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Sample records for activity level reduced

  1. 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.

  2. Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.

    PubMed

    von Leden, Ramona E; Curley, Lindsey C; Greenberg, Gian D; Hunsaker, Michael R; Willemsen, Rob; Berman, Robert F

    2014-03-01

    Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation. PMID:24462720

  3. 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

  4. 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

  5. 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

  6. Reduced cholesterol levels impair Smoothened activation in Smith–Lemli–Opitz syndrome

    PubMed Central

    Blassberg, Robert; Macrae, James I.; Briscoe, James; Jacob, John

    2016-01-01

    Smith–Lemli–Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. PMID:26685159

  7. Methylene blue reduceslevels and rescues early cognitive deficit by increasing proteasome activity

    PubMed Central

    Medina, David X.; Caccamo, Antonella; Oddo, Salvatore

    2010-01-01

    Promising results have emerged from a phase II clinical trial testing Methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduceslevels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin-and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action. PMID:20731659

  8. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  9. Body condition loss and increased serum levels of nonesterified fatty acids enhance progesterone levels at estrus and reduce estrous activity and insemination rates in postpartum dairy cows.

    PubMed

    Lüttgenau, J; Purschke, S; Tsousis, G; Bruckmaier, R M; Bollwein, H

    2016-03-01

    Data from 96 Holstein Friesian cows on a commercial dairy farm were used to investigate whether body condition and serum levels of nonesterified fatty acids (NEFAs) postpartum (pp) affect progesterone (P4) levels, estrous activity, and fertility in dairy cows. The examination period started 14 days before the expected calving date and ended either when a cow was inseminated or at a maximum of 90 days pp. Body condition score (BCS; 1-5 scale) and backfat thickness (BFT) were determined every 2 weeks. Blood for analysis of NEFA and P4 concentrations was sampled weekly during the first 35 days pp and then every 48 hours until an ovulation was observed. Transrectal ultrasonography of the ovaries started at 21 days pp and was performed after blood sampling. If cows were not inseminated because of silent ovulation, sampling and ultrasonography continued on Days 7, 14, and 18 after ovulation and again every 48 hours until the next ovulation. Estrous activity was continuously measured with the Heatime estrus detection system. Pregnancy controls were performed ultrasonographically 28 and 42 days after AI. Cows with increased NEFA levels at 28 days pp had an increased risk of maintaining minimum P4 levels above 0.4 ng/mL at first recognized estrus (P = 0.03). Higher NEFA levels at Day 7 were associated with lower probability for a cow to have elevated P4 levels (≥2 ng/mL) by Day 35 pp, indicating delayed commencement of luteal activity (C-LA). Estrous activity was not influenced (P > 0.10) by minimum P4 concentrations at estrus, but more animals with C-LA until Day 35 pp showed estrous activity compared to cows without C-LA throughout this period (P = 0.006). Estrous activity was lower in cows with a low BCS 14 days pp (P = 0.02) and with a low BFT 42 days pp (P = 0.03). Moreover, the probability to exhibit estrus was reduced with higher NEFA levels at 21 days pp (P = 0.01). Eighty-five cows were inseminated and 37 (44%) got pregnant after insemination. Higher NEFA levels

  10. Cilostazol Upregulates Autophagy via SIRT1 Activation: Reducing Amyloid-β Peptide and APP-CTFβ Levels in Neuronal Cells

    PubMed Central

    Lee, Hye Rin; Shin, Hwa Kyoung; Park, So Youn; Kim, Hye Young; Bae, Sun Sik; Lee, Won Suk; Rhim, Byung Yong; Hong, Ki Whan; Kim, Chi Dae

    2015-01-01

    Autophagy is a vital pathway for the removal of β-amyloid peptide (Aβ) and the aggregated proteins that cause Alzheimer’s disease (AD). We previously found that cilostazol induced SIRT1 expression and its activity in neuronal cells, and thus, we hypothesized that cilostazol might stimulate clearances of Aβ and C-terminal APP fragment β subunit (APP-CTFβ) by up-regulating autophagy.When N2a cells were exposed to soluble Aβ1–42, protein levels of beclin-1, autophagy-related protein5 (Atg5), and SIRT1 decreased significantly. Pretreatment with cilostazol (10–30 μM) or resveratrol (20 μM) prevented these Aβ1–42 evoked suppressions. LC3-II (a marker of mammalian autophagy) levels were significantly increased by cilostazol, and this increase was reduced by 3-methyladenine. To evoke endogenous Aβ overproduction, N2aSwe cells (N2a cells stably expressing human APP containing the Swedish mutation) were cultured in medium with or without tetracycline (Tet+ for 48 h and then placed in Tet- condition). Aβ and APP-CTFβ expressions were increased after 12~24 h in Tet- condition, and these increased expressions were significantly reduced by pretreating cilostazol. Cilostazol-induced reductions in the expressions of Aβ and APP-CTFβ were blocked by bafilomycin A1 (a blocker of autophagosome to lysosome fusion). After knockdown of the SIRT1 gene (to ~40% in SIRT1 protein), cilostazol failed to elevate the expressions of beclin-1, Atg5, and LC3-II, indicating that cilostazol increases these expressions by up-regulating SIRT1. Further, decreased cell viability induced by Aβ was prevented by cilostazol, and this inhibition was reversed by 3-methyladenine, indicating that the protective effect of cilostazol against Aβ induced neurotoxicity is, in part, ascribable to the induction of autophagy. In conclusion, cilostazol modulates autophagy by increasing the activation of SIRT1, and thereby enhances Aβ clearance and increases cell viability. PMID:26244661

  11. 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

  12. Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

    PubMed Central

    Wu, Shenghui; Fisher-Hoch, Susan P.; Reininger, Belinda; McCormick, Joseph B.

    2016-01-01

    Purpose To measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans. Methods Participants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities. Results One thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity. Conclusions Meeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors. PMID:27054324

  13. GABA-shunt enzymes activity in GH3 cells with reduced level of PMCA2 or PMCA3 isoform

    SciTech Connect

    Kowalski, Antoni

    2011-08-12

    Highlights: {yields} Suppression of PMCA2 or PMCA3 slows down proliferation of GH3 cells. {yields} PMCA2 suppression lowers the activity of GABA-shunt enzymes. {yields} PMCA3 suppression increases the expression of glutamate decarboxylase 65. {yields} PMCA2 and PMCA3 function appears to be linked to regulation of GABA metabolism. -- Abstract: GABA ({gamma}-aminobutyric acid) is important neurotransmitter and regulator of endocrine functions. Its metabolism involves three enzymes: glutamate decarboxylase (GAD65 and GAD67), GABA aminotransferase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). As many cellular processes GABA turnover can depend on calcium homeostasis, which is maintained by plasma membrane calcium ATPases (PMCAs). In excitable cells PMCA2 and PMCA3 isoforms are particularly important. In this study we focused on GABA-metabolizing enzymes expression and activity in rat anterior pituitary GH3 cells with suppressed expression of PMCA2 or PMCA3. We observed that PMCA3-reduced cells have increased GAD65 expression. Suppression of PMCA2 caused a decrease in total GAD and GABA-T activity. These results indicate that PMCA2 and PMCA3 presence may be an important regulatory factor in GABA metabolism. Results suggest that PMCA2 and PMCA3 function is rather related to regulation of GABA synthesis and degradation than supplying cells with metabolites, which can be potentially energetic source.

  14. Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: potential role of enhanced maternal immune activity?

    PubMed

    Canuti, Marta; Buka, Stephen; Jazaeri Farsani, Seyed Mohammad; Oude Munnink, Bas B; Jebbink, Maarten F; van Beveren, Nico J M; de Haan, Lieuwe; Goldstein, Jill; Seidman, Larry J; Tsuang, Ming T; Storosum, Jitschak G; van der Hoek, Lia

    2015-08-01

    Viral infections during the prenatal or early childhood periods are one of the environmental factors which might play an etiological role in psychoses. Several studies report higher antibody levels against viruses during pregnancy in blood of mothers of offspring with psychotic disorders, but the presence of such viruses has never been demonstrated. The goal of this study was to investigate the potential association between viral infections during pregnancy and progeny with psychotic disorders and, for this purpose, we performed a nested case-control study involving pregnant mothers of offspring with schizophrenia or bipolar disorder with psychotic features (cases, N=43) and pregnant women with healthy offspring (controls, N=95). Since several potential viral candidates have been suggested in prior work, a broad-spectrum virus detection system was necessary. A metagenomic analysis performed with the virus discovery method VIDISCA-454 revealed only common blood-associated viruses in all cohorts. However, a significantly lower viral prevalence was detected in the group of cases and in the sub-population of pregnant mothers of offspring with schizophrenia (p<0.05). Consistent with the existing inverse correlation between the level of these viruses and the immunocompetence of an individual, we hypothesized the presence of a higher immune activity during pregnancy in mothers whose offspring later develop a psychotic disorder as compared to controls. Combining our results with previously available literature data on antibody levels during the gestation period suggests that a more prominent maternal immune activity can be considered a risk factor for developing psychosis. PMID:26004694

  15. Maternal low-level lead exposure reduces the expression of PSA-NCAM and the activity of sialyltransferase in the hippocampi of neonatal rat pups.

    PubMed

    Hu, Qiansheng; Fu, Hongjun; Ren, Tieling; Wang, Shuyu; Zhou, Wei; Song, Hong; Han, Yifan; Dong, Shengzhang

    2008-07-01

    Highly polysialylated neural cell adhesion molecule (PSA-NCAM) is transiently expressed specifically in newly generated cells, and is important for cell migration and neurite outgrowth. Developmental lead (Pb) exposure has been considered to affect the expression of PSA-NCAM, which contributes to the neurotoxicity of Pb exposure. However, the effect of maternal low-level Pb exposure on the expression of PSA-NCAM in neonatal rat pups has not been reported. In the present study, female Wistar rats were exposed to vehicle or different dosages of lead chloride (0.5-4mM PbCl2) 2 weeks before and during pregnancy. This exposure protocol resulted in neonatal rat pups blood Pb levels up to 12.12+/-0.38 microg/dl, and hippocampal Pb levels up to 9.22+/-0.81 microg/g at postnatal day 1 (PND 1). Immunohistochemistry analysis and Western blot analysis revealed that the expressions of PSA-NCAM and NCAM in the hippocampi of neonatal rat pups at PND 1 were significantly reduced by the maternal low-level Pb exposures. Furthermore, the mRNA levels of NCAM and polysialyltransferases (STX and PST), measured by the fluorescent real-time quantitative RT-PCR, dosage-dependently and significantly decreased by 13.26-37.62%, 25.17-59.67%, and 10.78-47.81%, respectively. In addition, the sialyltransferase activity in neonatal rat pups was significantly reduced by 6.23-32.50% in the presence of the low-level Pb exposure, too. Taken together, these results suggest that maternal low-level Pb exposure reduces the expression of PSA-NCAM, NCAM, and the activity of sialyltransferase in the hippocampi of neonatal rat pups, which might contribute to the learning and memory impairments in the developmental pups following maternal low-level Pb exposure. PMID:18499259

  16. Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions.

    PubMed

    Grainger, D J; Mosedale, D E; Metcalfe, J C; Böttinger, E P

    2000-07-01

    Transforming growth factor-(beta) (TGF(beta)) has a wide range of activities on vascular cells and inflammatory cells, suggesting it may have different functions during various stages of atherogenesis. We report that mice heterozygous for the deletion of the tgfb1 gene (tgfb1(+/-) mice) have reduced levels of TGF(beta)1 in the artery wall until at least 8 weeks of age. On a normal mouse chow diet, the vascular endothelium of tgfb1(+/-) mice is indistinguishable from wild-type littermates, assessed by morphology and intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. In contrast, levels of the smooth muscle isoforms of actin and myosin in medial smooth muscle cells of tgfb1(+/-) mice are significantly reduced. Following feeding a cholesterol-enriched diet for 12 weeks, high levels of ICAM-1 and VCAM-1 were detected in the vascular endothelial cells of tgfb1(+/-) mice, but not wild-type mice. Furthermore, marked deposition of lipid into the artery wall was only observed in the tgfb1(+/-) mice on the cholesterol-enriched diet. These vascular lipid lesions were accompanied by local invasion of macrophages. We conclude that deletion of a single allele of the tgfb1 gene results in a reduced level of TGFbeta1 antigen in the aorta together with reduced smooth muscle cell differentiation, whereas the addition of a high fat dietary challenge is required to activate the vascular endothelium and to promote the formation of fatty streaks resembling early atherosclerosis in humans. PMID:10852815

  17. Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele

    PubMed Central

    Delorme, Richard; Betancur, Catalina; Chaste, Pauline; Kernéis, Solen; Stopin, Astrid; Mouren, Marie-Christine; Collet, Corinne; Bourgeron, Thomas; Leboyer, Marion; Launay, Jean-Marie

    2010-01-01

    Background The catechol-O-methyltransferase (COMT) gene is considered as a candidate gene in obsessive-compulsive disorder (OCD). Specifically, the COMT low-activity M158 allele has been suggested to be associated with OCD. However, there is no study reporting that COMT activity is decreased in OCD patients and that the decrease is mediated by the V158M polymorphism. Therefore, the purpose of our study was to assess COMT activity in OCD by measuring plasma levels of 3-O-methyl-dopa (3-OMD), which result from the methylation of levodopa by COMT, and to investigate the relationship between 3-OMD levels and the V158M polymorphism. We also examined whether 3-OMD levels represented an endophenotype, associated with the genetic liability to OCD, by assessing unaffected relatives of OCD patients. Method We assessed plasma 3-OMD levels in a sample of drug-free OCD probands (n = 34) and their unaffected parents (n = 63), and compared them with controls (n = 85). The COMT V158M polymorphism was genotyped in all participants. Results Lower plasma 3-OMD levels were found in OCD probands and their unaffected parents compared to controls. The COMT M158 allele was associated with reduced plasma 3-OMD levels in a co-dominant manner, both in OCD probands and their relatives, but not in controls. Conclusion Our results suggest that COMT activity could act as a limiting factor for the production of 3-OMD in OCD patients and in their relatives. These findings further support a role of COMT in the susceptibility to OCD and provide evidence that 3-OMD levels could represent an endophenotype in OCD. PMID:19676096

  18. Reduced levels of mitochondrial complex I subunit NDUFB8 and linked complex I + III oxidoreductase activity in the TgCRND8 mouse model of Alzheimer's disease.

    PubMed

    Francis, Beverly M; Yang, Jimao; Song, Byung Jun; Gupta, Saurabh; Maj, Mary; Bazinet, Richard P; Robinson, Brian; Mount, Howard T J

    2014-01-01

    Bioenergetic failure is a feature of Alzheimer's disease (AD). We examined mitochondrial function in the amyloid-β protein precursor transgenic 'TgCRND8' mouse model of AD. Activities of NADH: cytochrome c reductase (complex I + III) and cytochrome oxidase (complex IV) of the electron transport chain, as well as those of α-ketoglutarate dehydrogenase (α-KGDH) and pyruvate dehydrogenase (PDH) were assessed in brains of 45 week-old mice. Complex I + III activity was reduced by almost 50%, whereas complex IV, α-KGDH, and PDH activities were unaffected. Reduced activity coincided with decreased expression of NDUFB8, a nuclear-DNA encoded subunit integral to the assembly of complex I. The composition and availability of cardiolipin, a major phospholipid in inner mitochondrial membranes, was not altered. To determine whether mitochondrial output is affected by the selective reduction in complex I + III activity, we examined tissue levels of high-energy phosphates. ATP was maintained whereas creatine increased in the cortex and hippocampus. These results suggest disruption of complex I function and the likely role of creatine in sustaining ATP at late stages of dysfunction in TgCRND8 mice. PMID:24217272

  19. Treatment with PPARα Agonist Clofibrate Inhibits the Transcription and Activation of SREBPs and Reduces Triglyceride and Cholesterol Levels in Liver of Broiler Chickens

    PubMed Central

    Zhang, Lijun; Li, Chunyan; Wang, Fang; Zhou, Shenghua; Shangguan, Mingjun; Xue, Lina; Zhang, Bianying; Ding, Fuxiang; Hui, Dequan; Liang, Aihua; He, Dongchang

    2015-01-01

    PPARα agonist clofibrate reduces cholesterol and fatty acid concentrations in rodent liver by an inhibition of SREBP-dependent gene expression. In present study we investigated the regulation mechanisms of the triglyceride- and cholesterol-lowering effect of the PPARα agonist clofibrate in broiler chickens. We observed that PPARα agonist clofibrate decreases the mRNA and protein levels of LXRα and the mRNA and both precursor and nuclear protein levels of SREBP1 and SREBP2 as well as the mRNA levels of the SREBP1 (FASN and GPAM) and SREBP2 (HMGCR and LDLR) target genes in the liver of treated broiler chickens compared to control group, whereas the mRNA level of INSIG2, which inhibits SREBP activation, was increased in the liver of treated broiler chickens compared to control group. Taken together, the effects of PPARα agonist clofibrate on lipid metabolism in liver of broiler chickens involve inhibiting transcription and activation of SREBPs and SREBP-dependent lipogenic and cholesterologenic gene expression, thereby resulting in a reduction of the triglyceride and cholesterol levels in liver of broiler chickens. PMID:26693219

  20. 4-Phenylbutyric acid reduces mutant-TGFBIp levels and ER stress through activation of ERAD pathway in corneal fibroblasts of granular corneal dystrophy type 2.

    PubMed

    Choi, Seung-Il; Lee, Eunhee; Jeong, Jang Bin; Akuzum, Begum; Maeng, Yong-Sun; Kim, Tae-Im; Kim, Eung Kweon

    2016-09-01

    Granular corneal dystrophy type 2 (GCD2) is caused by a point mutation (R124H) in the transforming growth factor β-induced (TGFBI) gene. In GCD2 corneal fibroblasts, secretion of the accumulated mutant TGFBI-encoded protein (TGFBIp) is delayed via the endoplasmic reticulum (ER)/Golgi-dependent secretory pathway. However, ER stress as the pathogenic mechanism underlying GCD2 has not been fully characterized. The aim of this study was to confirm whether ER stress is linked to GCD2 pathogenesis and whether the chemical chaperone, 4-phenylbutyric acid (4-PBA), could be exploited as a therapy for GCD2. We found that the ER chaperone binding immunoglobulin protein (BiP) and the protein disulfide isomerase (PDI) were elevated in GCD2. Western bolt analysis also showed a significant increase in both the protein levels and the phosphorylation of the key ER stress kinases, inositol-requiring enzyme 1α (IRE1α) and double stranded RNA activated protein kinase (PKR)-like ER kinase, as well as in levels of their downstream targets, X box-binding protein 1 (XBP1) and activating transcription factor 4, respectively, in GCD2 corneal fibroblasts. GCD2 cells were found to be more susceptible to ER stress-induced cell death than were wild-type corneal fibroblasts. Treatment with 4-PBA considerably reduced the levels of BiP, IRE1α, and XBP1 in GCD2 cells; notably, 4-PBA treatment significantly reduced the levels of TGFBIp without change in TGFBI mRNA levels. In addition, TGFBIp levels were significantly reduced under ER stress and this reduction was considerably suppressed by the ubiquitin proteasome inhibitor MG132, indicating TGFBIp degradation via the ER-associated degradation pathway. Treatment with 4-PBA not only protected against the GCD2 cell death induced by ER stress but also significantly suppressed the MG132-mediated increase in TGFBIp levels under ER stress. Together, these results suggest that ER stress might comprise an important factor in GCD2 pathophysiology and

  1. Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States.

