-02-01

    Since its calibration, the Ti-in-quartz thermobarometer has been applied to a wide variety of geologic scenarios. The abundance of quartz in the continental crust and the involvement of silica in metamorphic reactions, deformation, and fluid flux processes make it a particularly powerful tool for constraining the pressure and temperature evolution of rocks, which is essential for developing tectonic models. Being able to quantitatively determine the solubility of Ti in quartz, however, is dependent upon being able to determine the activity of TiO2 in the rock during quartz growth or re-equilibration. Here we calculate TiO2 chemical potentials of the system relative to that of rutile (as a standard state), projected in P- T space for an average sub-aluminous pelite composition. Titania activities are calculated from these dependent potentials, with resultant activities used to correct for Ti isopleth projection in the Thomas et al. (2010) solubility equation. The modeling results are in good agreement with previous studies that suggest ilmenite-bearing assemblages buffer high TiO2 activities and titanite-bearing assemblages have much lower activities (≥0.5). At elevated temperatures, however, significant deviation from an assumed average pelite activity of 1.0 occurs, where the projected Ti concentration in quartz is up to 400 % different when assuming a dynamic system activity. This is due, in part, to the sequestering of Ti in biotite during heating and the destabilization of Ti-oxides at higher temperatures. With quartz-producing reactions, deformation-driven solution-transfer processes and other Si-mobilization events occur during the prograde and retrograde history of metapelites, and assuming TiO2 activities associated with the peak metamorphic paragenesis may be misleading and result in significant errors in P- T calculations.

  4. Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla.

    PubMed

    Zhou, Xiaoming; Wang, Hong; Koles, Nancy L; Zhang, Aihong; Aronson, Naomi E

    2014-09-01

    Visceral leishmaniasis patients have been reported to have a urine concentration defect. Concentration of urine by the renal inner medulla is essentially dependent on a transcription factor, NFAT5/TonEBP, because it activates expression of osmoprotective genes betaine/glycine transporter 1 (BGT1) and sodium/myo-inositol transporter (SMIT), and water channel aquaporin-2, all of which are imperative for concentrating urine. Leishmania parasites evade macrophage immune defenses by activating protein tyrosine phosphatases, among which SHP-1 is critical. We previously demonstrated that SHP-1 inhibits tonicity-dependent activation of NFAT5/TonEBP in HEK293 cells through screening a genome-wide small interfering (si) RNA library against phosphatases (Zhou X, Gallazzini M, Burg MB, Ferraris JD. Proc Natl Acad Sci USA 107: 7072-7077, 2010). We sought to examine whether Leishmania can activate SHP-1 and inhibit NFAT5/TonEBP activity in the renal inner medulla in a murine model of visceral leishmaniasis by injection of female BALB/c mice with a single intravenous dose of 5 × 10(5) L. chagasi metacyclic promastigotes. We found that SHP-1 is expressed in the kidney inner medulla. L. chagasi activates SHP-1 with an increase in stimulatory phosphorylation of SHP-1-Y536 in the region. L. chagasi reduces expression of NFAT5/TonEBP mRNA and protein as well as expression of its targeted genes: BGT1, SMIT, and aquaporin-2. The culture supernatant from L. chagasi metacyclic promastigotes increases SHP-1 protein abundance and potently inhibits NFAT5 transcriptional activity in mIMCD3 cells. However, L. chagasi in our animal model has no significant effect on urinary concentration. We conclude that L. chagasi, most likely through its secreted virulence factors, activates SHP-1 and reduces NFAT5/TonEBP gene expression, which leads to reduced NFAT5/TonEBP transcriptional activity in the kidney inner medulla. PMID:24990897

  5. Reducible poly(2-dimethylaminoethyl methacrylate): synthesis, cytotoxicity, and gene delivery activity.

    PubMed

    You, Ye-Zi; Manickam, Devika Soundara; Zhou, Qing-Hui; Oupický, David

    2007-10-01

    Reducible polycations represent promising carriers of therapeutic nucleic acids. Oligomers of 2-dimethylaminoethyl methacrylate (DMAEMA) containing terminal thiol groups were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using difunctional chain transfer agent. Reducible poly(DMAEMA) (rPDMAEMA) was synthesized by oxidation of the terminal thiol groups, forming a polymer with disulfide bonds in the backbone. Physico-chemical properties of DNA polyplexes of rPDMAEMA were evaluated by dynamic and static light scattering methods, revealing lower structural density and DNA content than control PDMAEMA polyplexes. Cytotoxicity and transfection activity of rPDMAEMA-based DNA polyplexes were evaluated in vitro. In comparison with control PDMAEMA, only minimum toxic effects of rPDMAEMA were observed in a panel of cell lines. Transfection activity was tested in B16F10 mouse melanoma and six human pancreatic cancer cell lines. rPDMAEMA polyplexes showed a comparable or better activity than control PDMAEMA polyplexes. PMID:17574292

  6. Reducible poly(2-dimethylaminoethyl methacrylate): Synthesis, cytotoxicity, and gene delivery activity

    PubMed Central

    Zhou, Qing-Hui; Oupický, David

    2007-01-01

    Reducible polycations represent promising carriers of therapeutic nucleic acids. Oligomers of 2-dimethylaminoethyl methacrylate (DMAEMA) containing terminal thiol groups were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using difunctional chain transfer agent. Reducible poly(DMAEMA) (rPDMAEMA) was synthesized by oxidation of the terminal thiol groups, forming a polymer with disulfide bonds in the backbone. Physico-chemical properties of DNA polyplexes of rPDMAEMA were evaluated by dynamic and light scattering methods, revealing lower structural density and DNA content than control PDMAEMA polyplexes. Cytotoxicity and transfection activity of rPDMAEMA-based DNA polyplexes were evaluated in vitro. In comparison with control PDMAEMA, only minimum toxic effects of rPDMAEMA were observed in a panel of cell lines. Transfection activity was tested in B16F10 mouse melanoma and six human pancreatic cancer cell lines. rPDMAEMA polyplexes showed a comparable or better activity than control PDMAEMA polyplexes. PMID:17574292

  7. History of falls in Parkinson disease is associated with reduced cholinergic activity

    PubMed Central

    Bohnen, N I.; Müller, M L.T.M.; Koeppe, R A.; Studenski, S A.; Kilbourn, M A.; Frey, K A.; Albin, R L.

    2009-01-01

    Objective: To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD). Background: There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system–mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function. Methods: In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I–III) without dementia and 15 control subjects underwent a clinical assessment and [11C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [11C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging. Results: Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (−12.3%) followed by the PD nonfallers (−6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (−11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers. Conclusions: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD. GLOSSARY AChE = acetylcholinesterase; ANCOVA = analysis of covariance; MMSE = Mini-Mental State Examination; PD

  8. Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD.