    PubMed

    Keyes, Katherine M; Cheslack-Postava, Keely; Westhoff, Carolyn; Heim, Christine M; Haloossim, Michelle; Walsh, Kate; Koenen, Karestan

    2013-11-01

    An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted. PMID:24043440

  2. TERT alleviates irradiation-induced late rectal injury by reducing hypoxia-induced ROS levels through the activation of NF-κB and autophagy.

    PubMed

    Liu, Qi; Sun, Yong; Lv, Yuefeng; Le, Ziyu; Xin, Yuhu; Zhang, Ping; Liu, Yong

    2016-09-01

    The hypoxic microenvironment which is present following irradiation has been proven to promote radiation-induced injury to normal tissues. Previous studies have demonstrated that telomerase reverse transcriptase (TERT) is regulated by hypoxia, and that it plays a protective role in the process of wound repair. However, its effects on radiation-induced injury remain unclear. In this study, we examined the effects of human TERT on irradiation-induced late rectal injury in fibroblasts under hypoxic conditions. We also performed in vivo experiments. The rectums of 5-week‑old female C57BL/6N mice were irradiated locally with a single dose of 25 Gy. We then examined the fibrotic changes using hematoxylin and eosin staining, and Masson's staining. The expression of hypoxia inducible factor-1α (HIF-1α) and TERT was analyzed by immunohistochemistry. In in vitro experiments, apoptosis, reactive oxygen species (ROS) production and the autophagy level induced by exposure to hypoxia were assayed in fibroblasts. The association between TERT, nuclear factor-κB (NF-κB) and the autophagy level was examined by western blot analysis. The antioxidant effects of TERT were examined on the basis of the ratio of glutathione to glutathione disulfide (GSH/GSSG) and mitochondrial membrane potential. Rectal fibrosis was induced significantly at 12 weeks following irradiation. The HIF-1α and TERT expression levels increased in the fibrotic region. The TERT‑overexpressing fibroblasts (transfected with an hTERT-expressing lentiviral vector) exhibited reduced apoptosis, reduced ROS production, a higher autophagy level, a higher GSH/GSSG ratio and stable mitochondrial membrane potential compared with the fibroblasts in which TERT had been silenced by siRNA. NF-κB was activated by TERT, and the inhibition of TERT reduced the autophagy level in the fibroblasts. These results demonstrate that TERT decreases cellular ROS production, while maintaining mitochondrial function and

  3. TERT alleviates irradiation-induced late rectal injury by reducing hypoxia-induced ROS levels through the activation of NF-κB and autophagy

    PubMed Central

    Liu, Qi; Sun, Yong; Lv, Yuefeng; Le, Ziyu; Xin, Yuhu; Zhang, Ping; Liu, Yong

    2016-01-01

    The hypoxic microenvironment which is present following irradiation has been proven to promote radiation-induced injury to normal tissues. Previous studies have demonstrated that telomerase reverse transcriptase (TERT) is regulated by hypoxia, and that it plays a protective role in the process of wound repair. However, its effects on radiation-induced injury remain unclear. In this study, we examined the effects of human TERT on irradiation-induced late rectal injury in fibroblasts under hypoxic conditions. We also performed in vivo experiments. The rectums of 5-week-old female C57BL/6N mice were irradiated locally with a single dose of 25 Gy. We then examined the fibrotic changes using hematoxylin and eosin staining, and Masson's staining. The expression of hypoxia inducible factor-1α (HIF-1α) and TERT was analyzed by immunohistochemistry. In in vitro experiments, apoptosis, reactive oxygen species (ROS) production and the autophagy level induced by exposure to hypoxia were assayed in fibroblasts. The association between TERT, nuclear factor-κB (NF-κB) and the autophagy level was examined by western blot analysis. The antioxidant effects of TERT were examined on the basis of the ratio of glutathione to glutathione disulfide (GSH/GSSG) and mitochondrial membrane potential. Rectal fibrosis was induced significantly at 12 weeks following irradiation. The HIF-1α and TERT expression levels increased in the fibrotic region. The TERT-overexpressing fibroblasts (transfected with an hTERT-expressing lentiviral vector) exhibited reduced apoptosis, reduced ROS production, a higher autophagy level, a higher GSH/GSSG ratio and stable mitochondrial membrane potential compared with the fibroblasts in which TERT had been silenced by siRNA. NF-κB was activated by TERT, and the inhibition of TERT reduced the autophagy level in the fibroblasts. These results demonstrate that TERT decreases cellular ROS production, while maintaining mitochondrial function and protecting the

  4. Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study

    PubMed Central

    2012-01-01

    Background Most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients’ preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial. Methods Patients aged 60–74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared. Results Two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population. Conclusions This study has confirmed and amplified recently published factors involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to

  5. Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ(1-42)-induced rat model of Alzheimer's disease.

    PubMed

    Turunc Bayrakdar, E; Uyanikgil, Y; Kanit, L; Koylu, E; Yalcin, A

    2014-02-01

    The underlying mechanisms of Alzheimer's Disease (AD) are still unclear. It is suggested that poly(ADP-ribose) polymerase-1 (PARP-1) overactivation can cause neuroinflammation and cell death. In this study we searched the effects of nicotinamide (NA), endogenous PARP-1 inhibitor, on oxidative stress, apoptosis, and the regulation of PARP-1 and nuclear factor kappa B (NF-κB) in amyloid beta peptide (1-42) (Aβ(1-42))-induced neurodegeneration. Sprague-Dawley rats were divided into four groups as control, Aβ(1-42), Aβ(1-42) + NA(100 and 500 mg/kg). All groups were stereotaxically injected bilaterally into the hippocampus with Aβ(1-42) or saline. After surgery NA administrations were made intraperitoneally (ip) for 7 days. In order to investigate the effects of Aβ(1-42) and NA, protein carbonyls, lipid peroxidation, reactive oxygen species (ROS) production, glutathione (GSH) levels, activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), mitochondrial function, mRNA and protein levels of PARP-1, NF-κB, p53, Bax, and Bcl-2 were measured in specific brain regions such as cortex and hippocampus. Aβ(1-42) treatment only increased the oxidative stress parameters and caused decline in antioxidant enzyme activities, mitochondrial function, and GSH levels. Also, overexpression of PARP-1, NF-κB, p53, Bax, and the decreased levels of Bcl-2 were observed in Aβ(1-42)-treated group. NA treatments against Aβ(1-42)-upregulated Bcl-2 and downregulated PARP-1, NF-κB, p53, and Bax levels. NA treatments also decreased the oxidative stress parameters and elevated antioxidant enzyme activities, GSH levels, and mitochondrial function against Aβ(1-42) treatment. These data suggest that NA may have a therapeutic potential in neurodegenerative processes due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activity. PMID:24151909

  6. Organizational-Level Strategies With or Without an Activity Tracker to Reduce Office Workers’ Sitting Time: Rationale and Study Design of a Pilot Cluster-Randomized Trial

    PubMed Central

    Fjeldsoe, Brianna S; Young, Duncan C; Winkler, Elisabeth A H; Dunstan, David W; Straker, Leon M; Brakenridge, Christian J; Healy, Genevieve N

    2016-01-01

    Background The office workplace is a key setting in which to address excessive sitting time and inadequate physical activity. One major influence on workplace sitting is the organizational environment. However, the impact of organizational-level strategies on individual level activity change is unknown. Further, the emergence of sophisticated, consumer-targeted wearable activity trackers that facilitate real-time self-monitoring of activity, may be a useful adjunct to support organizational-level strategies, but to date have received little evaluation in this workplace setting. Objective The aim of this study is to evaluate the feasibility, acceptability, and effectiveness of organizational-level strategies with or without an activity tracker on sitting, standing, and stepping in office workers in the short (3 months, primary aim) and long-term (12 months, secondary aim). Methods This study is a pilot, cluster-randomized trial (with work teams as the unit of clustering) of two interventions in office workers: organizational-level support strategies (eg, visible management support, emails) or organizational-level strategies plus the use of a waist-worn activity tracker (the LUMOback) that enables self-monitoring of sitting, standing, and stepping time and enables users to set sitting and posture alerts. The key intervention message is to ‘Stand Up, Sit Less, and Move More.’ Intervention elements will be implemented from within the organization by the Head of Workplace Wellbeing. Participants will be recruited via email and enrolled face-to-face. Assessments will occur at baseline, 3, and 12 months. Time spent sitting, sitting in prolonged (≥30 minute) bouts, standing, and stepping during work hours and across the day will be measured with activPAL3 activity monitors (7 days, 24 hours/day protocol), with total sitting time and sitting time during work hours the primary outcomes. Web-based questionnaires, LUMOback recorded data, telephone interviews, and focus

  7. Reduced plasma pyrophosphate levels in hemodialysis patients.

    PubMed

    Lomashvili, Koba A; Khawandi, Wassim; O'Neill, W Charles

    2005-08-01

    Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was demonstrated recently that endogenous production of PPi prevents calcification of rat aorta that are cultured in high concentrations of calcium and phosphate. For determining whether PPi metabolism is altered in hemodialysis patients, plasma levels and dialytic clearance of PPi were measured in stable hemodialysis patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 microM in 38 clinically stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not altered in dialysis patients. There was a weak inverse correlation with age in normal individuals but not in dialysis patients. Plasma [PPi] in dialysis patients was correlated with plasma [PO4(3-)] (r = 0.56) but not with [Ca2+], parathyroid hormone, or the dose of dialysis, and levels did not vary between interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m2 cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was 43 +/- 5 micromol, consistent with a similar in vivo clearance. Cleared PPi was greater than the plasma pool but less than the estimated extracellular fluid pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular PPi is removed as well. It is concluded that plasma [PPi] is reduced in hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some patients were below those that have previously been shown to prevent calcification of vessels in culture, suggesting that altered PPi metabolism could contribute to vascular calcification in hemodialysis patients. PMID:15958726

  8. Mice expressing reduced levels of hepatic glucose-6-phosphatase-α activity do not develop age-related insulin resistance or obesity.

    PubMed

    Kim, Goo-Young; Lee, Young Mok; Cho, Jun-Ho; Pan, Chi-Jiunn; Jun, Hyun Sik; Springer, Danielle A; Mansfield, Brian C; Chou, Janice Y

    2015-09-15

    Glycogen storage disease type-Ia (GSD-Ia) is caused by a lack of glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. We have shown that gene therapy mediated by a recombinant adeno-associated virus (rAAV) vector expressing human G6Pase-α normalizes blood glucose homeostasis in the global G6pc knockout (G6pc(-/-)) mice for 70-90 weeks. The treated G6pc(-/-) mice expressing 3-63% of normal hepatic G6Pase-α activity (AAV mice) produce endogenous hepatic glucose levels 61-68% of wild-type littermates, have a leaner phenotype and exhibit fasting blood insulin levels more typical of young adult mice. We now show that unlike wild-type mice, the lean AAV mice have increased caloric intake and do not develop age-related obesity or insulin resistance. Pathway analysis shows that signaling by hepatic carbohydrate response element binding protein that improves glucose tolerance and insulin signaling is activated in AAV mice. In addition, several longevity factors in the calorie restriction pathway, including the NADH shuttle systems, NAD(+) concentrations and the AMP-activated protein kinase/sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway are upregulated in the livers of AAV mice. The finding that partial restoration of hepatic G6Pase-α activity in GSD-Ia mice not only attenuates the phenotype of hepatic G6Pase-α deficiency but also prevents the development of age-related obesity and insulin resistance seen in wild-type mice may suggest relevance of the G6Pase-α enzyme to obesity and diabetes. PMID:26089201

  9. Free heme pool and activity of key enzyme of heme synthesis in the rat liver under action of agents affecting reduced glutathione level.

    PubMed

    Barannik, T V; Inshina, N M; Kaliman, P A

    2005-01-01

    The decrease of GSH level in the rat liver was found to be accompanied by an increase of tryptophan 2,3-dioxygenase (TDO) heme saturation during first hours after HgCl2, phenylhydrazine (Ph) injection or rhabdomyolysis (the coefficient of correlation -0.978). The activity of the key enzyme of heme synthesis--5-aminolevulinate synthase (ALAS) was 2.5-fold increased in the first hours after Ph injection and rhabdomyolysis. Glutathione injection in vivo as well as CdCl2 caused the increase of GSH content and the inhibition of ALAS. The coefficient of correlation for GSH content and ALAS activity under the action of agents altering both these parameters (CdCl2, Ph, GSH injection and rhabdomyolysis) is 0.938. Taking into account the presence of heme regulatory motif with conserved cystein in many proteins, including ALAS and TDO (accession number in SwissProt database AAH61793 and P21643, respectively), the link between alterations of GSH content, ALAS activity and heme saturation of TDO in the rat liver could be proposed. The further experiments should be performed in order to elucidate the mechanisms of GSH level influence on free heme pool formation in the liver cells. PMID:16846079

  10. Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans-zeatin in Eucalyptus globulus trees.

    PubMed

    González, Alberto; Contreras, Rodrigo A; Zúiga, Gustavo; Moenne, Alejandra

    2014-01-01

    Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an increase in NADPH, ascorbate and glutathione levels and activation of the thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance photosynthesis, basal metabolism and growth. In order to analyze whether the reducing redox status and the activation of thioredoxin reductase (TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees were treated with water (control), with OC kappa, or with inhibitors of ascorbate synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC kappa, and cultivated for four additional months. Eucalyptus trees treated with OC kappa showed an increase in the levels of the auxin indole 3-acetic acid (IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition, treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox status and the activation of TRR/TRX system induced by OC kappa increased the levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation of growth in Eucalyptus trees. PMID:25140447

  11. Diminished acyl-CoA synthetase isoform 4 activity in INS 832/13 cells reduces cellular epoxyeicosatrienoic acid levels and results in impaired glucose-stimulated insulin secretion.

    PubMed

    Klett, Eric L; Chen, Shufen; Edin, Matthew L; Li, Lei O; Ilkayeva, Olga; Zeldin, Darryl C; Newgard, Christopher B; Coleman, Rosalind A

    2013-07-26

    Glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells is potentiated by fatty acids (FA). The initial step in the metabolism of intracellular FA is the conversion to acyl-CoA by long chain acyl-CoA synthetases (Acsls). Because the predominantly expressed Acsl isoforms in INS 832/13 cells are Acsl4 and -5, we characterized the role of these Acsls in beta-cell function by using siRNA to knock down Acsl4 or Acsl5. Compared with control cells, an 80% suppression of Acsl4 decreased GSIS and FA-potentiated GSIS by 32 and 54%, respectively. Knockdown of Acsl5 did not alter GSIS. Acsl4 knockdown did not alter FA oxidation or long chain acyl-CoA levels. With Acsl4 knockdown, incubation with 17 mm glucose increased media epoxyeicosatrienoic acids (EETs) and reduced cell membrane levels of EETs. Further, exogenous EETs reduced GSIS in INS 832/13 cells, and in Acsl4 knockdown cells, an EET receptor antagonist partially rescued GSIS. These results strongly suggest that Acsl4 activates EETs to form EET-CoAs that are incorporated into glycerophospholipids, thereby sequestering EETs. Exposing INS 832/13 cells to arachidonate or linoleate reduced Acsl4 mRNA and protein expression and reduced GSIS. These data indicate that Acsl4 modulates GSIS by regulating the levels of unesterified EETs and that arachidonate controls the expression of its activator Acsl4. PMID:23766516

  12. 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.

  13. 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

  14. 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

  15. 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.)

  16. 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.

  17. 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

  18. Low stimulus environments: reducing noise levels in continuing care.

    PubMed

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  19. Low stimulus environments: reducing noise levels in continuing care

    PubMed Central

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  20. Unsaturated fatty acids supplementation reduces blood lead level in rats.

    PubMed

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: "super lecithin" (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  1. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    PubMed Central

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: “super lecithin” (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  2. 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

  3. 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

  4. 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

  5. Enzymatic treatment of peanut kernels to reduce allergen levels.

    PubMed

    Yu, Jianmei; Ahmedna, Mohamed; Goktepe, Ipek; Cheng, Hsiaopo; Maleki, Soheila

    2011-08-01

    This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernels as affected by processing conditions. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicators of process effectiveness. Enzymatic treatment effectively reduced Ara h 1 and Ara h 2 in roasted peanut kernels by up to 100% under optimal conditions. For instance, treatment of roasted peanut kernels with α-chymotrypsin and trypsin for 1-3h significantly increased the solubility of peanut protein while reducing Ara h 1 and Ara h 2 in peanut kernel extracts by 100% and 98%, respectively, based on ELISA readings. Ara h 1 and Ara h 2 levels in peanut protein extracts were inversely correlated with protein solubility in roasted peanut. Blanching of kernels enhanced the effectiveness of enzyme treatment in roasted peanuts but not in raw peanuts. The optimal concentration of enzyme was determined by response surface to be in the range of 0.1-0.2%. No consistent results were obtained for raw peanut kernels since Ara h 1 and Ara h 2 increased in peanut protein extracts under some treatment conditions and decreased in others. PMID:25214091

  6. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    PubMed

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients. PMID:14637240

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Calcium Deficiency Reduces Circulating Levels of FGF23

    PubMed Central

    Rodriguez-Ortiz, María E.; Lopez, Ignacio; Muñoz-Castañeda, Juan R.; Martinez-Moreno, Julio M.; Ramírez, Alan Peralta; Pineda, Carmen; Canalejo, Antonio; Jaeger, Philippe; Aguilera-Tejero, Escolastico; Felsenfeld, Arnold; Almaden, Yolanda

    2012-01-01

    Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. PMID:22581996

  12. Population Characteristics May Reduce the Levels of Individual Call Identity

    PubMed Central

    Delgado, María del Mar; Caferri, Eleonora; Méndez, Maria; Godoy, José A.; Campioni, Letizia; Penteriani, Vincenzo

    2013-01-01

    Individual variability influences the demographic and evolutionary dynamics of spatially structured populations, and conversely ecological and evolutionary dynamics provide the context under which variations at the individual level occur. Therefore, it is essential to identify and characterize the importance of the different factors that may promote or hinder individual variability. Animal signaling is a prime example of a type of behavior that is largely dependent on both the features of individuals and the characteristics of the population to which they belong. After 10 years studying the dynamics of a population of a long-lived species, the eagle owl (Bubo bubo), we investigated the emergence and maintenance of traits that reveal individual identity by focusing on vocal features. We found that individuals inhabiting a high density population characterized by a relative lack of heterogeneity (in terms of prey availability and breeding success) among breeding sites might be selected for reducing the levels of identity. Two non-mutually exclusive hypotheses may explain the structural call patterns we detected: (1) similarity in calls may be principally a consequence of the particular characteristics of the population; and (2) high density may encourage individuals to mimic each other’s vocalizations in a cascade effect, leading to a widespread and unique communication network. PMID:24204869

  13. 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

  14. 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

  15. 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

  16. 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

  17. Birth Order and Activity Level in Children.

    ERIC Educational Resources Information Center

    Eaton, Warren O.; And Others

    1989-01-01

    Studied 7,018 children between birth and 7 years and 81 children of 5-8 years to test the hypothesis that birth order is negatively related to motor activity level. Activity level declined linearly across birth position, so that early-borns were rated as more active than later-borns. (RJC)

  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. Reducing ethylene levels along the food supply chain: a key to reducing food waste?

    PubMed

    Blanke, Michael M

    2014-09-01

    Excessive waste along the food supply chain of 71 (UK, Netherlands) to 82 (Germany) kg per head per year sparked widespread criticism of the agricultural food business and provides a great challenge and task for all its players and stakeholders. Origins of this food waste include private households, restaurants and canteens, as well as supermarkets, and indicate that 59-65% of this food waste can be avoided. Since ∼50% of the food waste is fruit and vegetables, monitoring and control of their natural ripening gas - ethylene - is suggested here as one possible key to reducing food waste. Ethylene accelerates ripening of climacteric fruits, and accumulation of ethylene in the supply chain can lead to fruit decay and waste. While ethylene was determined using a stationary gas chromatograph with gas cylinders, the new generation of portable sensor-based instruments now enables continuous in situ determination of ethylene along the food chain, a prerequisite to managing and maintaining the quality and ripeness of fruits and identifying hot spots of ethylene accumulation along the supply chain. Ethylene levels were measured in a first trial, along the supply chain of apple fruit from harvest to the consumer, and ranged from 10 ppb in the CA fruit store with an ethylene scrubber, 70 ppb in the fruit bin, to 500 ppb on the sorting belt in the grading facility, to ppm levels in perforated plastic bags of apples. This paper also takes into account exogenous ethylene originating from sources other than the fruit itself. Countermeasures are discussed, such as the potential of breeding for low-ethylene fruit, applications of ethylene inhibitors (e.g. 1-MCP) and absorber strips (e.g. 'It's Fresh', Ryan'), packages (e.g. 'Peakfresh'), both at the wholesale and retail level, vents and cooling for the supply chain, sale of class II produce ('Wunderlinge'), collection (rather than waste) of produce on the 'sell by' date ('Die Tafel') and whole crop purchase (WCP) to aid reducing

  20. 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

  1. 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

  2. Reducing nursing students' anxiety level and increasing retention of materials.

    PubMed

    Phillips, A P

    1988-01-01

    The purpose of this descriptive study is to examine the effects active learning, collaboration and modified group testing have on reducing students' anxiety and increasing learning and retention of material. Subjects consist of 34 associate degree nursing students enrolled in the Advanced Adult Health nursing class at North Georgia College. Most of the students are married, have children and work part time. A self-reporting questionnaire suggests a reduction of the students' anxiety during the quarter. The attitudinal questionnaire reveals an atmosphere of collaboration among peers. Data evaluating learning and retention of material were analyzed using the parametric (T-test) and nonparametric (Wiley Rank Sum test) methods. Examination of the Null Hypotheses I and II suggests there were increased learning and retention of material as evidenced by higher grades on the comprehensive final examination than on the quizzes given after presentation of content. Principles of andragogy as defined by Knowles (1980) and cooperation with peers as described by Johnson, Johnson, Holabec, and Roy (1984), Johnson, Johnson, and Maruyama (1983), and Johnson and Johnson (1975) form the theoretical foundation. PMID:2828575

  3. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    PubMed

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P < 0.05 vs. vehicle). A significant 20% reduction in hepatic LDL receptor protein expression was also observed with empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  4. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  5. 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

  6. Reduced cadmium levels in human kidney cortex in sweden.

    PubMed Central

    Friis, L; Petersson, L; Edling, C

    1998-01-01

    Environmental pollution with the nephrotoxic metal cadmium is considered a potential health risk for the general population. In 1976 it was reported that the cadmium concentration in human kidney cortex in Sweden had increased in parallel with increasing levels in soil and grain during the twentieth century. Since the cadmium concentration in farming lands is still increasing, the present study was undertaken to further elucidate whether the cadmium concentration in the kidney is still increasing. Kidney cortex biopsies were collected at 171 autopsies of victims to sudden and accidental death during 1995 and 1996, and the cadmium concentrations were determined and compared with previously published Swedish data obtained from forensic autopsies. The geometric mean cadmium concentration in kidney cortex in subjects 40 years of age and younger was about 40% of the concentration found in the 1970s, while the reduction was less pronounced among older people. The highest individual concentration of cadmium was 41.5 microg/g wet weight (ww). The geometric mean concentration was less than 14 microg/g ww at ages around 50 years of age, when the cadmium concentration in kidney cortex is highest, as compared with approximately 20 microg/g ww in the 1970s. There was also a reduction in cadmium concentrations among nonsmokers; thus, a decrease in tobacco smoking in Sweden during the last decades is not the only explanation for the reduction of cadmium in the kidney cortex. Other reasons for this reduction could be changes in dietary habits and reduced cadmium contamination from Swedish industries. Images Figure 1 PMID:9485480

  7. Engagement in Pleasant Activities and Depression Level

    ERIC Educational Resources Information Center

    Lewinsohn, Peter M.

    1975-01-01

    Previous studies have shown a low rate of engagement in pleasant activities to be a concomitant of depression. The crucial question addressed by the Hammen and Glass study (1975) is whether an increase in pleasant-activity level will produce a decrease in depression level. (Editor)

  8. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.

    PubMed

    Nanthirudjanar, Tharnath; Furumoto, Hidehiro; Zheng, Jiawen; Kim, Young-Il; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2015-11-01

    Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia. PMID:26399511

  9. 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

  10. Factors Influencing Cypriot Children's Physical Activity Levels

    ERIC Educational Resources Information Center

    Loucaides, Constantinos A.; Chedzoy, Sue M.

    2005-01-01

    The purpose of this paper is to present selected findings from a larger study, which set out to examine the physical activity levels of Cypriot primary school children and determinants of their activity. Twenty parents of children who obtained high and low activity scores based on pedometer counts and self-reports scores were interviewed. By…

  11. β-asarone increases MEF2D and TH levels and reduces α-synuclein level in 6-OHDA-induced rats via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway: Chaperone-mediated autophagy activation, macroautophagy inhibition and HSP70 up-expression.

    PubMed

    Huang, Liping; Deng, Minzhen; He, Yuping; Lu, Shiyao; Liu, Shu; Fang, Yongqi

    2016-10-15

    Inactive myocyte enhancer factor 2D (MEF2D) and alpha-synuclein (α-syn) aggregation will cause neuronal death. MEF2D or α-syn degradation is also associated with macroautophagy, chaperone-mediated autophagy (CMA) and heat-shock protein 70 (HSP70). We found that β-asarone had positive effects on treating 6-hydroxydopamine (6-OHDA)-induced rats, but mechanisms of β-asarone affecting on MEF2D and α-syn via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway remain unclear. Unilateral 6-OHDA injection into the medial forebrain bundle was used to create PD rats, which were divided into four groups and administered for 30days: 6-OHDA model group, MEF2D inhibitor-treated group (SB203580, 0.5mg/kg, i.p.), MEF2D activator-treated group (LiCl, 100mg/kg, i.p.), β-asarone-treated group (15mg/kg, p.o.). Expressions of tyrosine hydroxylase (TH), α-syn, heat-shock cognate protein 70 (HSC70), lysosome-associated membrane protein type 2a (LAMP-2A), MEF2D, HSP70, Beclin-1, light chain 3B (LC3B) and p62 in the mesencephalon were measured after 30-day administration. α-syn, Beclin-1 and LC3B levels were higher in the 6-OHDA model group, while TH, MEF2D, HSC70, LAMP-2A, p62 levels were lower compared to the sham-operated group. Our results also showed thatβ-asarone treatment reduced protein and mRNA levels of α-syn, Beclin-1 and LC3B, but increased HSP70, TH, MEF2D, HSC70, LAMP-2A and p62 levels compared to the 6-OHDA model group. Additionally, certain correlations among α-syn, TH, Beclin-1, LC3B, p62, HSP70, LAMP-2A and MEF2D were also discovered in this study. These findings suggested that β-asarone treatment could increase MEF2D and TH as well as reduce α-syn to protect against 6-OHDA induced damage in PD rat mesencephalon via modulating the HSP70/MAPK/MEF2D/Beclin-1 pathway. PMID:27444243

  12. Enzymatic treatment of peanut kernels to reduce allergen levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernel by processing conditions, such as, pretreatment with heat and proteolysis at different enzyme concentrations and treatment times. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicator...

  13. 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

  14. 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

  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. 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)

  17. 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...

  18. Health Promotion to Reduce Blood Pressure Level among Older Blacks.

    ERIC Educational Resources Information Center

    Haber, David

    1986-01-01

    Low-income Black elders completed a 10-week health promotion program for the purpose of lowering or stabilizing blood pressure levels. Comparisons were made between classes that met weekly versus three times a week, and between yoga and aerobics formats. A peer-led program was developed that continued for 10 months after the professionally-led…

  19. 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

  20. 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

  1. Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

    PubMed

    Santana-Martínez, R A; Galván-Arzáte, S; Hernández-Pando, R; Chánez-Cárdenas, M E; Avila-Chávez, E; López-Acosta, G; Pedraza-Chaverrí, J; Santamaría, A; Maldonado, P D

    2014-07-11

    Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities. PMID:24814729

  2. 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

  3. 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

  4. Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels

    PubMed Central

    Bartolome, Fernando; Wu, Hsiu-Chuan; Burchell, Victoria S.; Preza, Elisavet; Wray, Selina; Mahoney, Colin J.; Fox, Nick C.; Calvo, Andrea; Canosa, Antonio; Moglia, Cristina; Mandrioli, Jessica; Chiò, Adriano; Orrell, Richard W.; Houlden, Henry; Hardy, John; Abramov, Andrey Y.; Plun-Favreau, Helene

    2013-01-01

    Summary Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget’s disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%–2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death. PMID:23498975

  5. Sulforaphane Restores Cellular Glutathione Levels and Reduces Chronic Periodontitis Neutrophil Hyperactivity In Vitro

    PubMed Central

    Dias, Irundika H. K.; Chapple, Ian L. C.; Milward, Mike; Grant, Melissa M.; Hill, Eric; Brown, James; Griffiths, Helen R.

    2013-01-01

    The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2. - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients’ neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2. - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. PMID:23826097

  6. 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

  7. Reduced striatal adenosine A2A receptor levels define a molecular subgroup in schizophrenia.

    PubMed

    Villar-Menéndez, Izaskun; Díaz-Sánchez, Sara; Blanch, Marta; Albasanz, José Luis; Pereira-Veiga, Thais; Monje, Alfonso; Planchat, Luis Maria; Ferrer, Isidre; Martín, Mairena; Barrachina, Marta

    2014-04-01

    Schizophrenia (SZ) is a mental disorder of unknown origin. Some scientific evidence seems to indicate that SZ is not a single disease entity, since there are patient groups with clear symptomatic, course and biomarker differences. SZ is characterized by a hyperdopaminergic state related to high dopamine D2 receptor activity. It has also been proposed that there is a hypoadenosynergic state. Adenosine is a nucleoside widely distributed in the organism with neuromodulative and neuroprotective activity in the central nervous system. In the brain, the most abundant adenosine receptors are A1R and A2AR. In the present report, we characterize the presence of both receptors in human postmortem putamens of patients suffering SZ with real time TaqMan PCR, western blotting and radioligand binding assay. We show that A1R levels remain unchanged with respect to age-matched controls, whereas nearly fifty percent of patients have reduced A2AR, at the transcriptional and translational levels. Moreover, we describe how DNA methylation plays a role in the pathological A2AR levels with the bisulfite-sequencing technique. In fact, an increase in 5-methylcytosine percentage in the 5' UTR region of ADORA2A was found in those SZ patients with reduced A2AR levels. Interestingly, there was a relationship between the A2A/β-actin ratio and motor disturbances as assessed with some items of the PANSS, AIMS and SAS scales. Therefore, there may be a subgroup of SZ patients with reduced striatal A2AR levels accompanied by an altered motor phenotype. PMID:24433848

  8. Disruption of adenosine-5'-phosphosulfate kinase in Arabidopsis reduces levels of sulfated secondary metabolites.

    PubMed

    Mugford, Sarah G; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-03-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5'-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3'-phosphoadenosine 5'-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  9. 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

  10. 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.

  11. The awareness level and needs for education on reducing sugar consumption among mothers with preschool children

    PubMed Central

    Lee, Younhee

    2016-01-01

    BACKGROUND/OBJECTIVES The purpose of this study was to find out the level of knowledge on sugar-related nutrition among mothers with preschool children. SUBJECTS/METHODS The study conducted a survey on 350 mothers whose children attended daycare. The dietary lives of the children and the nutritional knowledge of the mothers on sugar were checked. In order to analyze results, SPSS 18.0 was used. ANOVA and t-test were also performed to analyze recognition and educational needs. RESULTS When the degree of nutritional knowledge was measured and analyzed, the results showed about 11 average points out of 15. The higher a group's nutritional knowledge, the better the dietary habits and activities were and the activities were more ccommon. The group with a low level of nutritional knowledge consumed more foods with high sugar content, but this difference was not statistically significant. Also the children from the group of mothers that provided nutritional education to their children were more likely to engage in better dietary habits and activities. CONCLUSIONS 66.5% respondents did not know about policies to reduce sugar consumption, but most indicated that education on reducing sugar consumption is needed. Therefore, a government-driven search for efficient methods to campaign and publicize sugar reduction is needed in order to continuously provide appropriate education. PMID:27087908

  12. 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.

  13. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure

    PubMed Central

    Miranda da Silva, Cristiane; Peres Leal, Mayara; Brochetti, Robson Alexandre; Braga, Tárcio; Vitoretti, Luana Beatriz; Saraiva Câmara, Niels Olsen; Damazo, Amílcar Sabino; Ligeiro-de-Oliveira, Ana Paula; Chavantes, Maria Cristina; Lino-dos-Santos-Franco, Adriana

    2015-01-01

    Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant. PMID:26569396

  14. 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,…

  15. 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

  16. 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

  17. 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.

  18. Are Preschool Children Active Enough? Objectively Measured Physical Activity Levels

    ERIC Educational Resources Information Center

    Cardon, Greet M.; De Bourdeaudhuij, Ilse M. M.

    2008-01-01

    The present study aimed to describe accelerometer-based physical activity levels in 4- and 5-year-old children (N = 76) on 2 weekdays and 2 weekend days. The children were sedentary for 9.6 hr (85%) daily, while they engaged in moderate to vigorous physical activity (MVPA) for 34 min (5%). Only 7% of the children engaged in MVPA for 60 min per…

  19. Sesamol treatment reduces plasma cholesterol and triacylglycerol levels in mouse models of acute and chronic hyperlipidemia.

    PubMed

    Kumar, Nitesh; Mudgal, Jayesh; Parihar, Vipan K; Nayak, Pawan G; Kutty, N Gopalan; Rao, C Mallikarjuna

    2013-06-01

    The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200 mg/kg) significantly (P < 0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200 mg/kg was equivalent to 10 mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200 mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24 h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2 % w/w), cholic acid (1 % w/w) and coconut oil 30 % (v/w) with standard powdered standard animal chow (up to 100 g). Niacin (100 mg/kg) and sesamol (100 mg/kg) significantly (P < 0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P < 0.05) reversed by the sesamol (50 and 100 mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well. PMID:23504268

  20. Antagonism of P2Y₁₂ reduces physiological thromboxane levels.

    PubMed

    Bhavaraju, Kamala; Georgakis, Alexander; Jin, Jianguo; Gartner, Theodore Kent; Tomiyama, Yoshiaki; Nurden, Alan; Nurden, Paquita; Kunapuli, Satya P

    2010-01-01

    Antiplatelet therapy for the management of patients with cardiovascular risks often includes a combination therapy of aspirin and clopidogrel, acting through inhibition of thromboxane generation and blockade of G(i)-coupled P2Y₁₂ receptor, respectively. We hypothesized that ADP acting through P2Y₁₂ regulates physiological thromboxane levels. The serum thromboxane levels in mice (n = 3) dosed with clopidogrel and prasugrel were decreased by 83.1 ± 5.3% and 94.26 ± 1.75% respectively compared to untreated mice. Pre-treatment of human blood (n = 3) ex vivo with active metabolites of clopidogrel or prasugrel led to a reduction in thromboxane levels to 16.3 ± 3.2% and 4.9 ± 0.8% respectively, compared to untreated human serum. We also evaluated serum thromboxane levels in P2Y receptor null mice (n = 4). Whereas serum thromboxane levels in P2Y₁ null mice were similar to those in wild type littermates, those in the P2Y₁₂ null mice were inhibited by 83.15 ± 3.8%. Finally, in a pilot study, serum thromboxane levels were reduced by 76.05 ± 8.41% in healthy human volunteers (n = 6) upon dosing with clopidogrel, compared to the levels before dosing. In conclusion, P2Y₁₂ antagonism alone can decrease physiological thromboxane levels. Thus, this study could pave way the for newer/modified treatment regimens for the management of patients with thrombotic complications who are allergic or non-responsive to aspirin. PMID:21067313

  1. CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice.

    PubMed

    Wolf, Risa M; Lei, Xia; Yang, Zhi-Chun; Nyandjo, Maeva; Tan, Stefanie Y; Wong, G William

    2016-03-01

    C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity. PMID:26670485

  2. 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.

  3. 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

  4. 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.

  5. Itching, pain, and anxiety levels are reduced with massage therapy in burned adolescents.

    PubMed

    Parlak Gürol, Ayşe; Polat, Sevinç; Akçay, Müfide Nuran

    2010-01-01

    Burn can be among the most severe physical and psychologic traumas a person may face. Patients with burns commonly have severe itching and pain. Severe itching has also been associated with anxiety, sleep disturbance, and disruption of daily living activities. The addition of complementary treatments to standard care may lead to improved pain management and may offer a safer approach for reducing pain and procedural anxiety for patients with burns. The authors conducted an experimental study to examine whether the effects of massage therapy reduced burned adolescents' pain, itching, and anxiety levels. Sixty-three adolescents were enrolled in this study shortly after admission (mean days = 3 +/- 0.48) at a burn unit in a large university hospital from February 2008 to June 2009. The measures including the pain, itching, and state anxiety were collected on the first and last days of the 5-week study period. The participants had an average age of 14.07 +/- 1.78 years and came usually from the lower socioeconomic strata. The authors observed that massage therapy reduced all these measures from the first to the last day of this study (P < .001). In most cultures, massage treatments are used to alleviate a wide range of symptoms. Although health professionals agree on the use of nonpharmacologic method for patients with burns, these applications are not yet common. PMID:20453734

  6. 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

  7. 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

  8. Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells

    PubMed Central

    Han, Ihn; Jung, Ji Hoon; Lee, Eun-Ok; Zhu, Shudong; Chen, Chang-Yan; Kim, Sung-Hoon

    2010-01-01

    Background We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. Methodology/Principal Findings We showed that PO (IC50  = 17.3 µg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC50 over 200 µg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 µg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 µg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. Conclusions/Significance Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells. PMID:20808805

  9. 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

  10. Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows

    PubMed Central

    Noyes, Pamela D.; Lema, Sean C.; Macaulay, Laura J.; Douglas, Nora K.; Stapleton, Heather M.

    2013-01-01

    Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (~3 ng/g bw-day) and high dose (~300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3'-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ~65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting non-linear relationships between BDE-209 exposures and thyroid dysfunction. PMID:23899252

  11. A School-Level Proxy Measure for Individual-level Poverty Using School-Level Eligibility for Free and Reduced-Price Meals

    ERIC Educational Resources Information Center

    Day, Sophia E.; Hinterland, Kinjia; Myers, Christa; Gupta, Leena; Harris, Tiffany G.; Konty, Kevin J.

    2016-01-01

    Background: Socioeconomic status (SES) impacts health outcomes. The Youth Risk Behavior Survey (YRBS), like many school-based data sources, lacks individual-level poverty information. We propose using school-level percentages of student eligibility for free/reduced-price meals (%FRPM) as a proxy for individual-level poverty. Methods: Using the New…

  12. 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

  13. Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats

    PubMed Central

    Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu

    2016-01-01

    Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP

  14. Reduced progesterone levels explain the reduced risk of breast cancer in obese premenopausal women: a new hypothesis.