    PubMed

    Hayes, Jasmeet Pannu; LaBar, Kevin S; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Dolcos, Florin; Morey, Rajendra A

    2011-05-01

    Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder. PMID:21047644

  9. Sequential activation of multiple grounding pads reduces skin heating during radiofrequency tumor ablation

    PubMed Central

    HAEMMERICH, DIETER; SCHUTT, DAVID JAMES

    2009-01-01

    Purpose Radiofrequency (RF) tumor ablation has become an accepted treatment modality for tumors not amenable to surgery. Skin burns due to ground pad heating may become a limiting factor for further increase in ablation zone dimensions and generator power. We investigated a method were groups of ground pads are sequentially activated to reduce skin heating. Methods We compared conventional operation (i.e. simultaneous connection of all pads) to sequentially switched activation of the pads where different pad combinations are active for periods of ∼0.3 − 8 s. The timing during sequential activation was adjusted to keep the leading edge temperature equal between the pads. We created Finite Element Method computer models of three pads (5 × 5 cm, 1 cm apart) placed in line with the RF electrode on a human thigh to determine differences in tissue heating during simultaneous and sequential ground pad activation. We performed experiments with three ground pads (5 × 10 cm, 4 cm apart) placed on a tissue phantom (1.5 A, 12 min) and measured pad surface and leading edge temperatures. Results Temperature rise below the leading edge for proximal, middle and distal ground pad in relation to active electrode location was 5.9°C ± 0.1°C, 0.8°C ± 0.1°C and 0.3°C ± 0.1°C for conventional operation, and 3.3°C ± 0.1°C, 3.4°C ± 0.2°C and 3.4°C ± 0.2°C for sequentially activated operation in the experiments (p < 0.001). Conclusion Sequential activation of multiple ground pads resulted in reduced maximum tissue temperature. This may reduce the incidence of ground pad burns and may allow higher power RF generators. PMID:18038286

  10. Evaluation of Green Dot: an active bystander intervention to reduce sexual violence on college campuses.

    PubMed

    Coker, Ann L; Cook-Craig, Patricia G; Williams, Corrine M; Fisher, Bonnie S; Clear, Emily R; Garcia, Lisandra S; Hegge, Lea M

    2011-06-01

    Using a cross-sectional survey of a random sample of 7,945 college undergraduates, we report on the association between having received Green Dot active bystander behavior training and the frequency of actual and observed self-reported active bystander behaviors as well as violence acceptance norms. Of 2,504 students aged 18 to 26 who completed the survey, 46% had heard a Green Dot speech on campus, and 14% had received active bystander training during the past 2 years. Trained students had significantly lower rape myth acceptance scores than did students with no training. Trained students also reported engaging in significantly more bystander behaviors and observing more self-reported active bystander behaviors when compared with nontrained students. When comparing self-reported active bystander behavior scores of students trained with students hearing a Green Dot speech alone, the training was associated with significantly higher active bystander behavior scores. Those receiving bystander training appeared to report more active bystander behaviors than those simply hearing a Green Dot speech, and both intervention groups reported more observed and active bystander behaviors than nonexposed students. PMID:21642269

  11. Thermally Reduced Graphene Oxide Electrochemically Activated by Bis-Spiro Quaternary Alkyl Ammonium for Capacitors.

    PubMed

    He, Tieshi; Meng, Xiangling; Nie, Junping; Tong, Yujin; Cai, Kedi

    2016-06-01

    Thermally reduced graphene oxide (RGO) electrochemically activated by a quaternary alkyl ammonium-based organic electrolytes/activated carbon (AC) electrode asymmetric capacitor is proposed. The electrochemical activation process includes adsorption of anions into the pores of AC in the positive electrode and the interlayer intercalation of cations into RGO in the negative electrode under high potential (4.0 V). The EA process of RGO by quaternary alkyl ammonium was investigated by X-ray diffraction and electrochemical measurements, and the effects of cation size and structure were extensively evaluated. Intercalation by quaternary alkyl ammonium demonstrates a small degree of expansion of the whole crystal lattice (d002) and a large degree of expansion of the partial crystal lattice (d002) of RGO. RGO electrochemically activated by bis-spiro quaternary alkyl ammonium in propylene carbonate/AC asymmetric capacitor exhibits good activated efficiency, high specific capacity, and stable cyclability. PMID:27180820

  12. Bai-Hu-Jia-Ren-Shen-Tang Decoction Reduces Fatty Liver by Activating AMP-Activated Protein Kinase In Vitro and In Vivo

    PubMed Central

    Liu, Hui-Kang; Hung, Tzu-Min; Huang, Hsiu-Chen; Lee, I-Jung; Chang, Chia-Chuan; Cheng, Jing-Jy; Lin, Lie-Chwen; Huang, Cheng

    2015-01-01

    Obesity and associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. In Asian traditional medicine, Bai-Hu-Jia-Ren-Shen-Tang (BHJRST) is widely used in diabetes patients to reduce thirst. However, whether it has a therapeutic effect on T2DM or NAFLD is not known. The aim of this study was to examine whether BHJRST had a lipid-lowering effect using a HuS-E/2 cell model of fatty liver induced by palmitate and in a db/db mouse model of dyslipidemia. Incubation of HuS-E/2 cells with palmitate markedly increased lipid accumulation and expression of adipose triglyceride lipase (ATGL), which is involved in lipolysis. BHJRST significantly decreased lipid accumulation and increased ATGL levels and phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream target, acetyl-CoA carboxylase (ACC), which are involved in fatty acid oxidation. Furthermore, after twice daily oral administration for six weeks, BHJRST significantly reduced hepatic fat accumulation in db/db mice, as demonstrated by increased hepatic AMPK and ACC phosphorylation, reduced serum triglyceride levels, and reduced hepatic total lipid content. The results show that BHJRST has a lipid-lowering effect in the liver that is mediated by activation of the AMPK signaling pathway. PMID:26508982

  13. Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves

    PubMed Central

    Bhadoo, Divya; Bajpai, M.; Abid, Ali; Sukanya, Gayan; Agarwala, Sandeep; Srinivas, M.; Deka, Deepika; Agarwal, Nutan; Agarwal, Ramesh; Kumar, Rakesh

    2015-01-01

    Aims: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. Materials and Methods: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV) and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA) values, vesico-ureteric reflux (VUR), renal scars, and glomerular filtration rate (GFR). Results: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m2 body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001) in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. Conclusions: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV. PMID:25829668

  14. Neural correlates of reduced awareness in instrumental activities of daily living in frontotemporal dementia.

    PubMed

    Amanzio, Martina; D'Agata, Federico; Palermo, Sara; Rubino, Elisa; Zucca, Milena; Galati, Antonello; Pinessi, Lorenzo; Castellano, Giancarlo; Rainero, Innocenzo

    2016-10-01

    A decline in instrumental activities of daily living has been described as the earliest functional deficit in patients with neurodegenerative disease. It embraces specific competencies such as: "recalling the date and telephone calls, orienting to new places, remembering the location of objects at home, understanding conversation and the plot of a movie, keeping belongings in order, doing mental calculations and handling money, remembering appointments and shopping lists and performing clerical work". Since changes in instrumental daily living activities are one of the descriptors of behavioural-variant frontotemporal dementia, we decided to investigate the neural correlates of a reduced awareness in this specific domain in twenty-three consecutive behavioural-variant frontotemporal dementia patients. Gray matter volume changes associated with a reduced awareness for the instrumental domain, assessed using a validated caregiver-patient discrepancy questionnaire, were examined. Interestingly, we found disabilities in instrumental daily living activities and a reduced awareness of these to be related to medial prefrontal cortex atrophy, where the mid-cingulate cortices, dorsal anterior insula and cuneous play an important role. Importantly, if the executive system does not function correctly, the comparator mechanism of action self-monitoring does not detect mismatches between the current and previous performance states stored in the personal database, and produces a reduced awareness for the instrumental domain. PMID:27534380

  15. Water in the hydration shell of halide ions has significantly reduced Fermi resonance and moderately enhanced Raman cross section in the OH stretch regions.