    PubMed

    Dowsett, Mitch; Folkerd, Elizabeth

    2015-01-01

    Understanding the complex relationship between obesity and breast cancer is fundamental to our knowledge of the etiology of this malignancy; changes in the composition of the hormonal milieu are implicit in this process. Estrogens are synthesized from androgens by aromatase in the gonads and in peripheral tissues, principally, adipose tissue. Obesity in women, regardless of their age, leads to more aromatase and more extra-glandular estrogen production. In postmenopausal women, in whom ovarian estrogen production is absent, the increased incidence of breast cancer in women with high body mass index has been attributed to the relatively high plasma levels of estradiol from subcutaneous fat. In contrast, obesity in premenopausal women is associated with a previously unexplained reduced incidence of breast cancer. In obese premenopausal women, the cumulative effect of higher levels of estrogens synthesized in the peripheral tissues, together with ovarian estrogen production, results in a negative feedback on the hypothalamic pituitary controlled release of gonadotrophins and a resultant diminution in ovarian steroid production. As a consequence, the normal balance of estrogen and progesterone levels is disrupted: while estrogen levels are normalized, progesterone production is markedly decreased. Progesterone is a promoter of proliferation in the breast. The low levels of progesterone in obese premenopausal women are consistent with, and we propose, are responsible for, the reduction in breast cancer incidence in these women. PMID:25414027

  15. Nestling activity levels during begging behaviour predicts activity level and body mass in adulthood

    PubMed Central

    Griffith, Simon C.

    2014-01-01

    Across a range of species including humans, personality traits, or differences in behaviour between individuals that are consistent over time, have been demonstrated. However, few studies have measured whether these consistent differences are evident in very young animals, and whether they persist over an individual’s entire lifespan. Here we investigated the begging behaviour of very young cross-fostered zebra finch nestlings and the relationship between that and adult activity levels. We found a link between the nestling activity behaviour head movements during begging, measured at just five and seven days after hatching, and adult activity levels, measured when individuals were between three and three and a half years old. Moreover, body mass was found to be negatively correlated with both nestling and adult activity levels, suggesting that individuals which carry less body fat as adults are less active both as adults and during begging as nestlings. Our work suggests that the personality traits identified here in both very young nestlings and adults may be linked to physiological factors such as metabolism or environmental sources of variation. Moreover, our work suggests it may be possible to predict an individual’s future adult personality at a very young age, opening up new avenues for future work to explore the relationship between personality and a number of aspects of individual life history and survival. PMID:25279258

  16. Nestling activity levels during begging behaviour predicts activity level and body mass in adulthood.

    PubMed

    McCowan, Luke S C; Griffith, Simon C

    2014-01-01

    Across a range of species including humans, personality traits, or differences in behaviour between individuals that are consistent over time, have been demonstrated. However, few studies have measured whether these consistent differences are evident in very young animals, and whether they persist over an individual's entire lifespan. Here we investigated the begging behaviour of very young cross-fostered zebra finch nestlings and the relationship between that and adult activity levels. We found a link between the nestling activity behaviour head movements during begging, measured at just five and seven days after hatching, and adult activity levels, measured when individuals were between three and three and a half years old. Moreover, body mass was found to be negatively correlated with both nestling and adult activity levels, suggesting that individuals which carry less body fat as adults are less active both as adults and during begging as nestlings. Our work suggests that the personality traits identified here in both very young nestlings and adults may be linked to physiological factors such as metabolism or environmental sources of variation. Moreover, our work suggests it may be possible to predict an individual's future adult personality at a very young age, opening up new avenues for future work to explore the relationship between personality and a number of aspects of individual life history and survival. PMID:25279258

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52

    NASA Astrophysics Data System (ADS)

    Jo, Chulman; Gundemir, Soner; Pritchard, Susanne; Jin, Youngnam N.; Rahman, Irfan; Johnson, Gail V. W.

    2014-03-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo.

  4. 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

  5. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  6. Determinants affecting physical activity levels in animal models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C L.; Wade, Charles E.

    2002-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  7. Determinants Affecting Physical Activity Levels In Animal Models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C. L.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  8. Tension between reducing sea-level rise and global warming through solar-radiation management

    NASA Astrophysics Data System (ADS)

    Irvine, P. J.; Sriver, R. L.; Keller, K.

    2012-02-01

    Geoengineering using solar-radiation management (SRM) is gaining interest as a potential strategy to reduce future climate change impacts. Basic physics and past observations suggest that reducing insolation will, on average, cool the Earth. It is uncertain, however, whether SRM can reduce climate change stressors such as sea-level rise or rates of surface air temperature change. Here we use an Earth system model of intermediate complexity to quantify the possible response of sea levels and surface air temperatures to projected climate forcings and SRM strategies. We find that SRM strategies introduce a potentially strong tension between the objectives to reduce (1) the rate of temperature change and (2) sea-level rise. This tension arises primarily because surface air temperatures respond faster to radiative forcings than sea levels. Our results show that the forcing required to stop sea-level rise could cause a rapid cooling with a rate similar to the peak business-as-usual warming rate. Furthermore, termination of SRM was found to produce warming rates up to five times greater than the maximum rates under the business-as-usual CO2 scenario, whereas sea-level rise rates were only 30% higher. Reducing these risks requires a slow phase-out of many decades and thus commits future generations.

  9. 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

  10. 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

  11. 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

  12. 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

  13. Reduced Levels of Membrane-Bound Alkaline Phosphatase Are Common to Lepidopteran Strains Resistant to Cry Toxins from Bacillus thuringiensis

    PubMed Central

    Jurat-Fuentes, Juan Luis; Karumbaiah, Lohitash; Jakka, Siva Rama Krishna; Ning, Changming; Liu, Chenxi; Wu, Kongming; Jackson, Jerreme; Gould, Fred; Blanco, Carlos; Portilla, Maribel; Perera, Omaththage; Adang, Michael

    2011-01-01

    Development of insect resistance is one of the main concerns with the use of transgenic crops expressing Cry toxins from the bacterium Bacillus thuringiensis. Identification of biomarkers would assist in the development of sensitive DNA-based methods to monitor evolution of resistance to Bt toxins in natural populations. We report on the proteomic and genomic detection of reduced levels of midgut membrane-bound alkaline phosphatase (mALP) as a common feature in strains of Cry-resistant Heliothis virescens, Helicoverpa armigera and Spodoptera frugiperda when compared to susceptible larvae. Reduced levels of H. virescens mALP protein (HvmALP) were detected by two dimensional differential in-gel electrophoresis (2D-DIGE) analysis in Cry-resistant compared to susceptible larvae, further supported by alkaline phosphatase activity assays and Western blotting. Through quantitative real-time polymerase chain reaction (qRT-PCR) we demonstrate that the reduction in HvmALP protein levels in resistant larvae are the result of reduced transcript amounts. Similar reductions in ALP activity and mALP transcript levels were also detected for a Cry1Ac-resistant strain of H. armigera and field-derived strains of S. frugiperda resistant to Cry1Fa. Considering the unique resistance and cross-resistance phenotypes of the insect strains used in this work, our data suggest that reduced mALP expression should be targeted for development of effective biomarkers for resistance to Cry toxins in lepidopteran pests. PMID:21390253

  14. Highly charged swelling mica reduces free and extractable Cu levels in Cu-contaminated soils.

    PubMed

    Stuckey, Jason W; Neaman, Alexander; Ravella, Ramesh; Komarneni, Sridhar; Martínez, Carmen Enid

    2008-12-15

    Smelting of copper (Cu) results in the atmospheric deposition of Cu onto surrounding soils. Excess concentrations of Cu in soils can be absorbed by soil biota to toxic levels or leached into the groundwater, threatening the entire ecosystem. A means to restrict Cu mobility and uptake by plants is to remove it from the aqueous phase by applying an adsorptive material. A synthetic clay (highly charged swelling mica) was tested for its ability to decrease the levels of free and 0.1 M KNO3-extractable Cu in 15 surface soils from three different Cu mining areas in central Chile. The soils contained excessive total Cu levels (112-2790 mg Cu (kg soil)(-1)), while extractable Cu ranged from 0.3 to 22.9 mg Cu L(-1). The mica was applied to each soil at rates of 0.1%, 1%, and 2% (w/w). A 2% sodium-montmorillonite treatment and the nonamended soil served as controls. The order of treatment efficacy in reducing extractable Cu and free Cu2+ for low pH soils ( 1% mica > 2% montmorillonite > 0.1% mica. At 120 days, the 2% mica treatment maintained reductions of up to 93% in the free Cu2+ activity and up to 75% in the extractable Cu concentration upon acidification to the original soil pH value. In addition, Cu retention in mica-treated soils was more resistant to acidification than in lime-treated soils. This mica has promise for the remediation of acidic soils with metal contamination at the surface. PMID:19174892

  15. 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

  16. Job level risk assessment using task level ACGIH hand activity level TLV scores: a pilot study.

    PubMed

    Drinkaus, Phillip; Sesek, Richard; Bloswick, Donald S; Mann, Clay; Bernard, Thomas

    2005-01-01

    Existing upper extremity musculoskeletal disorder analytical tools are primarily intended for single or mono-task jobs. However, many jobs contain more than 1 task and some include job rotation. This case/control study investigates methods of modifying an existing tool, the American Conference of Governmental Industrial Hygienists (ACGIH) Hand Activity Level (HAL) Threshold Limit Value (TLV), to assess the upper extremity risk of multi-task jobs. Various methods of combining the task differences and ratios into a job level assessment were explored. Two methods returned significant odds ratios, (p < .05) of 18.0 (95% CI 1.8-172) and 12.0 (95% CI 1.2-120). These results indicate that a modified ACGIH HAL TLV may provide insight into the work-related risk of multi-task jobs. Further research is needed to optimize this process. PMID:16219155

  17. 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

  18. 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

  19. 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

  20. Developing Community-Level Policy and Practice to Reduce Traffic-Related Air Pollution Exposure

    PubMed Central

    Brugge, Doug; Patton, Allison P.; Bob, Alex; Reisner, Ellin; Lowe, Lydia; Bright, Oliver-John M.; Durant, John L.; Newman, Jim; Zamore, Wig

    2016-01-01

    The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic-related pollutants (TRAP) are elevated within 200–400 m of these roads. Community-level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near-highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning. PMID:27413416

  1. Bird activity levels related to weather

    USGS Publications Warehouse

    Robbins, C.S.

    1981-01-01

    The Breeding Bird Survey data bank serves as a primary source for studying effects of sky cover, wind speed, and temperature on bird census results. Other standardized methods, such as spot-mapping (Breeding Bird Census), point counts, banding, and the Winter Bird Survey, provide additional, but limited, means of assessing effects of weather. Numbers of songbirds detected are generally inversely correlated with wind speed, but hawks often are seen in larger numbers on windy days. Rain greatly reduces the numbers of birds detected. Cloud cover has relatively little influence on early morning bird counts during the peak of the breeding season. Fog selectively favors auditory detections of some species. Counts of many species are correlated with temperature, but effects are minor unless temperatures are extreme. Under marginal weather conditions, total species observed may be nearly normal, whereas number of individuals observed is reduced, as is the opportunity to record simultaneous registrations

  2. Activity-dependent regulation of astrocyte GAT levels during synaptogenesis

    PubMed Central

    Muthukumar, Allie K.; Stork, Tobias; Freeman, Marc R.

    2014-01-01

    Astrocytic uptake of GABA through GABA transporters (GATs) is an important mechanism regulating excitatory/inhibitory balance in the nervous system, however mechanisms by which astrocytes regulate GAT levels are undefined. Here we show at mid-pupal stages the Drosophila CNS neuropil is devoid of astrocyte membranes and synapses. Astrocyte membranes subsequently infiltrate the neuropil coordinate with synaptogenesis and a strocyte ablation reduces synapse numbers by half, indicating that Drosophila astrocytes are pro-synaptogenic. Shortly after synapses form in earnest, the GABA transporter, GAT, is up-regulated in astrocytes. Ablation or silencing of GABAergic neurons or disruption of metabotropic GABA receptor (GABABR1/2) signaling in astrocytes leads to decreased astrocytic GAT levels. Interestingly, developmental depletion of astrocytic GABABR1/2 signaling suppresses mechanosensory-induced seizure activity in mutants with hyperexcitable neurons. These data reveal astrocytes actively modulate GAT expression via metabotropic GABA receptor signaling, and highlight the importance of precise regulation of astrocytic GAT in modulation of seizure activity. PMID:25151265

  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. 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.

  5. Entry-Level Activities in System Consultation

    ERIC Educational Resources Information Center

    Hylander, Ingrid

    2014-01-01

    System-level consultation or organizational development in schools is an area in great need of theoretical models and definitions. The three articles in this special issue provide a unique learning opportunity not only for consultation across borders but also for consultation within the same nation. In my commentary, I limit my remarks to a few…

  6. Hardee County Energy Activities - Middle School Level.

    ERIC Educational Resources Information Center

    Allen, Rodney F., Ed.

    Described are over 70 activities designed to help students develop writing skills by examining energy issues. Intended for middle school students, the lessons were developed by Hardee County, Florida teachers. Learning strategies employed include class discussions, analogies, word puzzles, letter writing, sentence completions, vocabulary building…

  7. Human Development Program: Level VI Activity Guide.

    ERIC Educational Resources Information Center

    Ball, Geraldine

    The curriculum guide presents the activities component of the Human Development Program for grade 6. The Human Development Program (HDP) is an affective curricular approach developed by psychologists to aid teachers in instilling responsibility and self-confidence in children. The nucleus of the Human Development Program is a circle session…

  8. Human Development Program: Level III Activity Guide.

    ERIC Educational Resources Information Center

    Bessell, Harold

    The curriculum guide presents the activities component of the Human Development Program for the third grade. The Human Development Program (HDP) is an affective curricular approach developed by psychologists to help teachers instill responsibility and self-confidence in children. Following a brief overview of the HDP and explanation of the Magic…

  9. 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

  10. An Action Science Research Approach to Reducing Student Tardiness at the High School Level

    ERIC Educational Resources Information Center

    Gile, Curtis S.

    2013-01-01

    The purpose of this action research study was to design, implement, analyze, and evaluate a series of interventions to reduce student tardiness at the high school level. Another purpose of the study was to determine the underlying values, beliefs, and behaviors associated with student tardiness from a faculty and staff perspective. The study…

  11. PROLONGED FASTING AND CORTISOL REDUCE MYOSTATIN MRNA LEVELS IN TILAPIA LARVAE, SHORT-TERM FASTING ELEVATES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indices in adults, skeletal muscle myostatin mRNA...

  12. Schoolwide Intervention to Reduce Chronic Tardiness at the Middle and High School Levels

    ERIC Educational Resources Information Center

    Tyre, Ashli; Feuerborn, Laura; Pierce, Jennifer

    2011-01-01

    When many students are tardy at the secondary level, teachers must continually restart instruction or delay beginning instructional periods throughout the school day. To address the considerable amount of instructional time lost caused by high rates of tardiness, the authors investigated the results of schoolwide intervention to reduce student…

  13. An element in the bovine papillomavirus late 3' untranslated region reduces polyadenylated cytoplasmic RNA levels.

    PubMed

    Furth, P A; Baker, C C

    1991-11-01

    Expression of the two bovine papillomavirus type 1 (BPV-1) late genes, L1 and L2, coding for the two capsid proteins, is limited to terminally differentiated keratinocytes in bovine fibropapillomas. This pattern of expression is determined both by the activity of the late promoter and by the inhibition of late region expression in less well differentiated cells. Inhibition of L1 and L2 mRNA production in nonpermissive cells must occur since the late region potentially could be transcribed from early region promoters. Nuclear runoff analysis of the late region has demonstrated that up to 95% of transcripts which are initiated in the early region in nonpermissive cells terminate within the late region upstream of the late polyadenylation site (C. C. Baker and J. Noe, J. Virol. 63:3529-3534, 1989). However, very few of the primary transcripts which include the late polyadenylation site are processed into mRNA. In this study, we have used expression vectors to characterize an inhibitory element active in nonpermissive cells which is located in the late 3' untranslated region (3'UTR). While the late polyadenylation site is functional in these cells, a 53-bp element in the late 3'UTR reduces levels of polyadenylated cytoplasmic RNA. This element inhibited chloramphenicol acetyltransferase (CAT) expression 6- to 10-fold when cloned in the sense orientation into the 3'UTR of a CAT expression vector. No block to expression was seen when the fragment was cloned immediately downstream of the poly(A) site, in an intron upstream of the CAT coding sequence, or in an antisense orientation in the 3'UTR. When the same fragment was deleted from a BPV-1 L1 expression vector, a sixfold increase in mRNA levels was seen. Actinomycin D chase experiments using BPV-1 L1 expression vectors indicated that the element does not destabilize cytoplasmic polyadenylated RNA. Therefore, the element must act before the mature mRNA reaches the cytoplasm. The data presented are consistent with effects

  14. 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

  15. 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

  16. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway.

    PubMed

    Sun, Li; Zhang, Song; Yu, Chengyuan; Pan, Zhenwei; Liu, Yang; Zhao, Jing; Wang, Xiaoyu; Yun, Fengxiang; Zhao, Hongwei; Yan, Sen; Yuan, Yue; Wang, Dingyu; Ding, Xue; Liu, Guangzhong; Li, Wenpeng; Zhao, Xuezhu; Liu, Zhaorui; Li, Yue

    2015-12-01

    Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2(-/-) mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway. PMID:26442880

  17. 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

  18. 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

  19. Reduced serum levels of 1 alpha,25-dihydroxyvitamin D during long-term total parenteral nutrition.

    PubMed

    Klein, G L; Horst, R L; Norman, A W; Ament, M E; Slatopolsky, E; Coburn, J W

    1981-05-01

    Painful bone disease, characterized by patchy osteomalacia and inactive bone, can develop in patients treated with total parenteral nutrition for more than 3 months. Serum levels of 1 alpha,25-dihydroxyvitamin D (1 alpha, 25(OH)2D), 24,25-dihydroxyvitamin D and 25-hydroxyvitamin D were measured in seven adults and five children treated with parenteral nutrition for 9 to 60 months. Serum levels of 1 alpha, 25(OH)2D were markedly reduced, while levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were normal. Serum calcium and phosphorus levels were normal or slightly increased, and immunoreactive parathyroid hormone levels were normal or low. Renal function was normal or minimally reduced. Skeletal symptoms disappeared and serum 1 alpha, 25(OH)2D levels rose to normal in one patient when nutrient infusions were discontinued for 6 weeks. Removal of calcium from the nutrient solution for 2 to 4 days was associated with no change in serum 1 alpha, 25(OH)2D in two patients. The cause of the reduction in serum levels of 1 alpha, 25(OH)2D and its role in the pathogenesis of bone disease in these patients remain uncertain. PMID:6786151

  20. Directly Observed Physical Activity Levels in Preschool Children

    ERIC Educational Resources Information Center

    Pate, Russell R.; McIver, Kerry; Dowda, Marsha; Brown, William H.; Addy, Cheryl

    2008-01-01

    Background: Millions of young children attend preschools and other structured child development programs, but little is known about their physical activity levels while in those settings. The purpose of this study was to describe the physical activity levels and demographic and school-related correlates of physical activity in children attending…

  1. Antisense RNA Inhibition of RbcS Gene Expression Reduces Rubisco Level and Photosynthesis in the C4 Plant Flaveria bidentis.

    PubMed

    Furbank, R. T.; Chitty, J. A.; Von Caemmerer, S.; Jenkins, CLD.