    PubMed

    Ahmed, Mohammed; Singh, Ajay K; Mondal, Jahur A; Sarkar, Sisir K

    2013-08-22

    Water in the presence of electrolytes plays an important role in biological and industrial processes. The properties of water, such as the intermolecular coupling, Fermi resonance (FR), hydrogen-bonding, and Raman cross section were investigated by measuring the Raman spectra in the OD and OH stretch regions in presence of alkali halides (NaX; X = F, Cl, Br, I). It is observed that the changes in spectral characteristics by the addition of NaX in D2O are similar to those obtained by the addition of H2O in D2O. The spectral width decreases significantly by the addition of NaX in D2O (H2O) than that in the isotopically diluted water. Quantitative estimation, on the basis of integrated Raman intensity, revealed that the relative Raman cross section, σ(H)/σ(b) (σ(H) and σ(b) are the average Raman cross section of water in the first hydration shell of X(-) and in bulk, respectively), in D2O and H2O is higher than those in the respective isotopically diluted water. These results suggest that water in the hydration shell has reduced FR and intermolecular coupling compared to those in bulk. In the isotopically diluted water, the relative Raman cross section increases with increase in size of the halide ions (σ(H)/σ(b) = 0.6, 1.1, 1.5, and 1.9 for F(-), Cl(-), Br(-), and I(-), respectively), which is assignable to the enhancement of Raman cross section by charge transfer from halide ions to the hydrating water. Nevertheless, the experimentally determined σ(H)/σ(b) is lower than the calculated values obtained on the basis of the energy of the charge transfer state of water. The weak enhancement of σ(H)/σ(b) signifies that the charge transfer transition in the hydration shell of halide ions causes little change in the OD (OH) bond lengths of hydrating water. PMID:23895453

  16. Green synthesis of biphasic TiO₂-reduced graphene oxide nanocomposites with highly enhanced photocatalytic activity.

    PubMed

    Sher Shah, Md Selim Arif; Park, A Reum; Zhang, Kan; Park, Jong Hyeok; Yoo, Pil J

    2012-08-01

    A series of TiO(2)-reduced graphene oxide (RGO) nanocomposites were prepared by simple one-step hydrothermal reactions using the titania precursor, TiCl(4) and graphene oxide (GO) without reducing agents. Hydrolysis of TiCl(4) and mild reduction of GO were simultaneously carried out under hydrothermal conditions. While conventional approaches mostly utilize multistep chemical methods wherein strong reducing agents, such as hydrazine, hydroquinone, and sodium borohydride are employed, our method provides the notable advantages of a single step reaction without employing toxic solvents or reducing agents, thereby providing a novel green synthetic route to produce the nanocomposites of RGO and TiO(2). The as-synthesized nanocomposites were characterized by several crystallographic, microscopic, and spectroscopic characterization methods, which enabled confrimation of the robustness of the suggested reaction scheme. Notably, X-ray diffraction and transmission electron micrograph proved that TiO(2) contained both anatase and rutile phases. In addition, the photocatalytic activities of the synthesized composites were measured for the degradation of rhodamine B dye. The catalyst also can degrade a colorless dye such as benzoic acid under visible light. The synthesized nanocomposites of biphasic TiO(2) with RGO showed enhanced catalytic activity compared to conventional TiO(2) photocatalyst, P25. The photocatalytic activity is strongly affected by the concentration of RGO in the nanocomposites, with the best photocatalytic activity observed for the composite of 2.0 wt % RGO. Since the synthesized biphasic TiO(2)-RGO nanocomposites have been shown to effectively reduce the electron-hole recombination rate, it is anticipated that they will be utilized as anode materials in lithium ion batteries. PMID:22788800

  17. Can a prescribed turnout conditioning program reduce the differential between passive and active turnout in pre-professional dancers?

    PubMed

    Sherman, Astrid J; Mayall, Erika; Tasker, Susan L

    2014-01-01

    Preliminary and speculative findings are reported on the benefits of a prescribed turnout conditioning program (TCP) designed to facilitate pre-professional dancers' active use of natural turnout potential. While of some debate, it is reported in the literature that many dancers use less turnout than what is available to them when measured passively. Key muscles required to achieve full turnout were the focus of the TCP, and exercises were introduced in a manner that, theoretically, should stimulate appropriate activation patterns for proper turnout biomechanics. A group of female pre-professional dancers (13 to 17 years old, training 20 to 25 hours a week, N = 16) were measured before and after the 7-week program for total passive turnout, total active turnout, passive hip external rotation, and tibial torsion. Statistically and functionally significant improvements were found in both static total active turnout (standing in first position on a large piece of paper) and dynamic total active turnout (standing in first position on rotational Balanced Body discs). These results indicate that the TCP was effective in improving active turnout, thereby reducing the differential between passive and active turnout in pre-professional ballet dancers. Implications are discussed for dancer-specific turnout conditioning programs, the role of cognitive imagery cueing, and emphasis on the importance of quantity with quality in the conditioning and teaching of active turnout. PMID:25474295

  18. Cdc42 and Rac1 activity is reduced in human pheochromocytoma and correlates with FARP1 and ARHGEF1 expression.

    PubMed

    Croisé, Pauline; Houy, Sébastien; Gand, Mathieu; Lanoix, Joël; Calco, Valérie; Tóth, Petra; Brunaud, Laurent; Lomazzi, Sandra; Paramithiotis, Eustache; Chelsky, Daniel; Ory, Stéphane; Gasman, Stéphane

    2016-04-01

    Among small GTPases from the Rho family, Cdc42, RAC, and Rho are well known to mediate a large variety of cellular processes linked with cancer biology through their ability to cycle between an inactive (GDP-bound) and an active (GTP-bound) state. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP to generate the activated form, whereas the GTPase-activating proteins (GAPs) catalyze GTP hydrolysis, leading to the inactivated form. Modulation of Rho GTPase activity following altered expression of RHO-GEFs and/or RHO-GAPs has already been reported in various human tumors. However, nothing is known about the Rho GTPase activity or the expression of their regulators in human pheochromocytomas, a neuroendocrine tumor (NET) arising from chromaffin cells of the adrenal medulla. In this study, we demonstrate, through an ELISA-based activity assay, that Rac1 and Cdc42 activities decrease in human pheochromocytomas (PCCs) compared with the matched adjacent non-tumor tissue. Furthermore, through quantitative mass spectrometry (MS) approaches, we show that the expression of two RHO-GEF proteins, namely ARHGEF1 and FARP1, is significantly reduced in tumors compared with matched non-tumor tissue, whereas ARHGAP36 expression is increased. Moreover, siRNA-based knockdown of ARHGEF1 and FARP1 in PC12 cells leads to a significant inhibition of Rac1 and Cdc42 activities, respectively. Finally, a principal component analysis (PCA) of our dataset was able to discriminate PCC from non-tumor tissue and indicates a close correlation between Cdc42/Rac1 activity and FARP1/ARHGEF1 expression. Altogether, our findings reveal for the first time the importance of modulation of Rho GTPase activities and expression of their regulators in human PCCs. PMID:26911374

  19. Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

    PubMed Central

    Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

    2014-01-01

    Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

  20. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS

    PubMed Central

    Cofiell, Roxanne; Kukreja, Anjli; Bedard, Krystin; Yan, Yan; Mickle, Angela P.; Ogawa, Masayo; Bedrosian, Camille L.