    1996-07-01

    The C4 dicot Flaveria bidentis was genetically transformed with an antisense RNA construct targeted to the nuclear-encoded gene for the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; RbcS). RbcS mRNA levels in leaves of transformants were reduced by as much as 80% compared to wild-type levels, and extractable enzyme activity was reduced by up to 85%. There was no significant effect of transformation with the gene construct on levels of other photosynthetic enzymes. Antisense transformants with reduced Rubisco activity exhibited a stunted phenotype. Rates of photosynthesis were reduced in air at high light and over a range of CO2 concentrations but were unaffected at low light. From these results we conclude that, as is the case in C3 plants, Rubisco activity is a major determinant of photosynthetic flux in C4 plants under high light intensities and air levels of CO2. PMID:12226324

  2. Increasing the maximally random jammed density with electric field to reduce the fat level in chocolate

    NASA Astrophysics Data System (ADS)

    Tao, R.; Tang, H.

    Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. For example, a typical molding chocolate has various fat up to 40% in total and chocolate for covering ice cream has fat 50 -60%. Especially, as children are the leading chocolate consumers, reducing the fat level in chocolate products to make them healthier is important and urgent. While this issue was called into attention and elaborated in articles and books decades ago and led to some patent applications, no actual solution was found unfortunately. Why is reducing fat in chocolate so difficult? What is the underlying physical mechanism? We have found that this issue is deeply related to the basic science of soft matters, especially to their viscosity and maximally random jammed (MRJ) density φx. All chocolate productions are handling liquid chocolate, a suspension with cocoa solid particles in melted fat, mainly cocoa butter. The fat level cannot be lower than 1-φxin order to have liquid chocolate to flow. Here we show that that with application of an electric field to liquid chocolate, we can aggregate the suspended particles into prolate spheroids. This microstructure change reduces liquid chocolate's viscosity along the flow direction and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are looking forward to a new class of healthier and tasteful chocolate coming to the market soon. Dept. of Physics, Temple Univ, Philadelphia, PA 19122.

  3. 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

  4. Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

    PubMed

    Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

    2014-12-01

    Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. PMID:25445987

  5. 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

  6. Obstructive Sleep Apnea and Obesity are Associated With Reduced GPR 120 Plasma Levels in Children

    PubMed Central

    Gozal, David; Kheirandish-Gozal, Leila; Carreras, Alba; Khalyfa, Abdelnaby; Peris, Eduard

    2014-01-01

    Background: Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promotes increased food intake. G protein-coupled receptor 120 (GPR 120) is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects against insulin resistance and systemic inflammation. We hypothesized that GPR 120 levels would be reduced in children with OSA, particularly among obese children. Study Design: Cross-sectional prospectively recruited cohort. Setting: Academic pediatric sleep program. Methods: Two hundred twenty-six children (mean age: 7.0 ± 2.1 y) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP) assays, monocyte GPR 120 expression, and plasma GPR 120 levels were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay kits. Results: Obese children and those with OSA had significantly lower GPR 120 monocyte expression and plasma GPR 120 levels. Furthermore, when both obesity and OSA were present, GPR 120 levels were lowest. Linear associations emerged between GPR 120 plasma levels and body mass index (BMI) z score, as well as with apnea-hypopnea index (AHI), saturation of peripheral oxygen (SpO2) nadir, and respiratory arousal index (RAI), with RAI remaining statistically significant when controlling for age, ethnicity, sex, and BMI z score (P < 0.001). Similarly, HOMA-IR was significantly associated with GPR 120 levels, but neither low density lipoprotein nor high density lipoprotein cholesterol or hsCRP levels exhibited significant correlations. Conclusions: G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric OSA and obesity (particularly when both are present) and may play a role in

  7. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men

    PubMed Central

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  8. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men.

    PubMed

    Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m², age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  9. Reducing bullying and victimization: student- and classroom-level mechanisms of change.

    PubMed

    Saarento, Silja; Boulton, Aaron J; Salmivalli, Christina

    2015-01-01

    This longitudinal study examines the mediating mechanisms by which the KiVa antibullying program, based on the Participant Role approach, reduces bullying and victimization among elementary school students. Both student-level mechanisms leading to reduced perpetration of bullying and classroom-level mechanisms leading to reductions in bullying and victimization are considered. Analyses are based on a sample of 7,491 students (49.5% boys) nested within 421 classrooms within 77 schools. At the beginning of program implementation, the children were in Grades 4, 5, and 6 (mean age 11.3 years). Multilevel structural equation modeling was used to analyze whether changes in the hypothesized mediators accounted for later reductions in the outcomes. At the student level, antibullying attitudes and perceptions regarding peers' defending behaviors and teacher attitudes toward bullying mediated the effects of KiVa on self-reported bullying perpetration. The effects on peer-reported bullying were only mediated by antibullying attitudes. At the classroom level, the program effects on both self- and peer-reported bullying were mediated by students' collective perceptions of teacher attitudes toward bullying. Also, perceived reinforcing behaviors predicted bullying but did not emerge as a significant mediator. Finally, bullying mediated the effects of the classroom-level factors on victimization. These findings enhance knowledge of the psychosocial developmental processes contributing to bullying and victimization and shed light on the key mechanisms by which school bullying can successfully be counteracted. PMID:24390403

  10. High intensity and reduced volume training attenuates stress and recovery levels in elite swimmers.

    PubMed

    Elbe, Anne-Marie; Rasmussen, Camilla P; Nielsen, Glen; Nordsborg, Nikolai B

    2016-04-01

    This study investigated the effect of increased high-intensity interval training (HIT) at the expense of total training volume on the stress and recovery levels of elite swimmers. Forty-one elite swimmers participated in the study and were randomly assigned to either a HIT or a control group (CON). Eleven swimmers did not complete the questionnaires. For 12 weeks both groups trained ~12 h per week. The amount of HIT was ~5 h vs. 1 h, and total distance was ~17 km vs. ~35 km per week for HIT and CON, respectively. HIT was performed as 6-10 × 10-30 s maximal effort interspersed by 2-4 min of rest. The Recovery Stress Questionnaire - Sport was used to measure the swimmers' stress and recovery levels. After the 12 week intervention, the general stress level was 16.6% (2.6-30.7%; mean and 95% CI) lower and the general recovery level was 6.5% (0.7-12.4%) higher in HIT compared to the CON, after adjusting for baseline values. No significant effects could be observed in sports-specific stress or sports-specific recovery. The results indicate that increasing training intensity and reducing training volume for 12 weeks can reduce general stress and increase general recovery levels in competitive swimmers. PMID:25867005

  11. Ascorbic acid serum levels are reduced in patients with hematological malignancies

    PubMed Central

    Huijskens, Mirelle J.A.J.; Wodzig, Will K.W.H.; Walczak, Mateusz; Germeraad, Wilfred T.V.; Bos, Gerard M.J.

    2016-01-01

    In this paper we demonstrate that patients treated with chemotherapy and/or hematopoietic stem cell transplantation (HSCT) have highly significant reduced serum ascorbic acid (AA) levels compared to healthy controls. We recently observed in in vitro experiments that growth of both T and NK cells from hematopoietic stem cells is positively influenced by AA. It might be of clinical relevance to study the function and recovery of immune cells after intensive treatment, its correlation to AA serum levels and the possible effect of AA supplementation. PMID:27014565

  12. 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

  13. 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

  14. Activity profile of high-level Australian lacrosse players.

    PubMed

    Polley, Chris S; Cormack, Stuart J; Gabbett, Tim J; Polglaze, Ted

    2015-01-01

    Despite lacrosse being one of the fastest growing team sports in the world, there is a paucity of information detailing the activity profile of high-level players. Microtechnology systems (global positioning systems and accelerometers) provide the opportunity to obtain detailed information on the activity profile in lacrosse. Therefore, this study aimed to analyze the activity profile of lacrosse match-play using microtechnology. Activity profile variables assessed relative to minutes of playing time included relative distance (meter per minute), distance spent standing (0-0.1 m·min), walking (0.2-1.7 m·min), jogging (1.8-3.2 m·min), running (3.3-5.6 m·min), sprinting (≥5.7 m·min), number of high, moderate, low accelerations and decelerations, and player load (PL per minute), calculated as the square root of the sum of the squared instantaneous rate of change in acceleration in 3 vectors (medio-lateral, anterior-posterior, and vertical). Activity was recorded from 14 lacrosse players over 4 matches during a national tournament. Players were separated into positions of attack, midfield, or defense. Differences (effect size [ES] ± 90% confidence interval) between positions and periods of play were considered likely positive when there was ≥75% likelihood of the difference exceeding an ES threshold of 0.2. Midfielders had likely covered higher (mean ± SD) meters per minute (100 ± 11) compared with attackers (87 ± 14; ES = 0.89 ± 1.04) and defenders (79 ± 14; ES = 1.54 ± 0.94) and more moderate and high accelerations and decelerations. Almost all variables across positions were reduced in quarter 4 compared with quarter 1. Coaches should accommodate for positional differences when preparing lacrosse players for competition. PMID:25264672

  15. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    PubMed Central

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane. PMID:27306853

  16. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels.

    PubMed

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K(+) and Na(+) by three orders of magnitude compared to the GO membrane. PMID:27306853

  17. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    NASA Astrophysics Data System (ADS)

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-06-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane.

  18. Effects of carvedilol reduce conjunctivitis through changes in inflammation, NGF and VEGF levels in a rat model

    PubMed Central

    CHEN, YING; HONG, XIANFEI

    2016-01-01

    Carvedilol is a novel third generation β-blocker that acts as an antagonist of β and α adrenergic receptors, and is able to regulate various cell factors. In addition, it possesses antioxidant activity, is capable of reversing cardiac remodeling effects and has anti-arrhythmic effects. The present study aimed to investigate whether the effects of carvedilol were able to reduce conjunctivitis clinical scores. Initially, 24 Sprague Dawley (SD) rats were randomly divided into three equal groups as follows: Control group, model group and carvedilol group. The model and carvedilol group adult SD rats were injected with lipopolysaccharide (LPS) to induce conjunctivitis. In the carvedilol group, the eight SD rats with LPS-induced conjunctivitis also received 50 mg/kg/day of carvedilol for 4 weeks. Next, the effects carvedilol were assessed utilizing a system of clinical sign scores, and an enzyme-linked immunosorbent assay was used to determine the expression levels of interleukin-1β (IL-1β), IL-6, IL-8 and tumor necrosis factor-α (TNF-α). Finally, nuclear factor-κB (NF-κB), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were analyzed by western blotting. Carvedilol was observed to significantly reduce clinical sign scores in a dose-dependent manner (P<0.01), and reduce IL-1β, IL-6, IL-8 and TNF-α expression levels (P<0.01) in the LPS-induced rat model of conjunctivitis. Carvedilol was also able to significantly reduce the protein expression levels of NF-κB, and induce the protein expression levels of NGF and VEGF in the LPS-induced rat model of conjunctivitis (P<0.01). In conclusion, the effects of carvedilol may reduce conjunctivitis clinical scores through inflammation, NGF and VEGF in LPS-induced rat models. PMID:27168839

  19. Circulating Heat Shock Protein 60 Levels Are Elevated in HIV Patients and Are Reduced by Anti-Retroviral Therapy

    PubMed Central

    Anraku, Itaru; Rajasuriar, Reena; Dobbin, Caroline; Brown, Richard; Lewin, Sharon R.; Suhrbier, Andreas

    2012-01-01

    Circulating heat shock protein 60 (Hsp60) and heat shock protein 10 (Hsp10) have been associated with pro- and anti-inflammatory activity, respectively. To determine whether these heat shock proteins might be associated with the immune activation seen in HIV-infected patients, the plasma levels of Hsp60 and Hsp10 were determined in a cohort of 20 HIV-infected patients before and after effective combination anti-retroviral therapy (cART). We show for the first time that circulating Hsp60 levels are elevated in HIV-infected patients, with levels significantly reduced after cART, but still higher than those in HIV-negative individuals. Hsp60 levels correlated significantly with viral load, CD4 counts, and circulating soluble CD14 and lipopolysaccharide levels. No differences or correlations were seen for Hsp10 levels. Elevated circulating Hsp60 may contribute to the immune dysfunction and non-AIDS clinical events seen in HIV-infected patients. PMID:23028910

  20. Overexpression of hydroxynitrile lyase in cassava roots elevates protein and free amino acids while reducing residual cyanogen levels.

    PubMed

    Narayanan, Narayanan N; Ihemere, Uzoma; Ellery, Claire; Sayre, Richard T

    2011-01-01

    Cassava is the major source of calories for more than 250 million Sub-Saharan Africans, however, it has the lowest protein-to-energy ratio of any major staple food crop in the world. A cassava-based diet provides less than 30% of the minimum daily requirement for protein. Moreover, both leaves and roots contain potentially toxic levels of cyanogenic glucosides. The major cyanogen in cassava is linamarin which is stored in the vacuole. Upon tissue disruption linamarin is deglycosylated by the apolplastic enzyme, linamarase, producing acetone cyanohydrin. Acetone cyanohydrin can spontaneously decompose at pHs >5.0 or temperatures >35°C, or is enzymatically broken down by hydroxynitrile lyase (HNL) to produce acetone and free cyanide which is then volatilized. Unlike leaves, cassava roots have little HNL activity. The lack of HNL activity in roots is associated with the accumulation of potentially toxic levels of acetone cyanohydrin in poorly processed roots. We hypothesized that the over-expression of HNL in cassava roots under the control of a root-specific, patatin promoter would not only accelerate cyanogenesis during food processing, resulting in a safer food product, but lead to increased root protein levels since HNL is sequestered in the cell wall. Transgenic lines expressing a patatin-driven HNL gene construct exhibited a 2-20 fold increase in relative HNL mRNA levels in roots when compared with wild type resulting in a threefold increase in total root protein in 7 month old plants. After food processing, HNL overexpressing lines had substantially reduced acetone cyanohydrin and cyanide levels in roots relative to wild-type roots. Furthermore, steady state linamarin levels in intact tissues were reduced by 80% in transgenic cassava roots. These results suggest that enhanced linamarin metabolism contributed to the elevated root protein levels. PMID:21799761

  1. A retrospective examination of in-home educational visits to reduce childhood lead levels

    SciTech Connect

    Schultz, B. |; Pawel, D.; Murphy, A.

    1999-05-01

    A number of human health effects from lead are well known. However, the means for reducing lead exposure in children has been a subject of uncertainty. This paper presents results of a retrospective study of educational lead reduction interventions in Milwaukee, Wisconsin for children who had elevated blood lead levels between 20 and 24 {micro}g/dl. The study examined Milwaukee Health Department (MHD) records of baseline and follow-up blood lead measurements. A study group of children received an in-home educational visit by an MHD paraprofessional. The educational visits last about an hour and the importance of reducing lead exposure, nutritional suggestions, and dust clean-up practices and behavioral changes that can reduce lead exposure are discussed. After the intervention, the average observed blood lead level declined by 4.2 {micro}g/dl or by about 21%. A decline of 1.2 {micro}g/dl (6%) was also observed in a reference group of 226 children who did not receive an MHD in-home visit. The decline in the reference group may be partially due to education at the clinics taking the blood samples. The study group had a decline in blood lead levels 3.1 {micro}g/dl (15%) greater than the reference group, with the difference between groups being statistically significant with a P value of less than 0.001. Although significant exposures remained in most of the children studied, important lead reductions were observed with this relatively inexpensive and simple intervention. Education in the homes of families at risk for lead poisoning may be an effective component of programs to reduce blood lead levels.

  2. Reducing Benzene and Cresol Levels in National Renewable Energy Laboratory's Pilot-Scale Biorefinergy Scrubber Water

    SciTech Connect

    Buzek, M.L.; Phillips, S.

    2004-01-01

    The Thermochemical Process Development Unit at the National Renewable Energy Laboratory converts biomass into energy by gasification or pyrolysis. The aqueous effluent generated in these processes must be disposed of as hazardous waste according to the Resource Conservation and Recovery Act because certain components exceed the regulatory concentration limit. Gas stripping of the scrubber water was investigated as a method of reducing benzene and cresol levels. A custom-designed packed-bed column was built and a half-factorial experimental design was implemented to determine the effects of gas flow rate, liquid flow rate, and column packing height on the final benzene concentration in the liquid. The experimental results show that packing height had a significant effect on final benzene concentration; gas flow rate and liquid flow rate had little effect. The effects of each design variable on final cresol concentration were not determined. Although the current column design did significantly reduce the benzene and cresol levels in the scrubber water, it did not reduce the concentrations below the regulatory limits. A full-factorial experimental design will be implemented with an increased packing height. Other variables, including column diameter and packing type, will be investigated to determine their effects on final benzene and cresol concentrations. Once the packed-bed column is determined to be effective in reducing contaminant concentrations below the regulatory limit, photocatalytic oxidation will be explored for remediating the benzene and cresol from the gas stream.

  3. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions

    PubMed Central

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E.

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  4. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions.