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening disease characterized by uncontrolled complement activation, systemic thrombotic microangiopathy (TMA), and vital organ damage. We evaluated the effect of terminal complement blockade with the anti-C5 monoclonal antibody eculizumab on biomarkers of cellular processes involved in TMA in patients with aHUS longitudinally, during up to 1 year of treatment, compared with in healthy volunteers. Biomarker levels were elevated at baseline in most patients, regardless of mutational status, plasma exchange/infusion use, platelet count, or lactate dehydrogenase or haptoglobin levels. Eculizumab reduced terminal complement activation (C5a and sC5b-9) and renal injury markers (clusterin, cystatin-C, β2-microglobulin, and liver fatty acid binding protein-1) to healthy volunteer levels and reduced inflammation (soluble tumor necrosis factor receptor-1), coagulation (prothrombin fragment F1+2 and d-dimer), and endothelial damage (thrombomodulin) markers to near-normal levels. Alternative pathway activation (Ba) and endothelial activation markers (soluble vascular cell adhesion molecule-1) decreased but remained elevated, reflecting ongoing complement activation in aHUS despite complete terminal complement blockade. These results highlight links between terminal complement activation and inflammation, endothelial damage, thrombosis, and renal injury and underscore ongoing risk for systemic TMA and progression to organ damage. Further research regarding underlying complement dysregulation is warranted. This trial was registered at www.clinicaltrials.gov as #NCT01194973. PMID:25833956

  1. Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep.

    PubMed

    Deng, Shoulong; Yu, Kun; Wu, Qian; Li, Yan; Zhang, Xiaosheng; Zhang, Baolu; Liu, Guoshi; Liu, Yixun; Lian, Zhengxing

    2016-01-01

    Toll-like receptor 4 (TLR4) is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune system. Increased activation of TLR4 can lead to the induction of oxidative stress. Herein, the pathway whereby TLR4 affects antioxidant activity was studied. In TLR4-overexpressing sheep, TLR4 expression was found to be related to the integration copy number when monocytes were challenged with lipopolysaccharide (LPS). Consequently, production of malondialdehyde (MDA) was increased, which could increase the activation of prooxidative stress enzymes. Meanwhile, activation of an antioxidative enzyme, glutathione peroxidase (GSH-Px), was increased. Real-time PCR showed that expression of activating protein-1 (AP-1) and the antioxidative-related genes was increased. By contrast, the expression levels of superoxide dismutase 1 (SOD1) and catalase (CAT) were reduced. In transgenic sheep, glutathione (GSH) levels were dramatically reduced. Furthermore, transgenic sheep were intradermally injected with LPS in each ear. The amounts of inflammatory infiltrates were correlated with the number of TLR4 copies that were integrated in the genome. Additionally, the translation of γ-glutamylcysteine synthetase (γ-GCS) was increased. Our findings indicated that overexpression of TLR4 in sheep could ameliorate oxidative injury through GSH secretion that was induced by LPS stimulation. Furthermore, TLR4 promoted γ-GCS translation through the AP-1 pathway, which was essential for GSH synthesis. PMID:26640618

  2. Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep

    PubMed Central

    Deng, Shoulong; Yu, Kun; Wu, Qian; Li, Yan; Zhang, Xiaosheng; Zhang, Baolu; Liu, Guoshi; Liu, Yixun; Lian, Zhengxing

    2016-01-01

    Toll-like receptor 4 (TLR4) is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune system. Increased activation of TLR4 can lead to the induction of oxidative stress. Herein, the pathway whereby TLR4 affects antioxidant activity was studied. In TLR4-overexpressing sheep, TLR4 expression was found to be related to the integration copy number when monocytes were challenged with lipopolysaccharide (LPS). Consequently, production of malondialdehyde (MDA) was increased, which could increase the activation of prooxidative stress enzymes. Meanwhile, activation of an antioxidative enzyme, glutathione peroxidase (GSH-Px), was increased. Real-time PCR showed that expression of activating protein-1 (AP-1) and the antioxidative-related genes was increased. By contrast, the expression levels of superoxide dismutase 1 (SOD1) and catalase (CAT) were reduced. In transgenic sheep, glutathione (GSH) levels were dramatically reduced. Furthermore, transgenic sheep were intradermally injected with LPS in each ear. The amounts of inflammatory infiltrates were correlated with the number of TLR4 copies that were integrated in the genome. Additionally, the translation of γ-glutamylcysteine synthetase (γ-GCS) was increased. Our findings indicated that overexpression of TLR4 in sheep could ameliorate oxidative injury through GSH secretion that was induced by LPS stimulation. Furthermore, TLR4 promoted γ-GCS translation through the AP-1 pathway, which was essential for GSH synthesis. PMID:26640618

  3. Heat-treatment effect on impact properties of reduced-activation steels*1

    NASA Astrophysics Data System (ADS)

    Klueh, R. L.; Maziasz, P. J.; Alexander, D. J.

    1991-03-01

    The effect of heat treatment on the impact behavior of eight experimental heats of reduced-activation ferritic steels was investigated. Steels with 2 {1}/{4}, 5, 9, and 12 wt% Cr and containing tungsten, vanadium, and tantalum were examined. Impact properties of steels with 2 {1}/{4} wt% Cr depended on microstructure, which was affected by cooling rate after austenitization. By heat-treating the 2 {1}/{4} wt% Cr steels to change the microstructure from a bainitic structure containing ferrite to one without ferrite, the ductile-brittle transition temperatures were reduced substantially. The cooling rate had essentially no effect on the high-chromium martensitic steels.

  4. Young, Healthy Subjects Can Reduce the Activity of Calf Muscles When Provided with EMG Biofeedback in Upright Stance.

    PubMed

    Vieira, Taian M; Baudry, Stéphane; Botter, Alberto

    2016-01-01

    Recent evidence suggests the minimization of muscular effort rather than of the size of bodily sway may be the primary, nervous system goal when regulating the human, standing posture. Different programs have been proposed for balance training; none however has been focused on the activation of postural muscles during standing. In this study we investigated the possibility of minimizing the activation of the calf muscles during standing through biofeedback. By providing subjects with an audio signal that varied in amplitude and frequency with the amplitude of surface electromyograms (EMG) recorded from different regions of the gastrocnemius and soleus muscles, we expected them to be able to minimize the level of muscle activation during standing without increasing the excursion of the center of pressure (CoP). CoP data and surface EMG from gastrocnemii, soleus and tibialis anterior muscles were obtained from 10 healthy participants while standing at ease and while standing with EMG biofeedback. Four sensitivities were used to test subjects' responsiveness to the EMG biofeedback. Compared with standing at ease, the two most sensitive feedback conditions induced a decrease in plantar flexor activity (~15%; P < 0.05) and an increase in tibialis anterior EMG (~10%; P < 0.05). Furthermore, CoP mean position significantly shifted backward (~30 mm). In contrast, the use of less sensitive EMG biofeedback resulted in a significant decrease in EMG activity of ankle plantar flexors with a marginal increase in TA activity compared with standing at ease. These changes were not accompanied by greater CoP displacements or significant changes in mean CoP position. Key results revealed subjects were able to keep standing stability while reducing the activity of gastrocnemius and soleus without loading their tibialis anterior muscle when standing with EMG biofeedback. These results may therefore posit the basis for the development of training protocols aimed at assisting subjects in