    PubMed

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  5. 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

  6. Passive stretch reduces calpain activity through nitric oxide pathway in unloaded soleus muscles.

    PubMed

    Xu, Peng-Tao; Li, Quan; Sheng, Juan-Juan; Chang, Hui; Song, Zhen; Yu, Zhi-Bin

    2012-08-01

    Unloading in spaceflight or long-term bed rest induces to pronounced atrophy of anti-gravity skeletal muscles. Passive stretch partially resists unloading-induced atrophy of skeletal muscle, but the mechanism remains elusive. The aims of this study were to investigate the hypotheses that stretch tension might increase protein level of neuronal nitric oxide synthase (nNOS) in unloaded skeletal muscle, and then nNOS-derived NO alleviated atrophy of skeletal muscle by inhibiting calpain activity. The tail-suspended rats were used to unload rat hindlimbs for 2 weeks, at the same time, left soleus muscle was stretched by applying a plaster cast to fix the ankle at 35° dorsiflexion. Stretch partially resisted atrophy and inhibited the decreased protein level and activity of nNOS in unloaded soleus muscles. Unloading increased frequency of calcium sparks and elevated intracellular resting and caffeine-induced Ca(2+) concentration ([Ca(2+)]i) in unloaded soleus muscle fibers. Stretch reduced frequency of calcium sparks and restored intracellular resting and caffeine-induced Ca(2+) concentration to control levels in unloaded soleus muscle fibers. The increased protein level and activity of calpain as well as the higher degradation of desmin induced by unloading were inhibited by stretch in soleus muscles. In conclusion, these results suggest that stretch can preserve the stability of sarcoplasmic reticulum Ca(2+) release channels which prevents the elevated [Ca(2+)]i by means of keeping nNOS activity, and then the enhanced protein level and activity of calpain return to control levels in unloaded soleus muscles. Therefore, stretch can resist in part atrophy of unloaded soleus muscles. PMID:22547201

  7. QMix® irrigant reduces lipopolysacharide (LPS) levels in an in vitro model

    PubMed Central

    GRÜNDLING, Grasiela Longhi; de MELO, Tiago André Fontoura; MONTAGNER, Francisco; SCARPARO, Roberta Kochenborger; VIER-PELISSER, Fabiana Vieira

    2015-01-01

    The presence of endotoxin inside the root canal has been associated with periapical inflammation, bone resorption and symptomatic conditions. Objectives To determine, in vitro, the effect of QMix® and other three root canal irrigants in reducing the endotoxin content in root canals. Material and Methods Root canals of single-rooted teeth were prepared. Samples were detoxified with Co-60 irradiation and inoculated with E. coli LPS (24 h, at 37°C). After that period, samples were divided into 4 groups, according to the irrigation solution tested: QMix®, 17% EDTA, 2% chlorhexidine solution (CHX), and 3% sodium hypochlorite (NaOCl). LPS quantification was determined by Limulus Amebocyte Lysate (LAL) assay. The initial counting of endotoxins for all samples, and the determination of LPS levels in non-contaminated teeth and in contaminated teeth exposed only to non-pyrogenic water, were used as controls. Results QMix® reduced LPS levels, with a median value of 1.11 endotoxins units (EU)/mL (p<0.001). NaOCl (25.50 EU/mL), chlorhexidine (44.10 EU/mL) and positive control group (26.80 EU/mL) samples had similar results. Higher levels were found with EDTA (176.00 EU/mL) when compared to positive control (p<0.001). There was no significant difference among EDTA, NaOCl and CHX groups. Negative control group (0.005 EU/mL) had statistically significant lower levels of endotoxins when compared to all test groups (p<0.001). Conclusion QMix® decreased LPS levels when compared to the other groups (p<0.001). 3% NaOCl, 2% CHX and 17% EDTA were not able to significantly reduce the root canal endotoxins load. PMID:26398517

  8. QMix® irrigant reduces lipopolysacharide (LPS) levels in an in vitro model.

    PubMed

    Gründling, Grasiela Longhi; Melo, Tiago André Fontoura de; Montagner, Francisco; Scarparo, Roberta Kochenborger; Vier-Pelisser, Fabiana Vieira

    2015-01-01

    The presence of endotoxin inside the root canal has been associated with periapical inflammation, bone resorption and symptomatic conditions.Objectives To determine, in vitro, the effect of QMix® and other three root canal irrigants in reducing the endotoxin content in root canals.Material and Methods Root canals of single-rooted teeth were prepared. Samples were detoxified with Co-60 irradiation and inoculated with E. coli LPS (24 h, at 37°C). After that period, samples were divided into 4 groups, according to the irrigation solution tested: QMix®, 17% EDTA, 2% chlorhexidine solution (CHX), and 3% sodium hypochlorite (NaOCl). LPS quantification was determined by Limulus Amebocyte Lysate (LAL) assay. The initial counting of endotoxins for all samples, and the determination of LPS levels in non-contaminated teeth and in contaminated teeth exposed only to non-pyrogenic water, were used as controls.Results QMix® reduced LPS levels, with a median value of 1.11 endotoxins units (EU)/mL (p<0.001). NaOCl (25.50 EU/mL), chlorhexidine (44.10 EU/mL) and positive control group (26.80 EU/mL) samples had similar results. Higher levels were found with EDTA (176.00 EU/mL) when compared to positive control (p<0.001). There was no significant difference among EDTA, NaOCl and CHX groups. Negative control group (0.005 EU/mL) had statistically significant lower levels of endotoxins when compared to all test groups (p<0.001).Conclusion QMix® decreased LPS levels when compared to the other groups (p<0.001). 3% NaOCl, 2% CHX and 17% EDTA were not able to significantly reduce the root canal endotoxins load. PMID:26398517

  9. High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.

    PubMed

    Mangialasche, Francesca; Kivipelto, Miia; Mecocci, Patrizia; Rizzuto, Debora; Palmer, Katie; Winblad, Bengt; Fratiglioni, Laura

    2010-01-01

    In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated. PMID:20413888

  10. Disruption of Adenosine-5′-Phosphosulfate Kinase in Arabidopsis Reduces Levels of Sulfated Secondary Metabolites[W

    PubMed Central

    Mugford, Sarah G.; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T.; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-01-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5′-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3′-phosphoadenosine 5′-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  11. 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…

  12. APATHY AND APOE4 ARE ASSOCIATED WITH REDUCED BDNF LEVELS IN ALZHEIMER’S DISEASE

    PubMed Central

    Álvarez, Antón; Aleixandre, Manuel; Linares, Carlos; Masliah, Eliezer; Moessler, Herbert

    2016-01-01

    Reduced brain-derived neurotrophic factor (BDNF) signaling is considered as a pathogenic event in early Alzheimer’s disease (AD), but the influence of apathy and apolipoprotein E epsilon-4 allele (APOE4) on serum BDNF values was not previously investigated in AD. We evaluated serum BDNF levels in AD, amnestic mild cognitive impairment (MCI) and control subjects. Baseline BDNF levels were similar in AD, MCI and controls. AD patients having apathy showed lower BDNF values than patients without apathy (p<0.05). After correction for the influence of apathy, APOE4 carriers showed lower BDNF levels (p<0.01) and MMSE scores (p<0.01) than non-APOE4 carriers in the subgroup of AD females, but not in males. Significant (p<0.05) positive correlations between BDNF values and MMSE scores were only observed in subgroups of AD males and of AD patients without apathy. These results are showing the association of apathy and APOE4 with reduced serum BDNF levels in AD, and are suggesting that BDNF reductions might contribute to the worse cognitive performance exhibited by AD apathetic patients and female APOE4 carriers. PMID:25024337

  13. Preventing and reducing violence against women: innovation in community-level studies.

    PubMed

    Taft, Angela; Small, Rhonda

    2014-01-01

    Intimate partner violence is a serious global problem that damages the health and prosperity of individuals, their families, community, and society. WHO endorses an 'ecological model,' which states that there are multi-level intersecting factors enabling perpetration and victimization of violence. Intervention science to prevent or reduce the problem is in its infancy, and the few existing intervention studies have been targeted at the individual level. In a recent study published in BMC Medicine, Abramsky et al. bring innovation to the field, targeting their intervention trial "SASA!" in Kampala Uganda at all ecological levels, but particularly at the community level. Recruiting and training both male and female community leaders and activists who enabled group and media discussions, the authors focused on the beneficial and abusive detrimental uses of power rather than commencing with the central issue of gender inequality. SASA! successfully reduced community attitudes to tolerance of violence and inequality, men's sexual risk behaviors, and women's experience of physical violence. The study also improved the communities' response to victimized women. SASA! has promise for adaptation and replication in low, middle and high income countries. Please see related article: http://www.biomedcentral.com/1741-7015/12/122. PMID:25286152

  14. Nutrient Plasma Levels Achieved During Treatment that Reduces Noise-Induced Hearing Loss

    PubMed Central

    Le Prell, C. G.; Dolan, D. F.; Bennett, D. C.; Boxer, P. A.

    2011-01-01

    Hearing loss encompasses both temporary and permanent deficits. If temporary threshold shift (TTS) and permanent threshold shift (PTS) share common pathological mechanisms, then agents that reduce PTS should also reduce TTS. Several antioxidant agents have reduced PTS in rodent models; however, reductions in TTS have been inconsistent. This study first determined whether dietary antioxidants (beta-carotene, and vitamins C and E) delivered in combination with magnesium (Mg) reliably increase plasma concentrations of the active agents. Then, additional manipulations tested the hypothesis that these nutrients reduce acute TTS insult in the first 24 hours following loud sound, as well as longer lasting changes in hearing measured up to 7 days post-noise. Saline or nutrients were administered to guinea pigs prior to and after noise exposure. Sound-evoked electrophysiological responses were measured before noise, with tests repeated 1-hour post-noise, as well as 1-, 3-, 5-, and 7-days post-noise. All subjects showed significant functional recovery; subjects treated with nutrients recovered more rapidly, and had better hearing outcomes at early post-noise times as well as the final test time. Thus, this combination of nutrients, which produced significant increases in plasma concentrations of vitamins C and E and Mg, effectively reduced hearing loss at multiple post-noise times. These data suggest free radical formation contributes to TTS as well as PTS insults, and suggest a potential opportunity to prevent TTS in human populations. PMID:21708356

  15. 34 CFR 300.704 - State-level activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false State-level activities. 300.704 Section 300.704... Allotments, Grants, and Use of Funds § 300.704 State-level activities. (a) State administration. (1) For the... may be used for the administration of Part C of the Act, if the SEA is the lead agency for the...

  16. 34 CFR 300.704 - State-level activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true State-level activities. 300.704 Section 300.704... Allotments, Grants, and Use of Funds § 300.704 State-level activities. (a) State administration. (1) For the... may be used for the administration of Part C of the Act, if the SEA is the lead agency for the...

  17. Middle Level Activities To Involve the Invisible Student.

    ERIC Educational Resources Information Center

    Rimmer, Sue; Arico, Jim

    Involvement in student activities has many advantages for the middle level student. Such activities promote achievement, citizenship, and service to the community while developing self-esteem, self-confidence, and social cooperation. This book is intended as a tool for middle level schools to motivate, develop, guide, involve, and provide middle…

  18. Physical Activity Levels during Adventure-Physical Education Lessons

    ERIC Educational Resources Information Center

    Gehris, Jeffrey; Myers, Elizabeth; Whitaker, Robert

    2012-01-01

    Adventure-physical education has been proposed to promote adolescents' physical development, but little is known about physical activity levels during such lessons. Using the System for Observing Fitness Instruction Time, we observed students' (ages 11-14 years) physical activity levels in co-educational classes during 43 adventure-physical…

  19. Reduced peroxisomal citrate synthase activity increases substrate availability for polyhydroxyalkanoate biosynthesis in plant peroxisomes.

    PubMed

    Tilbrook, Kimberley; Poirier, Yves; Gebbie, Leigh; Schenk, Peer M; McQualter, Richard B; Brumbley, Stevens M

    2014-10-01

    Polyhydroxyalkanoates (PHAs) are bacterial carbon storage polymers used as renewable, biodegradable plastics. PHA production in plants may be a way to reduce industrial PHA production costs. We recently demonstrated a promising level of peroxisomal PHA production in the high biomass crop species sugarcane. However, further production strategies are needed to boost PHA accumulation closer to commercial targets. Through exogenous fatty acid feeding of Arabidopsis thaliana plants that contain peroxisome-targeted PhaA, PhaB and PhaC enzymes from Cupriavidus necator, we show here that the availability of substrates derived from the β-oxidation cycle limits peroxisomal polyhydroxybutyrate (PHB) biosynthesis. Knockdown of peroxisomal citrate synthase activity using artificial microRNA increased PHB production levels approximately threefold. This work demonstrates that reduction of peroxisomal citrate synthase activity may be a valid metabolic engineering strategy for increasing PHA production in other plant species. PMID:24944109

  20. Helicopter far-field acoustic levels as a function of reduced rotor speeds

    NASA Technical Reports Server (NTRS)

    Mueller, Arnold W.; Lemasurier, Philip; Smith, Charles D.

    1990-01-01

    This paper will present far-field measured noise levels relative to tests conducted with a model S-76A helicopter. The project was designed to provide supplemental experimental flight data which may be used to further study reduced helicopter rotor speeds (and thus, advancing blade-tip Mach number) effects on far-field acoustic levels. The aircraft was flown in straight and level flight while operating with both the rotor speed and flight speed as test variables. The rotor speed was varied over the range of 107 percent of the main-rotor speed (NR) to 90 percent NR and with the forward flight speed varied over the range of 155 to 35 knots indicated air speed. These conditions produced a wide range of advancing blade-tip Mach numbers to which the noise data are related.

  1. Flea fitness is reduced by high fractional concentrations of CO₂ that simulate levels found in their hosts' burrows.

    PubMed

    Downs, Cynthia J; Pinshow, Berry; Khokhlova, Irina S; Krasnov, Boris R

    2015-11-01

    Nidicolous ectoparasites such as fleas and gamasid mites that feed on small and medium-sized mammals spend much of their time in their hosts' burrows, which provide an environment for living, and often feeding, to their pre-imaginal and/or adult stages. Thus, these ectoparasites should be adapted to environmental conditions in burrows, including high fractional concentrations of CO2 (F(CO2)). We examined how a high F(CO2) (0.04) affected survival and reproductive success of a hematophagous ectoparasite of burrowing rodents using fleas Xenopsylla ramesis and Sundevall's jirds Meriones crassus. In the first experiment, fleas fed on hosts housed in high-CO2 (F(CO2) =0.04) or atmospheric-CO2 (F(CO2) ≈0.0004) air, and were allowed to breed. In a second experiment, fleas were maintained in high CO2 or CO2-free air with no hosts to determine how CO2 levels affect survival and activity levels. We found that at high F(CO2) fleas laid fewer eggs, reducing reproductive success. In addition, at high F(CO2), activity levels and survival of fleas were reduced. Our results indicate that fleas do not perform well in the F(CO2) used in this experiment. Previous research indicated that the type and intensity of the effects of CO2 concentration on the fitness of an insect depend on the F(CO2) used, so we advise caution when generalizing inferences drawn to insects exposed to other F(CO2). If, however, F(CO2) found in natural mammal burrows brings about reduced fitness in fleas in general, then burrowing hosts may benefit from reduced parasite infestation if burrow air F(CO2) is high. PMID:26582933

  2. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth

    PubMed Central

    Rogan, Mark P.; Reznikov, Leah R.; Pezzulo, Alejandro A.; Gansemer, Nicholas D.; Samuel, Melissa; Prather, Randall S.; Zabner, Joseph; Fredericks, Douglas C.; McCray, Paul B.; Welsh, Michael J.; Stoltz, David A.

    2010-01-01

    People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF. PMID:21059918

  3. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth.

    PubMed

    Rogan, Mark P; Reznikov, Leah R; Pezzulo, Alejandro A; Gansemer, Nicholas D; Samuel, Melissa; Prather, Randall S; Zabner, Joseph; Fredericks, Douglas C; McCray, Paul B; Welsh, Michael J; Stoltz, David A

    2010-11-23

    People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF. PMID:21059918

  4. Adipose Mesenchymal Stromal Cells Isolated From Type 2 Diabetic Patients Display Reduced Fibrinolytic Activity

    PubMed Central

    Acosta, Lourdes; Hmadcha, Abdelkrim; Escacena, Natalia; Pérez-Camacho, Inmaculada; de la Cuesta, Antonio; Ruiz-Salmeron, Rafael; Gauthier, Benoit R.; Soria, Bernat

    2013-01-01

    Stem cells have been successfully used for the treatment of critical limb ischemia (CLI). We conducted a clinical trial to determine the feasibility of using autologous adipose-derived mesenchymal stromal cells (AdMSCs) for the treatment of CLI. Unexpectedly, two diabetic patients developed peripheral microthrombosis. This adverse effect, which contrasts with the reported antithrombotic properties of MSCs, may stem from the diabetic environment that alters the fibrinolytic activity of AdMSCs, thereby increasing the probability of developing thrombosis. Here, we confirm this premise by demonstrating that diabetic AdMSCs cultured in the presence of blood sera expressed and released higher levels of plasminogen activator inhibitor type 1, reduced levels of tissue plasminogen activator, and lower d-dimer formation compared with nondiabetic AdMSCs. Thus, to establish an appropriate cell therapy for diabetic patients, we recommend including new preclinical safety tests, such as the d-dimer and/or the tissue plasminogen activator-to-plasminogen activator inhibitor type 1 ratio tests, to assess fibrinolytic activity of cells before implantation. PMID:24043757

  5. Oral midazolam reduces cortisol levels during local anaesthesia in children: a randomised controlled trial.

    PubMed

    Gomes, Heloisa Sousa; Corrêa-Faria, Patrícia; Silva, Tarcília Aparecida; Paiva, Saul Martins; Costa, Paulo Sérgio Sucasas; Batista, Aline Carvalho; Costa, Luciane Rezende

    2015-01-01

    Little is known about whether midazolam sedation can reduce salivary cortisol levels and consequently influence children's behaviour during dental treatment. The aim of this study was to evaluate the effect of midazolam sedation on salivary cortisol and its correlation with children's behaviour during restorative dental treatment. Eighteen healthy children, aged two to five years, were randomly assigned to two dental treatment appointments, both with physical restraint: oral midazolam 1 mg/kg (MS) and placebo (PS). An observer assessed the children's behaviour (videos) using the Ohio State University Behavioral Rating Scale (OSUBRS). The children's saliva was collected just after waking up, on arrival at the dental school, 25 minutes after local anaesthesia, and 25 minutes after the end of the procedure. Salivary cortisol levels were determined using the enzyme-linked immunoabsorbent assay. The data were analysed by bivariate tests and multivariate analysis of variance (5% level). Salivary cortisol levels were lower in the MS group than in the PS group at the time of anaesthesia (p = 0.004), but did not vary during the appointment within sedation (p = 0.319) or placebo (p = 0.080) groups. Children's behaviour was negative most of the time and did not differ between MS and PS; however, the behaviour (OSUBRS) did not correlate with salivary cortisol levels. Oral midazolam is able to control salivary cortisol levels during dental treatment of pre-schoolers, which might not lead to better clinical behaviour. PMID:26892359

  6. Millimeter-Wave Measurements of High Level and Low Level Activity Glass Melts

    SciTech Connect

    Woskov, Paul P.; Sundaram, S.K.; Daniel, William E., Jr.

    2006-06-01

    The primary objectives of the current research is to develop on-line sensors for characterizing molten glass in high-level and low-activity waste glass melters using millimeter-wave (MMW) technology and to use this technology to do novel research of melt dynamics. Existing and planned waste glass melters lack sophisticated diagnostics due to the hot, corrosive, and radioactive melter environments. Without process control diagnostics, the Defense Waste Processing Facility (DWPF) and the Waste Treatment Plant (WTP) under construction at Hanford operate by a feed forward process control scheme that relies on predictive models with large uncertainties. This scheme severely limits production throughput and waste loading. Also operations at DWPF have shown susceptibility to anomalies such as pouring, foaming, and combustion gas build up, which can seriously disrupt operations. Future waste chemistries will be even more challenging. The scientific goals of this project are to develop new reliable on-line monitoring capability for important glass process parameters such as temperature profiles, emissivity, density, viscosity, and other characteristics using the unique advantages of millimeter wave electromagnetic radiation that can be eventually implemented in the operating melters. Once successfully developed and implemented, significant cost savings would be realized in melter operations by increasing production through put, reduced storage volumes (through higher waste loading), and reduced risks (prevention or mitigation of anomalies).

  7. Maintain levels of nicotine but reduce other smoke constituents: a formula for ''less-hazardous'' cigarettes

    SciTech Connect

    Robinson, J.C.; Young, J.C.; Rickert, W.S.

    1984-09-01

    Twenty-two volunteers who smoked more than 20 cigarettes with ''high'' nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. During the final 5 weeks (P2), the treatment group (16 subjects) switched to the ''light'' version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of ''less-hazardous'' cigarettes.

  8. High serum levels of proinflammatory markers during epileptogenesis. Can omega-3 fatty acid administration reduce this process?

    PubMed

    Gouveia, Telma Luciana Furtado; Vieira de Sousa, Paula Viviane; de Almeida, Sandro Soares; Nejm, Mariana Bocca; Vieira de Brito, Joíse Marques; Cysneiros, Roberta Monterazzo; de Brito, Marlon Vilela; Salu, Bruno Ramos; Oliva, Maria Luiza Vilela; Scorza, Fúlvio Alexandre; Naffah-Mazzacoratti, Maria da Graça

    2015-10-01

    During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures. PMID:26318793

  9. Increased Hepatic Fatty Acids Uptake and Oxidation by LRPPRC-Driven Oxidative Phosphorylation Reduces Blood Lipid Levels

    PubMed Central

    Lei, Shi; Sun, Run-zhu; Wang, Di; Gong, Mei-zhen; Su, Xiang-ping; Yi, Fei; Peng, Zheng-wu

    2016-01-01

    Hyperlipidemia is one of the major risk factors of atherosclerosis and other cardiovascular diseases. This study aimed to investigate the impact of leucine rich pentatricopeptide repeat containing protein (LRPPRC)-driven hepatic oxidative phoshorylation on blood lipid levels. The hepatic LRPPRC level was modulated by liver-specific transgenic or adeno-associated virus 8 carried shRNA targeting Lrpprc (aav-shLrpprc). Mice were fed with a high fat diet to induce obesity. Gene expression was analyzed by quantitative real-time PCR and / or western blot. The hepatic ATP level, hepatic and serum lipids contents, and mitochondria oxidative phosphorylation (OxPhos) complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using 14C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, OxPhos, and lipid metabolism. Increased OxPhos in liver mediated by LRPPRC resulted in the increase of hepatic ATP level. Lrpprc promoted palmitate uptake and oxidation by hypatocytes. The hepatic and serum triglyceride and total cholesterol levels were inversely associated with the hepatic LRPPRC level. These data demonstrated that LRPPRC-driven hepatic OxPhos could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels. PMID:27462273

  10. Increased Hepatic Fatty Acids Uptake and Oxidation by LRPPRC-Driven Oxidative Phosphorylation Reduces Blood Lipid Levels.