  5. Young, Healthy Subjects Can Reduce the Activity of Calf Muscles When Provided with EMG Biofeedback in Upright Stance

    PubMed Central

    Vieira, Taian M.; Baudry, Stéphane; Botter, Alberto

    2016-01-01

    Recent evidence suggests the minimization of muscular effort rather than of the size of bodily sway may be the primary, nervous system goal when regulating the human, standing posture. Different programs have been proposed for balance training; none however has been focused on the activation of postural muscles during standing. In this study we investigated the possibility of minimizing the activation of the calf muscles during standing through biofeedback. By providing subjects with an audio signal that varied in amplitude and frequency with the amplitude of surface electromyograms (EMG) recorded from different regions of the gastrocnemius and soleus muscles, we expected them to be able to minimize the level of muscle activation during standing without increasing the excursion of the center of pressure (CoP). CoP data and surface EMG from gastrocnemii, soleus and tibialis anterior muscles were obtained from 10 healthy participants while standing at ease and while standing with EMG biofeedback. Four sensitivities were used to test subjects' responsiveness to the EMG biofeedback. Compared with standing at ease, the two most sensitive feedback conditions induced a decrease in plantar flexor activity (~15%; P < 0.05) and an increase in tibialis anterior EMG (~10%; P < 0.05). Furthermore, CoP mean position significantly shifted backward (~30 mm). In contrast, the use of less sensitive EMG biofeedback resulted in a significant decrease in EMG activity of ankle plantar flexors with a marginal increase in TA activity compared with standing at ease. These changes were not accompanied by greater CoP displacements or significant changes in mean CoP position. Key results revealed subjects were able to keep standing stability while reducing the activity of gastrocnemius and soleus without loading their tibialis anterior muscle when standing with EMG biofeedback. These results may therefore posit the basis for the development of training protocols aimed at assisting subjects in

  6. Risk of significant cytopenias after treatment with tocilizumab in systemic juvenile arthritis patients with a history of macrophage activation syndrome

    PubMed Central

    2012-01-01

    Tocilizumab (TCZ) is the first FDA- approved treatment for systemic juvenile idiopathic arthritis (sJIA). We report 3 cases of cytopenias in children with sJIA treated with TCZ. Two of the children who developed significant cytopenias shortly after initiation of TCZ had a history of macrophage activation syndrome. We raise the possibility that patients with a tendency towards MAS have an increased risk of developing cytopenias when treated with tocilizumab. PMID:22931129

  7. AMP-activated Protein Kinase Suppresses Biosynthesis of Glucosylceramide by Reducing Intracellular Sugar Nucleotides*

    PubMed Central

    Ishibashi, Yohei; Hirabayashi, Yoshio

    2015-01-01

    The membrane glycolipid glucosylceramide (GlcCer) plays a critical role in cellular homeostasis. Its intracellular levels are thought to be tightly regulated. How cells regulate GlcCer levels remains to be clarified. AMP-activated protein kinase (AMPK), which is a crucial cellular energy sensor, regulates glucose and lipid metabolism to maintain energy homeostasis. Here, we investigated whether AMPK affects GlcCer metabolism. AMPK activators (5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside and metformin) decreased intracellular GlcCer levels and synthase activity in mouse fibroblasts. AMPK inhibitors or AMPK siRNA reversed these effects, suggesting that GlcCer synthesis is negatively regulated by an AMPK-dependent mechanism. Although AMPK did not affect the phosphorylation or expression of GlcCer synthase, the amount of UDP-glucose, an activated form of glucose required for GlcCer synthesis, decreased under AMPK-activating conditions. Importantly, the UDP-glucose pyrophosphatase Nudt14, which degrades UDP-glucose, generating UMP and glucose 1-phosphate, was phosphorylated and activated by AMPK. On the other hand, suppression of Nudt14 by siRNA had little effect on UDP-glucose levels, indicating that mammalian cells have an alternative UDP-glucose pyrophosphatase that mainly contributes to the reduction of UDP-glucose under AMPK-activating conditions. Because AMPK activators are capable of reducing GlcCer levels in cells from Gaucher disease patients, our findings suggest that reducing GlcCer through AMPK activation may lead to a new strategy for treating diseases caused by abnormal accumulation of GlcCer. PMID:26048992

  8. Lysosomal Acid Lipase Activity Is Reduced Both in Cryptogenic Cirrhosis and in Cirrhosis of Known Etiology

    PubMed Central

    Vespasiani-Gentilucci, Umberto; Gallo, Paolo; Piemonte, Fiorella; Riva, Elisabetta; Porcari, Aldostefano; Vorini, Ferruccio; Tozzi, Giulia; Piccioni, Livia; Galati, Giovanni; De Vincentis, Antonio; Carotti, Simone; Morini, Sergio; D’Amico, Jessica; Angeletti, Silvia; Pedone, Claudio; Picardi, Antonio

    2016-01-01

    Lysosomal acid lipase deficiency (LAL-d) is a rare autosomal recessive disease in which LAL activity is almost absent, with consequent massive microvesicular steatosis evolving to cirrhosis and liver failure. We aimed to determine LAL-activity, and to investigate the most common single nucleotide polymorphism (SNP) affecting the LIPA gene and responsible for 50–70% of LAL-d cases (rs116928232 c.894G>A), in patients with cryptogenic cirrhosis. Sixty-three patients with cryptogenic cirrhosis, 88 cirrhotics of known etiology, and 97 healthy subjects were enrolled. LAL-activity was determined in dried-blood-spot (DBS). The c.894G>A mutation was analyzed by pyrosequencing method in SNP mode. LAL-activity was severely reduced in patients with cryptogenic cirrhosis with respect to healthy subjects [0.62 (0.44–0.86) Vs 0.96 (0.75–1.25) nmol/spot/h, p<0.001)], but it was also reduced in known-etiology cirrhotics [0.54 (0.42–0.79) nmol/spot/h, p<0.001 Vs healthy subjects; p = 0.5 Vs cryptogenic cirrhotics]. Fourteen percent of cryptogenic cirrhotics and 20% of known-etiology cirrhotics showed a LAL-activity in the range of heterozygous carriers of LIPA gene mutations (0.15–0.40 nmol/spot/h). However, none of the subjects with reduced LAL-activity carried the c.894G>A SNP except for one patient with HCV cirrhosis. By multivariate analysis, LAL-activity was not associated with age, sex, liver enzymes, liver function or lipid parameters, while it was independently associated with white blood cell (β = 0.2; p<0.01) and platelet (β = 0.4; p<0.001) counts and with the condition of cirrhosis (β = -0.2; p = 0.04). Conclusion Liver cirrhosis is characterized by a severe acquired reduction of LAL-activity, the precise causes and consequences of which need to be further addressed. DBS-determined lysosomal enzyme activities seem to be affected by white blood cell and platelet counts, and the specificity of these tests can be reduced when applied to determined populations

  9. Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.

    PubMed

    Yavari, Arash; Stocker, Claire J; Ghaffari, Sahar; Wargent, Edward T; Steeples, Violetta; Czibik, Gabor; Pinter, Katalin; Bellahcene, Mohamed; Woods, Angela; Martínez de Morentin, Pablo B; Cansell, Céline; Lam, Brian Y H; Chuster, André; Petkevicius, Kasparas; Nguyen-Tu, Marie-Sophie; Martinez-Sanchez, Aida; Pullen, Timothy J; Oliver, Peter L; Stockenhuber, Alexander; Nguyen, Chinh; Lazdam, Merzaka; O'Dowd, Jacqueline F; Harikumar, Parvathy; Tóth, Mónika; Beall, Craig; Kyriakou, Theodosios; Parnis, Julia; Sarma, Dhruv; Katritsis, George; Wortmann, Diana D J; Harper, Andrew R; Brown, Laurence A; Willows, Robin; Gandra, Silvia; Poncio, Victor; de Oliveira Figueiredo, Márcio J; Qi, Nathan R; Peirson, Stuart N; McCrimmon, Rory J; Gereben, Balázs; Tretter, László; Fekete, Csaba; Redwood, Charles; Yeo, Giles S H; Heisler, Lora K; Rutter, Guy A; Smith, Mark A; Withers, Dominic J; Carling, David; Sternick, Eduardo B; Arch, Jonathan R S; Cawthorne, Michael A; Watkins, Hugh; Ashrafian, Houman

    2016-05-10

    Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease. PMID:27133129

  10. Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice.

    PubMed

    Qiao, Liping; Guo, Zhuyu; Bosco, Chris; Guidotti, Stefano; Wang, Yunfeng; Wang, Mingyong; Parast, Mana; Schaack, Jerome; Hay, William W; Moore, Thomas R; Shao, Jianhua

    2015-09-01

    This study investigated how maternal overnutrition and obesity regulate expression and activation of proteins that facilitate lipid transport in the placenta. To create a maternal overnutrition and obesity model, primiparous C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF-fed dams had significantly increased serum levels of free fatty acid and body fat. Despite no significant difference in placental weight, lipoprotein lipase (LPL) protein levels and activity were remarkably elevated in placentas from HF-fed dams. Increased triglyceride content and mRNA levels of CD36, VLDLr, FABP3, FABPpm, and GPAT2 and -3 were also found in placentas from HF-fed dams. Although both peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α protein levels were significantly increased in placentas of the HF group, only PPARγ exhibited a stimulative effect on LPL expression in cultured JEG-3 human trophoblasts. Maternal HF feeding remarkably decreased SIRT1 expression in placentas. Through use of an SIRT1 activator and inhibitor and cultured trophoblasts, an inhibitory effect of SIRT1 on LPL expression was demonstrated. We also found that SIRT1 suppresses PPARγ expression in trophoblasts. Most importantly, inhibition of PPARγ abolished the SIRT1-mediated regulatory effect on LPL expression. Together, these results indicate that maternal overnutrition induces LPL expression in trophoblasts by reducing the inhibitory effect of SIRT1 on PPARγ. PMID:25948680

  11. Integrating the public in mosquito management: active education by community peers can lead to significant reduction in peridomestic container mosquito habitats.

    PubMed

    Healy, Kristen; Hamilton, George; Crepeau, Taryn; Healy, Sean; Unlu, Isik; Farajollahi, Ary; Fonseca, Dina M

    2014-01-01

    Mosquito species that utilize peridomestic containers for immature development are commonly aggressive human biters, and because they often reach high abundance, create significant nuisance. One of these species, the Asian tiger mosquito Aedes albopictus, is an important vector of emerging infectious diseases, such as dengue, chikungunya, and Zika fevers. Integrated mosquito management (IMM) of Ae. albopictus is particularly difficult because it requires access to private yards in urban and suburban residences. It has become apparent that in the event of a public health concern due to this species, homeowners will have to be active participants in the control process by reducing mosquito habitats in their properties, an activity known as source reduction. However, limited attempts at quantifying the effect of source reduction by homeowners have had mixed results. Of note, many mosquito control programs in the US have some form of education outreach, however the primary approach is often passive focusing on the distribution of education materials as flyers. In 2010, we evaluated the use of active community peer education in a source reduction program, using AmeriCorps volunteers. The volunteers were mobilized over a 4-week period, in two areas with approximately 1,000 residences each in urban Mercer and suburban Monmouth counties in New Jersey, USA. The volunteers were first provided training on peridomestic mosquitoes and on basic approaches to reducing the number of container habitats for mosquito larvae in backyards. Within the two treatment areas the volunteers successfully engaged 758 separate homes. Repeated measures analysis of variance showed a significant reduction in container habitats in the sites where the volunteers actively engaged the community compared to untreated control areas in both counties. Our results suggest that active education using community peer educators can be an effective means of source reduction, and a critical tool in the arsenal

  12. Integrating the Public in Mosquito Management: Active Education by Community Peers Can Lead to Significant Reduction in Peridomestic Container Mosquito Habitats

    PubMed Central

    Healy, Kristen; Hamilton, George; Crepeau, Taryn; Healy, Sean; Unlu, Isik; Farajollahi, Ary; Fonseca, Dina M.

    2014-01-01

    Mosquito species that utilize peridomestic containers for immature development are commonly aggressive human biters, and because they often reach high abundance, create significant nuisance. One of these species, the Asian tiger mosquito Aedes albopictus, is an important vector of emerging infectious diseases, such as dengue, chikungunya, and Zika fevers. Integrated mosquito management (IMM) of Ae. albopictus is particularly difficult because it requires access to private yards in urban and suburban residences. It has become apparent that in the event of a public health concern due to this species, homeowners will have to be active participants in the control process by reducing mosquito habitats in their properties, an activity known as source reduction. However, limited attempts at quantifying the effect of source reduction by homeowners have had mixed results. Of note, many mosquito control programs in the US have some form of education outreach, however the primary approach is often passive focusing on the distribution of education materials as flyers. In 2010, we evaluated the use of active community peer education in a source reduction program, using AmeriCorps volunteers. The volunteers were mobilized over a 4-week period, in two areas with approximately 1,000 residences each in urban Mercer and suburban Monmouth counties in New Jersey, USA. The volunteers were first provided training on peridomestic mosquitoes and on basic approaches to reducing the number of container habitats for mosquito larvae in backyards. Within the two treatment areas the volunteers successfully engaged 758 separate homes. Repeated measures analysis of variance showed a significant reduction in container habitats in the sites where the volunteers actively engaged the community compared to untreated control areas in both counties. Our results suggest that active education using community peer educators can be an effective means of source reduction, and a critical tool in the arsenal

  13. Application of Feedforward Adaptive Active-Noise Control for Reducing Blade Passing Noise in Centrifugal Fans

    NASA Astrophysics Data System (ADS)

    WU, J.-D.; BAI, M. R.

    2001-02-01

    This paper describes two configurations of feedforward adaptive active-noise control (ANC) technique for reducing blade passing noise in centrifugal fans. In one configuration, the control speaker is installed at the cut-off region of the fan, while in the other configuration at the exit duct. The proposed ANC system is based on the filtered-x least-mean-squares (FXLMS) algorithm with multi-sine synthesized reference signal and frequency counting and is implemented by using a digital signal processor (DSP). Experiments are carried out to evaluate the proposed system for reducing the noise at the blade passing frequency (BPF) and its harmonics at various flow speeds. The results of the experiment indicated that the ANC technique is effective in reducing the blade passing noise for two configurations by using the feedforward adaptive control.