    PubMed

    Lei, Shi; Sun, Run-Zhu; Wang, Di; Gong, Mei-Zhen; Su, Xiang-Ping; Yi, Fei; Peng, Zheng-Wu

    2016-01-01

    Hyperlipidemia is one of the major risk factors of atherosclerosis and other cardiovascular diseases. This study aimed to investigate the impact of leucine rich pentatricopeptide repeat containing protein (LRPPRC)-driven hepatic oxidative phoshorylation on blood lipid levels. The hepatic LRPPRC level was modulated by liver-specific transgenic or adeno-associated virus 8 carried shRNA targeting Lrpprc (aav-shLrpprc). Mice were fed with a high fat diet to induce obesity. Gene expression was analyzed by quantitative real-time PCR and / or western blot. The hepatic ATP level, hepatic and serum lipids contents, and mitochondria oxidative phosphorylation (OxPhos) complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using (14)C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, OxPhos, and lipid metabolism. Increased OxPhos in liver mediated by LRPPRC resulted in the increase of hepatic ATP level. Lrpprc promoted palmitate uptake and oxidation by hypatocytes. The hepatic and serum triglyceride and total cholesterol levels were inversely associated with the hepatic LRPPRC level. These data demonstrated that LRPPRC-driven hepatic OxPhos could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels. PMID:27462273

  11. Activity Levels in Healthy Older Adults: Implications for Joint Arthroplasty

    PubMed Central

    Thorp, Laura E.; Orozco, Diego; Block, Joel A.; Sumner, Dale R.; Wimmer, Markus A.

    2012-01-01

    This work evaluated activity levels in a group of healthy older adults to establish a target activity level for adults of similar age after total joint arthroplasty (TJA). With the decreasing age of TJA patients, it is essential to have a reference for activity level in younger patients as activity level affects quality of life and implant design. 54 asymptomatic, healthy older adults with no clinical evidence of lower extremity OA participated. The main outcome measure, average daily step count, was measured using an accelerometer-based activity monitor. On average the group took 8813 ± 3611 steps per day, approximately 4000 more steps per day than has been previously reported in patients following total joint arthroplasty. The present work provides a reference for activity after joint arthroplasty which is relevant given the projected number of people under the age of 65 who will undergo joint arthroplasty in the coming years. PMID:23577274

  12. Leptin resistance is not the primary cause of weight gain associated with reduced sex hormone levels in female mice.

    PubMed

    da Silva, Regina P; Zampieri, Thais T; Pedroso, João A B; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; Furigo, Isadora C; Câmara, Niels O; Frazão, Renata; Donato, Jose

    2014-11-01

    Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state. PMID:25144922

  13. Self-Rated Activity Levels and Longevity: Evidence from a 20 Year Longitudinal Study

    ERIC Educational Resources Information Center

    Mullee, Mark A.; Coleman, Peter G.; Briggs, Roger S. J.; Stevenson, James E.; Turnbull, Joanne C.

    2008-01-01

    The study reports on factors predicting the longevity of 328 people over the age of 65 drawn from an English city and followed over 20 years. Both the reported activities score and the individual's comparative evaluation of their own level of activity independently reduced the risk of death, even when health and cognitive status were taken into…

  14. 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

  15. Towards a new paradigm: Activity level balanced sustainability reporting.

    PubMed

    Samudhram, Ananda; Siew, Eu-Gene; Sinnakkannu, Jothee; Yeow, Paul H P

    2016-11-01

    Technoeconomic paradigms based economic growth theories suggest that waves of technological innovations drove the economic growth of advanced economies. Widespread economic degradation and pollution is an unintended consequence of such growth. Tackling environmental and social issues at firm levels would help us to overcome such issues at macro-levels. Consequently, the Triple Bottom Line (TBL) reporting approach promotes firm level economic, environmental and social performances. Incorporating Zink's (2014) 3-pillar presentation model, this paper indicates that economic, social and environmental performances tend to be reported at firm level. All three pillars are not covered evenly at the activity levels. Thus, a loophole is identified whereby excellent environmental performance at activity levels could potentially leave poor social performance undisclosed. A refinement of the TBL paradigm, whereby all three pillars are covered at the activity level, is suggested, to enhance sustainability reporting. PMID:27029522

  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. Analysis of intracellular reducing levels in human hepatocytes on three-dimensional focusing microchip.

    PubMed

    Xu, Chunxiu; Cai, Longfei

    2014-02-01

    A novel three-dimensional hydrodynamic focusing microfluidic device integrated with high-throughput cell sampling and detection of intracellular contents is presented. It has a pivotal role in maintaining the reducing environment in cells. Intracellular reducing species such as vitamin C and glutathione in normal and tumor cells were labeled by a newly synthesized 2,2,6,6-tetramethyl-piperidine-1-oxyl-based fluorescent probe. Hepatocytes are adherent cells, which are prone to attaching to the channel surface. To avoid the attachment of cells on the channel surface, a single channel microchip with three sheath-flow channels located on both sides of and below the sampling channel was developed. Hydrostatic pressure generated by emptying the sample waste reservoir was used as driving force of fluid on the microchip. Owing to the difference between the liquid levels of the reservoirs, the labeled cells were three-dimensional hydrodynamically focused and transported from the sample reservoir to the sample waste reservoir. Hydrostatic pressure takes advantage of its ease of generation on a microfluidic chip without any external pressure pump, which drives three sheath-flow streams to constrain a sample flow stream into a narrow stream to avoid blockage of the sampling channel by adhered cells. The intracellular reducing levels of HepG2 cells and L02 cells were detected by home-built laser-induced fluorescence detector. The analysis throughput achieved in this microfluidic system was about 59-68 cells/min. PMID:23297173

  18. Solar Activity, Different Geomagnetic Activity Levels and Acute Myocardial Infarction

    NASA Astrophysics Data System (ADS)

    Dimitrova, Svetla; Jordanova, Malina; Stoilova, Irina; Taseva, Tatiana; Maslarov, Dimitar

    Results on revealing a possible relationship between solar activity (SA) and geomagnetic activity (GMA) and acute myocardial infarction (AMI) morbidity are presented. Studies were based on medical data covering the period from 1.12.1995 to 31.12.2004 and concerned daily distribution of patients with AMI diagnose (in total 1192 cases) from Sofia region on the day of admission at the hospital. Analysis of variance (ANOVA) was applied to check the significance of GMA intensity effect and the type of geomagnetic storms, those caused by Magnetic Clouds (MC) and by High Speed Solar Wind Streams (HSSWS), on AMI morbidity. Relevant correlation coefficients were calculated. Results revealed statistically significant positive correlation between considered GMA indices and AMI. ANOVA revealed that AMI number was signifi- cantly increased from the day before (-1st) till the day after (+1st) geomagnetic storms with different intensities. Geomagnetic storms caused by MC were related to significant increase of AMI number in comparison with the storms caused by HSSWS. There was a trend for such different effects even on -1st and +1st day.

  19. 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.

  20. Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

    PubMed Central

    Munari, Enrico; Chaux, Alcides; Vaghasia, Ajay M.; Taheri, Diana; Karram, Sarah; Bezerra, Stephania M.; Gonzalez Roibon, Nilda; Nelson, William G.; Yegnasubramanian, Srinivasan; Netto, George J.; Haffner, Michael C.

    2016-01-01

    Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. PMID:26785262

  1. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    PubMed

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  2. Obesity reduces methionine sulfoxide reductase activity in visceral adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Visceral obesity is linked to the development of comorbidities including insulin resistance and cardiovascular disease. Elevated levels of oxidative stress are observed in obese individuals and in animal models of obesity, pointing to a mechanistic role of oxidative stress. A recent genetic study in...

  3. Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

    SciTech Connect

    Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

    1987-03-01

    Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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…

  9. Experimentally elevated levels of testosterone at independence reduce fitness in a territorial bird.

    PubMed

    Martínez-Padilla, J; Pérez-Rodríguez, L; Mougeot, F; Ludwig, S C; Redpath, S M

    2014-04-01

    Environmental conditions and individual strategies in early life may have a profound effect on fitness. A critical moment in the life of an organism occurs when an individual reaches independence and stops receiving benefits from its relatives. Understanding the consequences of individual strategies at the time of independence requires quantification of their fitness effects. We explored this period in the Red Grouse (Lagopus lagopus scoticus). In this system, testosterone and parasite (Trichostrongylus tenuis) levels are known to influence survival and reproduction, the two key components of individual fitness. We experimentally and simultaneously manipulated testosterone and parasites at three levels (high, intermediate, and control levels for both factors) in 195 young males in five populations using a factorial experimental design. We explored the effects of our treatments on fitness by monitoring reproduction and survival throughout the life of all males and estimating lambda(ind), a rate-sensitive index of fitness. Parasite challenges increased the number of worms with a time lag, as previously found. However, we did not find significant effects of parasite manipulations on fitness, possibly because parasite abundance did not increase to harmful levels. Our hormone manipulation was successful at increasing testosterone at three different levels. Such increases in hormone levels decreased overall fitness. This was caused by reduced offspring production in the first breeding attempt rather than by any effect of the treatment on bird survival. Our results highlight that investing in high testosterone levels at independence, a strategy that might enhance short-term recruitment probability in territorial species such as Red Grouse, has a fitness cost, and can influence the resolution of the trade-off between reproduction and survival later in life. PMID:24933821

  10. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  11. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

    PubMed Central

    Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

    2015-01-01

    Designing culturally-sensitive personalized interventions is essential to sustain patients’ involvement in their treatment, and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and self-determination for their own health and health care. We propose a patient-centered, multi-level activation and empowerment framework (individual-, health care professional-, community-, and health care delivery system-level) to inform the development of culturally informed personalized patient activation and empowerment (P-PAE) interventions to improve population health, and reduce racial and ethnic disparities. We discuss relevant Affordable Care Act payment and delivery policy reforms, and how they impact patient activation and empowerment. Such policies include Accountable Care Organizations and Value Based Purchasing, Patient Centered Medical Homes, and the Community Health Benefit. Challenges and possible solutions to implementing the P-PAE are discussed. Comprehensive and longitudinal data sets with consistent P-PAE measures are needed to conduct comparative effectiveness analyses to evaluate the optimal P-PAE model. We believe the P-PAE model is timely and sustainable, and will be critical to engaging patients in their treatment, developing patients’ abilities to manage their health, helping patients to express concerns and preferences regarding treatment, empowering patients to ask questions about treatment options, and building up strategic patient-provider partnerships through shared decision making. PMID:25845376

  12. Ferromagnetic interaction model of activity level in workplace communication

    NASA Astrophysics Data System (ADS)

    Akitomi, Tomoaki; Ara, Koji; Watanabe, Jun-ichiro; Yano, Kazuo

    2013-03-01

    The nature of human-human interaction, specifically, how people synchronize with each other in multiple-participant conversations, is described by a ferromagnetic interaction model of people’s activity levels. We found two microscopic human interaction characteristics from a real-environment face-to-face conversation. The first characteristic is that people quite regularly synchronize their activity level with that of the other participants in a conversation. The second characteristic is that the degree of synchronization increases as the number of participants increases. Based on these microscopic ferromagnetic characteristics, a “conversation activity level” was modeled according to the Ising model. The results of a simulation of activity level based on this model well reproduce macroscopic experimental measurements of activity level. This model will give a new insight into how people interact with each other in a conversation.

  13. Improving patients' sleep: reducing light and noise levels on wards at night.

    PubMed

    Hewart, Carol; Fethney, Loveday

    2016-02-01

    There is much research concerning the psychological and physical effects of sleep deprivation on patients in healthcare systems, yet interrupted sleep on hospital wards at night remains a problem. Staff at Plymouth Hospitals NHS Trust, Devon, wanted to identify the factors that prevent patients from sleeping well at night. Two audits were carried out, between April and August 2015, to assess noise and light levels on wards at night, and to engage nurses in ways of reducing these. A number of recommendations were made based on the audit findings, many of which have been put into practice. PMID:26938911

  14. Phosphorus speciation by coupled HPLC-ICPMS: low level determination of reduced phosphorus in natural materials

    NASA Astrophysics Data System (ADS)

    Atlas, Zachary; Pasek, Matthew; Sampson, Jacqueline

    2015-04-01

    Phosphorus is a geologically important minor element in the Earth's crust commonly found as relatively insoluble apatite. This constraint causes phosphorus to be a key limiting nutrient in biologic processes. Despite this, phosphorus plays a direct role in the formation of DNA, RNA and other cellular materials. Recent works suggest that since reduced phosphorus is considerably more soluble than oxidized phosphorus that it was integrally involved in the development of life on the early Earth and may continue to play a role in biologic productivity to this day. This work examines a new method for quantification and identification of reduced phosphorus as well as applications to the speciation of organo-phosphates separated by coupled HPLC - ICP-MS. We show that reduced phosphorus species (P1+, P3+ and P5+) are cleanly separated in the HPLC and coupled with the ICPMS reaction cell, using oxygen as a reaction gas to effectively convert elemental P to P-O. Analysis at M/Z= 47 producing lower background and flatter baseline chromatography than analyses performed at M/Z = 31. Results suggest very low detection limits (0.05 μM) for P species analyzed as P-O. Additionally we show that this technique has potential to speciate at least 5 other forms of phosphorus compounds. We verified the efficacy of method on numerous materials including leached Archean rocks, suburban retention pond waters, blood and urine samples and most samples show small but detectible levels of reduced phosphorus and or organo-phaospates. This finding in nearly all substances analyzed supports the assumption that the redox processing of phosphorus has played a significant role throughout the history of the Earth and it's presence in the present environment is nearly ubiquitous with the reduced oxidation state phosphorus compounds, phosphite and hypophosphite, potentially acting as significant constituents in the anaerobic environment.

  15. Reducing greenhouse gas emissions, water use, and grain arsenic levels in rice systems.

    PubMed

    Linquist, Bruce A; Anders, Merle M; Adviento-Borbe, Maria Arlene A; Chaney, Rufus L; Nalley, L Lanier; da Rosa, Eliete F F; van Kessel, Chris

    2015-01-01

    Agriculture is faced with the challenge of providing healthy food for a growing population at minimal environmental cost. Rice (Oryza sativa), the staple crop for the largest number of people on earth, is grown under flooded soil conditions and uses more water and has higher greenhouse gas (GHG) emissions than most crops. The objective of this study was to test the hypothesis that alternate wetting and drying (AWD--flooding the soil and then allowing to dry down before being reflooded) water management practices will maintain grain yields and concurrently reduce water use, greenhouse gas emissions and arsenic (As) levels in rice. Various treatments ranging in frequency and duration of AWD practices were evaluated at three locations over 2 years. Relative to the flooded control treatment and depending on the AWD treatment, yields were reduced by <1-13%; water-use efficiency was improved by 18-63%, global warming potential (GWP of CH4 and N2 O emissions) reduced by 45-90%, and grain As concentrations reduced by up to 64%. In general, as the severity of AWD increased by allowing the soil to dry out more between flood events, yields declined while the other benefits increased. The reduction in GWP was mostly attributed to a reduction in CH4 emissions as changes in N2 O emissions were minimal among treatments. When AWD was practiced early in the growing season followed by flooding for remainder of season, similar yields as the flooded control were obtained but reduced water use (18%), GWP (45%) and yield-scaled GWP (45%); although grain As concentrations were similar or higher. This highlights that multiple environmental benefits can be realized without sacrificing yield but there may be trade-offs to consider. Importantly, adoption of these practices will require that they are economically attractive and can be adapted to field scales. PMID:25099317

  16. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats

    PubMed Central

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-01-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  17. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats.

    PubMed

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-08-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  18. Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans.

    PubMed

    Everaert, Inge; Mooyaart, Antien; Baguet, Audrey; Zutinic, Ana; Baelde, Hans; Achten, Eric; Taes, Youri; De Heer, Emile; Derave, Wim

    2011-04-01

    Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and 55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively related to the subjects' age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of β-alanine. Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism, female gender and increasing age are the factors associated with reduced muscle carnosine stores. PMID:20865290

  19. Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury.

    PubMed

    Woo, Anthony Y H; Waye, Mary M Y; Tsui, Stephen K W; Yeung, Sandy T W; Cheng, Christopher H K

    2008-04-01

    Recent studies revealed that the herb Andrographis paniculata possesses cardioprotective activities. Using neonatal rat cardiomyocytes, the cardioprotective actions of several diterpene lactones derived from A. paniculata including andrographolide, 14-deoxyandrographolide, 14-deoxy-11,12-didehydroandrographolide, and sodium 14-deoxyandrographolide-12-sulfonate were investigated. Pretreatment with andrographolide but not with the other compounds protected the cardiomyocytes against hypoxia/ reoxygenation injury and up-regulated the cellular-reduced glutathione (GSH) level and antioxidant enzyme activities. The cardioprotective action of andrographolide was found to coincide in a time-dependent manner with the up-regulation of GSH, indicating the important role of GSH. The cardioprotective action of andrographolide was also completely abolished by buthionine sulfoximine, which acts as a specific gamma-glutamate cysteine ligase (GCL) inhibitor to deplete cellular GSH level. It was subsequently found that the mRNA and protein levels of the GCL catalytic subunit (GCLC) and modifier subunit (GCLM) were up-regulated by andrographolide. Luciferase reporter assay also demonstrated that andrographolide activated both the GCLC and the GCLM promoters in the transfected rat H9C2 cardiomyocyte cell line. The 12-O-tetradecanoylphorbo-13-acetate response element or the antioxidant response element may be involved in the transactivating actions of andrographolide on the GCLC and GCLM promoters. The present study pinpoints andrographolide as a cardioprotective principle in A. paniculata and reveals its cytoprotective mechanism. PMID:18174384

  20. 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.