  14. Synovial sarcoma cell lines showed reduced DNA repair activity and sensitivity to a PARP inhibitor.

    PubMed

    Yamasaki, Hiroyuki; Miyamoto, Mamiko; Yamamoto, Yuki; Kondo, Tadashi; Watanabe, Toshiki; Ohta, Tsutomu

    2016-08-01

    Synovial sarcoma is a soft-tissue sarcoma and a rare type of cancer. Unfortunately, effective chemotherapies for synovial sarcomas have not been established. In this report, we show that synovial sarcoma cell lines have reduced repair activity for DNA damage induced by ionizing radiation (IR) and a topoisomerase II inhibitor (etoposide). We also observed reduced recruitment of RAD51 homologue (S. cerevisiae; RAD51) at sites of double-strand breaks (DSBs) in synovial sarcoma cell lines that had been exposed to IR. These findings showed that synovial sarcoma cell lines are defective in homologous recombination (HR) repair. Furthermore, we found that a poly-(ADP-ribose) polymerase (PARP) inhibitor (AZD2281; olaparib) effectively reduced the growth of synovial sarcoma cell lines in the presence of an alkylating agent (temozolomide). Our findings offer evidence that treatment combining a PARP inhibitor and an alkylating agent could have therapeutic benefits in the treatment of synovial sarcoma. PMID:27353471

  15. HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation

    PubMed Central

    Henrick, Bethany M.; Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2015-01-01

    Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2) physically inhibited HIV-induced NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs) for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2). Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41, act as viral PAMPs signaling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development. PMID:26347747

  16. Reduced cytochrome oxidase activity in the retrosplenial cortex after lesions to the anterior thalamic nuclei.

    PubMed

    Mendez-Lopez, Magdalena; Arias, Jorge L; Bontempi, Bruno; Wolff, Mathieu

    2013-08-01

    The anterior thalamic nuclei (ATN) make a critical contribution to hippocampal system functions. Growing experimental work shows that the effects of ATN lesions often resemble those of hippocampal lesions and both markedly reduce the expression of immediate-early gene markers in the retrosplenial cortex, which still appears normal by standard histological means. This study shows that moderate ATN damage was sufficient to produce severe spatial memory impairment as measured in a radial-arm maze. Furthermore, ATN rats exhibited reduced cytochrome oxidase activity in the most superficial cortical layers of the granular retrosplenial cortex, and, to a lesser extent, in the anterior cingulate cortex. By contrast, no change in cytochrome oxidase activity was observed in other limbic cortical regions or in the hippocampal formation. Altogether our results indicate that endogenous long-term brain metabolic capacity within the granular retrosplenial cortex is compromised by even limited ATN damage. PMID:23660649

  17. Activated microglia in acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Fujita, Yuji; Takanashi, Jun-Ichi; Takei, Haruka; Ota, Setsuo; Fujii, Katsunori; Sakuma, Hiroshi; Hayashi, Masaharu

    2016-07-15

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. The exact pathogenesis of and the best therapeutic strategy for AESD are uncertain. We firstly performed a brain biopsy in a 2-year-old boy with AESD associated with RS viral infection, which revealed activated ameoboid microglia accumulation around degenerated neuron, and astrogliosis in the affected cortex. Glutamate released from activated microglia may play an important role in the pathogenesis of AESD, which is compatible with the previous report of magnetic resonance spectroscopy showing elevated glutamate. PMID:27288783

  18. Thermophysical and mechanical properties of Fe-(8-9)%Cr reduced activation steels

    SciTech Connect

    Zinkle, S.J.; Robertson, J.P.; Klueh, R.L.

    1998-09-01

    The key thermophysical and mechanical properties for 8--9%Cr reduced activation ferritic/martensitic steels are summarized, including temperature-dependent tensile properties in the unirradiated and irradiated conditions, stress-rupture behavior, elastic constants, thermal conductivity, thermal expansion, specific heat, and ductile-to-brittle transition temperature. The estimated lower and upper temperatures limits for structural applications are 250 and 550 C due to radiation hardening/embrittlement and thermal creep considerations, respectively.

  19. Overexpression of α-synuclein simultaneously increases glutamate NMDA receptor phosphorylation and reduces glucocerebrosidase activity.

    PubMed

    Yang, Junfeng; Hertz, Ellen; Zhang, Xiaoqun; Leinartaité, Lina; Lundius, Ebba Gregorsson; Li, Jie; Svenningsson, Per

    2016-01-12

    Progressive accumulation of α-synuclein (α-syn)-containing protein aggregates throughout the nervous system is a pathological hallmark of Parkinson's disease (PD). The mechanisms whereby α-syn exerts neurodegeneration remain to be fully understood. Here we show that overexpression of α-syn in transgenic mice leads to increased phosphorylation of glutamate NMDA receptor (NMDAR) subunits NR1 and NR2B in substantia nigra and striatum as well as reduced glucocerebrosidase (GCase) levels. Similarly, molecular studies performed in mouse N2A cells stably overexpressing human α-syn ((α-syn)N2A) showed that phosphorylation states of the same NMDAR subunits were increased, whereas GCase levels and lysosomal GCase activity were reduced. (α-syn)N2A cells showed an increased sensitivity to neurotoxicity towards 6-hydroxydopamine and NMDA. However, wildtype N2A, but not (α-syn)N2A cells, showed a further reduction in viability when co-incubated with 6-hydroxydopamine and the lysosomal inhibitors NH4Cl and leupeptin, suggesting that α-syn per se perturbs lysosomal functions. NMDA treatment reduced lysosomal GCase activity to the same extent in (α-syn)N2A cells as in wildtype N2A cells, indicating that the α-syn-dependent difference in NMDA neurotoxicity is unrelated to an altered GCase activity. Nevertheless, these data provide molecular evidence that overexpression of α-syn simultaneously induces two potential neurotoxic hits by increasing glutamate NMDA receptor phosphorylation, consistent with increased NMDA receptors functionality, and reducing GCase activity. PMID:26610904

  20. Activation of innate immunity to reduce lung metastases in breast cancer.

    PubMed

    Jordan, Julie L; Nowak, A; Lee, T D G

    2010-05-01

    Breast cancer continues to be one of the leading causes of cancer death in women. Mortality is primarily due to the development of metastases. Although therapies exist, they lack efficacy in preventing metastatic growth. As a result, novel agents are being investigated. In particular, treatments that target the immune system are being examined as potential anti-neoplastic agents. Cordyceps sinensis (Cs) is a fungus that has been used for over 2,000 years in China as a treatment for a variety of conditions including neoplasms. The available evidence suggests that efficacy of Cs as an anti-neoplastic therapeutic agent is related to a role as an activator of innate immune responses. The objectives of this study were: to investigate the ability of Cs to activate macrophages to produce factors that will induce protective responses against tumour growth; to study the ability of Cs to reduce primary tumour growth in vivo; and to examine the ability of Cs to reduce lung metastasis growth in vivo. We found that oral Cs does not reduce primary tumour growth but can reduce lung metastasis occurrence in a surgical excision model of metastatic mammary carcinoma. The evidence we have shown to date suggests that the reduction in metastases growth may be due to the effects of macrophage-derived factors on tumour cell cycle. PMID:19956948

  1. Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists.

    PubMed

    Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard; Gurven, Michael

    2016-03-01

    Sedentary lifestyle contributes to osteoporosis and fragility fracture risks among modern humans, but whether such risks are prevalent in physically active preindustrial societies with lower life expectancies is unclear. Osteoporosis should be readily observable in preindustrial societies if it was regularly experienced over human history. In this study of 142 older adult Tsimane forager-horticulturalists (mean age ± SD, 62.1 ± 8.6 years; range, 50 to 85 years; 51% female) we used calcaneal quantitative ultrasonography (qUS) to assess bone status, document prevalence of adults with reduced bone status, and identify factors (demographic, anthropometric, immunological, kinesthetic) associated with reduced bone status. Men (23%) are as likely as women (25%) to have reduced bone status, although age-related decline in qUS parameters is attenuated for men. Adiposity and fat-free mass positively co-vary with qUS parameters for women but not men. Leukocyte count is inversely associated with qUS parameters controlling for potential confounders; leukocyte count is positively correlated within adults over time, and adults with persistently low counts have higher adjusted qUS parameters (6% to 8%) than adults with a high count. Reduced bone status characteristic of osteoporosis is common among active Tsimane with minimal exposure to osteoporosis risk factors found in industrialized societies, but with energetic constraints and high pathogen burden. © 2015 American Society for Bone and Mineral Research. PMID:26460548

  2. Addition of Selenium Nanoparticles to Electrospun Silk Scaffold Improves the Mammalian Cell Activity While Reducing Bacterial Growth

    PubMed Central

    Chung, Stanley; Ercan, Batur; Roy, Amit K.; Webster, Thomas J.

    2016-01-01

    Silk possesses many beneficial wound healing properties, and electrospun scaffolds are especially applicable for skin applications, due to their smaller interstices and higher surface areas. However, purified silk promotes microbial growth. Selenium nanoparticles have shown excellent antibacterial properties and are a novel antimicrobial chemistry. Here, electrospun silk scaffolds were doped with selenium nanoparticles to impart antibacterial properties to the silk scaffolds. Results showed significantly improved bacterial inhibition and mild improvement in human dermal fibroblast metabolic activity. These results suggest that the addition of selenium nanoparticles to electrospun silk is a promising approach to improve wound healing with reduced infection, without relying on antibiotics. PMID:27471473

  3. PGE2 Reduces MMP-14 and Increases Plasminogen Activator Inhibitor-1 in Cardiac Fibroblasts

    PubMed Central

    Kassem, Kamal M.; Clevenger, Margarette H.; Szandzik, David L.; Peterson, Edward; Harding, Pamela

    2014-01-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating towards 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  4. Cerium Oxide Nanoparticles Reduce Microglial Activation and Neurodegenerative Events in Light Damaged Retina

    PubMed Central

    Fiorani, Lavinia; Passacantando, Maurizio; Santucci, Sandro; Di Marco, Stefano; Bisti, Silvia; Maccarone, Rita

    2015-01-01

    The first target of any therapy for retinal neurodegeneration is to slow down the progression of the disease and to maintain visual function. Cerium oxide or ceria nanoparticles reduce oxidative stress, which is known to play a pivotal role in neurodegeneration. Our aim was to investigate whether cerium oxide nanoparticles were able to mitigate neurodegeneration including microglial activation and related inflammatory processes induced by exposure to high intensity light. Cerium oxide nanoparticles were injected intravitreally or intraveinously in albino Sprague-Dawley rats three weeks before exposing them to light damage of 1000 lux for 24 h. Electroretinographic recordings were performed a week after light damage. The progression of retinal degeneration was evaluated by measuring outer nuclear layer thickness and TUNEL staining to quantify photoreceptors death. Immunohistochemical analysis was used to evaluate retinal stress, neuroinflammatory cytokines and microglial activation. Only intravitreally injected ceria nanoparticles were detected at the level of photoreceptor outer segments 3 weeks after the light damage and electoretinographic recordings showed that ceria nanoparticles maintained visual response. Moreover, this treatment reduced neuronal death and “hot spot” extension preserving the outer nuclear layer morphology. It is noteworthy that in this work we demonstrated, for the first time, the ability of ceria nanoparticles to reduce microglial activation and their migration toward outer nuclear layer. All these evidences support ceria nanoparticles as a powerful therapeutic agent in retinal neurodegenerative processes. PMID:26469804

  5. PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts.

    PubMed

    Kassem, Kamal M; Clevenger, Margarette H; Szandzik, David L; Peterson, Edward; Harding, Pamela

    2014-10-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  6. Evaluation on Fatigue Crack Propagation of Reduced Activation Ferritic Steel (JLF-1) at High Temperature

    NASA Astrophysics Data System (ADS)

    Yoon, Han Ki; Kim, Sa Woong; Lee, Sang Pill; Katoh, Yutai; Kohyama, Akira

    Recently, reduced activation ferritic/martensitic steel, vanadium alloy and SiC/SiC composite are embossed for nuclear fusion reactor in accordance with the coolant. Especially, reduced activation ferritic/martensitic steel is very suitable material for nuclear fusion reactor, because it has low coefficient of thermal expansion and excellent heat conductivity. The objective of this study is to investigate fatigue crack propagation behavior in the Reduced Activation Ferritic Steel (JLF-1). The fatigue crack propagation behavior of the JLF-1 steel was investigated by the constant-amplitude loading test for the stress ratios R = 0.1, 0.3 and 0.5 respectively. The fatigue crack growth tests carried out at room temperature and 400°C for base metal and weld metal. The effects of stress ratio, test temperature, specimen size and TIG welding on the fatigue crack propagation behaviors for JLF-1 steel were discussed within the Paris law. Particularly, the fatigue crack propagation rate of a weld metal was similar to that of base metal at the stress ratio of 0.3. Also, the fatigue crack propagation rate of a half size specimen was similar to that of a full size specimen at the stress ratios of 0.1, 0.3 and 0.5 respectively. From this result, we can recognize that the fatigue crack propagation behavior of this material can be evaluated by using the half size specimens.

  7. Diffusion Bonding Beryllium to Reduced Activation Ferritic Martensitic Steel: Development of Processes and Techniques

    NASA Astrophysics Data System (ADS)

    Hunt, Ryan Matthew

    Only a few materials are suitable to act as armor layers against the thermal and particle loads produced by magnetically confined fusion. These candidates include beryllium, tungsten, and carbon fiber composites. The armor layers must be joined to the plasma facing components with high strength bonds that can withstand the thermal stresses resulting from differential thermal expansion. While specific joints have been developed for use in ITER (an experimental reactor in France), including beryllium to CuCrZr as well as tungsten to stainless steel interfaces, joints specific to commercially relevant fusion reactors are not as well established. Commercial first wall components will likely be constructed front Reduced Activation Ferritic Martensitic (RAFM) steel, which will need to be coating with one of the three candidate materials. Of the candidates, beryllium is particularly difficult to bond, because it reacts during bonding with most elements to form brittle intermetallic compounds. This brittleness is unacceptable, as it can lead to interface crack propagation and delamination of the armor layer. I have attempted to overcome the brittle behavior of beryllium bonds by developing a diffusion bonding process of beryllium to RAFM steel that achieves a higher degree of ductility. This process utilized two bonding aids to achieve a robust bond: a. copper interlayer to add ductility to the joint, and a titanium interlayer to prevent beryllium from forming unwanted Be-Cu intermetallics. In addition, I conducted a series of numerical simulations to predict the effect of these bonding aids on the residual stress in the interface. Lastly, I fabricated and characterized beryllium to ferritic steel diffusion bonds using various bonding parameters and bonding aids. Through the above research, I developed a process to diffusion bond beryllium to ferritic steel with a 150 M Pa tensile strength and 168 M Pa shear strength. This strength was achieved using a Hot Isostatic

  8. Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels

    PubMed Central

    Peixoto-Neves, Dieniffer; Wang, Qian; Leal-Cardoso, Jose H; Rossoni, Luciana V; Jaggar, Jonathan H

    2015-01-01

    Background and Purpose Eugenol, a vanilloid molecule found in some dietary plants, relaxes vasculature in part via an endothelium-dependent process; however, the mechanisms involved are unclear. Here, we investigated the endothelial cell-mediated mechanism by which eugenol modulates rat mesenteric artery contractility and systemic BP. Experimental Approach The isometric tension of rat mesenteric arteries (size 200–300 μm) was measured using wire myography; non-selective cation currents (ICat) were recorded in endothelial cells using patch clamp electrophysiology. Mean arterial pressure (MAP) and heart rate (HR) were determined in anaesthetized rats. Key Results Eugenol relaxed endothelium-intact arteries in a concentration-dependent manner a