  1. Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

    PubMed

    Pontes, Thaís Brilhante; Chen, Elizabeth Suchi; Gigek, Carolina Oliveira; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Leal, Mariana Ferreira; Demachki, Samia; Assumpção, Paulo Pimentel; Artigiani, Ricardo; Lourenço, Laércio Gomes; Burbano, Rommel Rodriguez; Arruda Cardoso Smith, Marília

    2014-04-01

    Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia. PMID:24338710

  2. Ceramides and cell signaling molecules in psoriatic epidermis: reduced levels of ceramides, PKC-alpha, and JNK.

    PubMed

    Lew, Bark-Lynn; Cho, Yunhi; Kim, Jungmin; Sim, Woo-Young; Kim, Nack-In

    2006-02-01

    Ceramides are the main lipids in the stratum corneum and are generated during cellular stress and apoptosis by de novo synthesis or by the action of sphingomyelinase. In addition, they are lipid second messengers produced by sphingolipid metabolism and trigger important cell responses, including protein kinase C-alpha (PKC-alpha) activation and the stimulation of signal transduction pathways with apoptosis and stress-activated protein kinases (SAPK), such as c-jun N-terminal kinase (JNK). Thus, ceramides have anti-proliferative and apoptotic effects. This study measured the changes in the levels of epidermal ceramides and ceramide-related apoptotic signaling molecules in psoriasis patients. Samples from lesional and non-lesional epidermis were obtained from psoriasis patients. Total ceramides were fractionated using thin-layer chromatography, and the levels of PKC-alpha and JNK expression were measured using Western blot analysis with specific antibodies. The ceramide level was reduced significantly, and this was associated with the downregulation of apoptotic signaling molecules, such as PKC-alpha and JNK, in the lesional epidermis of psoriasis patients. These results suggest that the decreased level of ceramides downregulates the apoptotic pathway, leading to epidermal proliferation in psoriasis. PMID:16479073

  3. 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.

  4. 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

  5. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Astrophysics Data System (ADS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; McCollum, T.; Anzic, J.

    1992-11-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  6. Probiotic treatment reduces appetite and glucose level in the zebrafish model

    PubMed Central

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  7. Probiotic treatment reduces appetite and glucose level in the zebrafish model.

    PubMed

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  8. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, K. K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept for enhancing the lifetime of materials in low Earth orbits is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  9. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  10. Sodium salicylate reduces the level of GABAB receptors in the rat's inferior colliculus.

    PubMed

    Butt, S; Ashraf, F; Porter, L A; Zhang, H

    2016-03-01

    Previous studies have indicated that sodium salicylate (SS) can cause hearing abnormalities through affecting the central auditory system. In order to understand central effects of the drug, we examined how a single intraperitoneal injection of the drug changed the level of subunits of the type-B γ-aminobutyric acid receptor (GABAB receptor) in the rat's inferior colliculus (IC). Immunohistochemical and western blotting experiments were conducted three hours following a drug injection, as previous studies indicated that a tinnitus-like behavior could be reliably induced in rats within this time period. Results revealed that both subunits of the receptor, GABABR1 and GABABR2, reduced their level over the entire area of the IC. Such a reduction was observed in both cell body and neuropil regions. In contrast, no changes were observed in other brain structures such as the cerebellum. Thus, a coincidence existed between a structure-specific reduction in the level of GABAB receptor subunits in the IC and the presence of a tinnitus-like behavior. This coincidence likely suggests that a reduction in the level of GABAB receptor subunits was involved in the generation of a tinnitus-like behavior and/or used by the nervous system to restore normal hearing following application of SS. PMID:26705739

  11. 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

  12. 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

  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. Ultraviolet-ozone treatment reduces levels of disease-associated prion protein and prion infectivity

    USGS Publications Warehouse

    Johnson, C.J.; Gilbert, P.; McKenzie, D.; Pedersen, J.A.; Aiken, Judd M.

    2009-01-01

    Background. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases caused by novel infectious agents referred to as prions. Prions appear to be composed primarily, if not exclusively, of a misfolded isoform of the cellular prion protein. TSE infectivity is remarkably stable and can resist many aggressive decontamination procedures, increasing human, livestock and wildlife exposure to TSEs. Findings. We tested the hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein and inactivates the infectious agent. We found that UV-ozone treatment decreased the carbon and prion protein content in infected brain homogenate to levels undetectable by dry-ashing carbon analysis or immunoblotting, respectively. After 8 weeks of ashing, UV-ozone treatment reduced the infectious titer of treated material by a factor of at least 105. A small amount of infectivity, however, persisted despite UV-ozone treatment. When bound to either montmorillonite clay or quartz surfaces, PrPTSE was still susceptible to degradation by UV-ozone. Conclusion. Our findings strongly suggest that UV-ozone treatment can degrade pathogenic prion protein and inactivate prions, even when the agent is associated with surfaces. Using larger UV-ozone doses or combining UV-ozone treatment with other decontaminant methods may allow the sterilization of TSE-contaminated materials. ?? 2009 Aiken et al; licensee BioMed Central Ltd.

  15. Apolipoprotein AI levels are increased in part as a consequence of reduced catabolism in nephrotic rats.

    PubMed

    Kaysen, G A; Hoye, E; Jones, H

    1995-03-01

    Apolipoprotein AI (apo AI) synthesis, measured as the turnover of 125I-labeled apo AI-labeled high-density lipoprotein (HDL), was increased significantly in rats with Heymann nephritis (HN) vs. control Sprague-Dawley (SD) rats. However, fractional apo AI catabolic rate was also significantly less in HN vs. SD. We used 125I-apo AI tyramine cellobiose HDL, a marker retained at the catabolic site, to establish where apo AI catabolism decreased in six HN rats, seven rats with adriamycin (Adria)-induced nephrosis, and six control SD. Total renal apo AI catabolism, plus urinary losses, were the same in all three groups, despite significant urinary apo AI in HN and Adria rats. Apo AI catabolism was reduced in skin in both nephrotic groups, accounting for approximately 44% of reduced in apo AI catabolism. Thus a significant fraction of apo AI is catabolized in skin of normal male rats. Reduced apo AI catabolism in skin contributes to increased plasma levels in nephrotic rats. PMID:7900854

  16. Quinolizidine alkaloids reduced mortality in EV71-infected mice by compensating for the levels of T cells.

    PubMed

    Yang, Yajun; Guan, Feifei; Bai, Lin; Zhang, Li; Liu, Jiangning; Pan, Xiandao; Zhang, Lianfeng

    2015-09-01

    Recent outbreak of hand, foot and mouse disease caused by enterovirus 71 is a serious threat to infants and children in Asia-Pacific countries. No vaccines or antiviral therapies are available against this infection. In this study, we found that quinolizidine alkaloids could improve the levels of T cells in mice. The structure-activity relationships demonstrated that the oxidation and double bonds are important for the excellent potency. Oxysophocarpine, the most effective compound of six quinolizidine alkaloids, could also relieve symptoms and reduce mortality in lethal enterovirus 71-infected mice through compensating for the decreased levels of T cells. This work suggested that quinolizidine alkaloids have the potential against enterovirus 71 for further development of novel antiviral drugs. PMID:26189894

  17. 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

  18. 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

  19. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress

    PubMed Central

    Saliba, Flávia G.; Adiwardana, Natanael S.; Uehara, Eliane U.; Silvestre, Renata N.; Leite, Victor V.; Faleiros, Francisca T.V.; Padovani, Flávia H.P.; De Gobbi, Juliana I.F.

    2016-01-01

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  20. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress.

    PubMed

    Saliba, Flávia G; Adiwardana, Natanael S; Uehara, Eliane U; Silvestre, Renata N; Leite, Victor V; Faleiros, Francisca T V; Padovani, Flávia H P; De Gobbi, Juliana I F

    2016-03-31

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  1. A heuristic re-mapping algorithm reducing inter-level communication in SAMR applications.

    SciTech Connect

    Steensland, Johan; Ray, Jaideep

    2003-07-01

    This paper aims at decreasing execution time for large-scale structured adaptive mesh refinement (SAMR) applications by proposing a new heuristic re-mapping algorithm and experimentally showing its effectiveness in reducing inter-level communication. Tests were done for five different SAMR applications. The overall goal is to engineer a dynamically adaptive meta-partitioner capable of selecting and configuring the most appropriate partitioning strategy at run-time based on current system and application state. Such a metapartitioner can significantly reduce execution times for general SAMR applications. Computer simulations of physical phenomena are becoming increasingly popular as they constitute an important complement to real-life testing. In many cases, such simulations are based on solving partial differential equations by numerical methods. Adaptive methods are crucial to efficiently utilize computer resources such as memory and CPU. But even with adaption, the simulations are computationally demanding and yield huge data sets. Thus parallelization and the efficient partitioning of data become issues of utmost importance. Adaption causes the workload to change dynamically, calling for dynamic (re-) partitioning to maintain efficient resource utilization. The proposed heuristic algorithm reduced inter-level communication substantially. Since the complexity of the proposed algorithm is low, this decrease comes at a relatively low cost. As a consequence, we draw the conclusion that the proposed re-mapping algorithm would be useful to lower overall execution times for many large SAMR applications. Due to its usefulness and its parameterization, the proposed algorithm would constitute a natural and important component of the meta-partitioner.

  2. Mediators Affecting Girls’ Levels of Physical Activity Outside of School: Findings from the Trial of Activity in Adolescent Girls

    PubMed Central

    Lytle, Leslie A.; Murray, David M.; Evenson, Kelly R.; Moody, Jamie; Pratt, Charlotte A.; Metcalfe, Lauve; Parra-Medina, Deborah

    2010-01-01

    Background Providing after school activities is a community level approach for reducing the decline in physical activity of girls as they reach early adolescence. Purpose The purpose of this study was to examine psychosocial, environmental, and behavioral factors as potential mediators of after school physical activity in adolescent girls. Methods We assessed objectively measured levels of physical activity occurring outside of school and potential predictors and mediators of activity in girls participating in the Trial of Activity in Adolescent Girls (TAAG). Results We found that the TAAG intervention had a statistically significant and positive effect on out of school activity in the 2006 cohort. Self-efficacy, friends’ social support, total social support, and difficulty getting to and from community activities mediated the level of moderate to vigorous physical activity in girls. Conclusions Parents, communities, and schools should provide and enhance opportunities outside of the school day for adolescents to be active. Reducing transportation barriers and enlisting social support appear to be key. PMID:20012810

  3. Isolation of a Fusarium solani mutant reduced in cutinase activity and virulence.

    PubMed Central

    Dantzig, A H; Zuckerman, S H; Andonov-Roland, M M

    1986-01-01

    Fusarium solani isolate T-8 produces an extracellular enzyme, cutinase, which catalyzes the degradation of cutin in the plant cuticle. Cutinase activity can be measured by the hydrolysis of either the artifical substrate, p-nitrophenylbutyrate (PNB), or radioactive cutin containing [14C]palmitic acid. In the present study, the culture filtrate contained basal levels of cutinase when T-8 was grown on acetate as a sole source of carbon. After mutagenesis, a cutinase-defective mutant (PNB-1) was identified by screening acetate-grown colonies for a loss of PNBase activity. The mutant possessed an 80 to 90% reduction in cutinase activity when grown for 3 to 5 days on acetate- or cutin-containing medium. Induction of cutinase by cutin or hydrolyzed cutin after growth on glucose medium was similarly reduced. Kinetic analysis indicated that cutinase from the mutant possessed a near normal Km for PNB and a 92% reduction in Vmax. Fluorography and Western blotting of 15% sodium dodecyl sulfate-polyacrylamide gels of separated 35S-labeled proteins from cutin induction medium revealed that in the mutant the 22,000-molecular-weight band corresponding to cutinase was reduced approximately 85%. The virulence of the mutant in a pea stem bioassay was decreased by 55% and was restored to nearly the parental level by the addition of purified cutinase. The data suggest that the mutant synthesizes reduced quantities of a functional and immunoreactive cutinase enzyme and that cutinase plays a critical role in infection. The PNB1 mutation may be within a regulatory gene or a promoter for cutinase. Images PMID:3782031

  4. 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.

  5. Characterization of Triosephosphate Isomerase Mutants with Reduced Enzyme Activity in Mus Musculus

    PubMed Central

    Merkle, S.; Pretsch, W.

    1989-01-01

    Four heterozygous triosephosphate isomerase (TPI) mutants with approximately 50% reduced activity in blood compared to wild type were detected in offspring of 1-ethyl-1-nitrosourea treated male mice. Breeding experiments displayed an autosomal, dominant mode of inheritance for the mutations. All mutations were found to be homozygous lethal at an early postimplantation stage of embryonic development, probably due to a total lack of TPI activity and consequently to the inability to utilize glucose as a source of metabolic energy. Although activity alteration was also found in liver, lung, kidney, spleen, heart, brain and muscle the TPI deficiency in heterozygotes has no influence on the following physiological traits: hematological parameters, plasma glucose, glucose consumption of blood cells, body weight and organo-somatic indices of liver, spleen, heart, kidney and lung. Biochemical investigations of TPI in the four mutant lines indicated no difference of physicochemical properties compared to the wild type. Results from immunoinactivation assays indicate that the decrease of enzyme activity corresponds to a decrease in the level of an immunologically active moiety. It is suggested that the mutations have affected the Tpi-1 structural locus and resulted in alleles which produce no detectable enzyme activity and no immunologically cross-reacting material. The study furthermore suggests one functional TPI gene per haploid genome in the erythrocyte and seven other tested organs of the mouse. PMID:2693209

  6. 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.

  7. 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

  8. Attenuation of virulence in an apicomplexan hemoparasite results in reduced genome diversity at the population level

    PubMed Central

    2011-01-01

    Background Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background. Results Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains. Conclusions This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus. PMID:21838895

  9. Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease.

    PubMed

    Cebotaru, Liudmila; Liu, Qiangni; Yanda, Murali K; Boinot, Clement; Outeda, Patricia; Huso, David L; Watnick, Terry; Guggino, William B; Cebotaru, Valeriu

    2016-07-01

    Abnormal proliferation of cyst-lining epithelium and increased intracystic fluid secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) are thought to contribute to cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Histone deacetylase 6 (HDAC6) expression and activity are increased in certain cancers, neurodegenerative diseases, and in Pkd1-mutant renal epithelial cells. Inhibition of HDAC6 activity with specific inhibitors slows cancer growth. Here we studied the effect of tubacin, a specific HDAC6 inhibitor, on cyst growth in polycystic kidney disease. Treatment with tubacin prevented cyst formation in MDCK cells, an in vitro model of cystogenesis. Cyclic AMP stimulates cell proliferation and activates intracystic CFTR-mediated chloride secretion in ADPKD. Treatment with tubacin downregulated cyclic AMP levels, inhibited cell proliferation, and inhibited cyclic AMP-activated CFTR chloride currents in MDCK cells. We also found that tubacin reduced cyst growth by inhibiting proliferation of cyst-lining epithelial cells, downregulated cyclic AMP levels, and improved renal function in a Pkd1-conditional mouse model of ADPKD. Thus, HDAC6 could play a role in cyst formation and could serve as a potential therapeutic target in ADPKD. PMID:27165822

  10. Diagnostic accuracy at several reduced radiation dose levels for CT imaging in the diagnosis of appendicitis

    NASA Astrophysics Data System (ADS)

    Zhang, Di; Khatonabadi, Maryam; Kim, Hyun; Jude, Matilda; Zaragoza, Edward; Lee, Margaret; Patel, Maitraya; Poon, Cheryce; Douek, Michael; Andrews-Tang, Denise; Doepke, Laura; McNitt-Gray, Shawn; Cagnon, Chris; DeMarco, John; McNitt-Gray, Michael

    2012-03-01

    Purpose: While several studies have investigated the tradeoffs between radiation dose and image quality (noise) in CT imaging, the purpose of this study was to take this analysis a step further by investigating the tradeoffs between patient radiation dose (including organ dose) and diagnostic accuracy in diagnosis of appendicitis using CT. Methods: This study was IRB approved and utilized data from 20 patients who underwent clinical CT exams for indications of appendicitis. Medical record review established true diagnosis of appendicitis, with 10 positives and 10 negatives. A validated software tool used raw projection data from each scan to create simulated images at lower dose levels (70%, 50%, 30%, 20% of original). An observer study was performed with 6 radiologists reviewing each case at each dose level in random order over several sessions. Readers assessed image quality and provided confidence in their diagnosis of appendicitis, each on a 5 point scale. Liver doses at each case and each dose level were estimated using Monte Carlo simulation based methods. Results: Overall diagnostic accuracy varies across dose levels: 92%, 93%, 91%, 90% and 90% across the 100%, 70%, 50%, 30% and 20% dose levels respectively. And it is 93%, 95%, 88%, 90% and 90% across the 13.5-22mGy, 9.6-13.5mGy, 6.4-9.6mGy, 4-6.4mGy, and 2-4mGy liver dose ranges respectively. Only 4 out of 600 observations were rated "unacceptable" for image quality. Conclusion: The results from this pilot study indicate that the diagnostic accuracy does not change dramatically even at significantly reduced radiation dose.

  11. 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

  12. Immunization with recombinant Pb27 protein reduces the levels of pulmonary fibrosis caused by the inflammatory response against Paracoccidioides brasiliensis.

    PubMed

    Morais, Elis Araujo; Martins, Estefânia Mara do Nascimento; Boelone, Jankerle Neves; Gomes, Dawidson Assis; Goes, Alfredo Miranda

    2015-02-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis in which the host response to the infectious agent typically consists of a chronic granulomatous inflammatory process. This condition causes lesions that impair lung function and lead to chronic pulmonary insufficiency resulting from fibrosis development, which is a sequel and disabling feature of the disease. The rPb27 protein has been studied for prophylactic and therapeutic treatment against PCM. Previous studies from our laboratory have shown a protective effect of rPb27 against PCM. However, these studies have not determined whether rPb27 immunization prevents lung fibrosis. We therefore conducted this study to investigate fibrosis resulting from infection by Paracoccidioides brasiliensis in the lungs of animals immunized with rPb27. Animals were immunized with rPb27 and subsequently infected with a virulent strain of P. brasiliensis. Fungal load was evaluated by counting colony-forming units, and Masson's trichrome staining was performed to evaluate fibrosis at 30 and 90 days post-infection. The levels of CCR7, active caspase 3, collagen and cytokines were analyzed. At the two time intervals mentioned, the rPb27 group showed lower levels of fibrosis on histology and reduced levels of collagen and the chemokine receptor CCR7 in the lungs. CCR7 was detected at higher levels in the control groups that developed very high levels of pulmonary fibrosis. Additionally, the immunized groups showed high levels of active caspase 3, IFN-γ, TGF-β and IL-10 in the early phase of P. brasiliensis infection. Immunization with Pb27, in addition to its protective effect, was shown to prevent pulmonary fibrosis. PMID:25487973

  13. Predicting preferred coring level to reduce toner scatter in electrophotographic printing

    NASA Astrophysics Data System (ADS)

    Park, Hyung Jun; Allebach, Jan P.

    2011-01-01

    The electrophotographic process depends on a complex interplay between electrostatically charged toner particles, the developer roller, and the organic photoconductor during development; and between the toner particles, the organic photoconductor, and the paper during transfer. The task of controlling the imaging process is made even more challenging by the fact that colorant planes are developed independently and in succession. At high colorant levels, toner particles for a given colorant plane may be strongly repelled by toner that has already been deposited for previously developed colorant planes. The result is scattering of toner away from the edges of thin lines and character strokes. In previous work, we have proposed a coring method to reduce the occurrence of the toner scatter, and conducted psychophysical experiments to determine the preferred level of coring as a function of line width and colorant level. In this paper, we apply the edge transition width (ETW) metric to physically measure the impact of toner scatter on the sharpness of edges of lines and character strokes. We consider ETW both with and without coring, and compare it to the results from our earlier psychophysical experiments.

  14. Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

    NASA Astrophysics Data System (ADS)

    Paiva-Oliveira, E. L.; Lima, N. C.; Silva, P. H.; Sousa, N. T. A.; Barbosa, F. S.; Orsini, M.; Silva, J. G.

    2012-09-01

    Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control ( p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group ( p < 0.01). Collagen deposition was significantly increased in the final stages of regeneration at test group, when compared with control group ( p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.

  15. Movement Activity Levels on Traditional and Contemporary Playground Structures.

    ERIC Educational Resources Information Center

    Gabbard, Carl P.; LeBlanc, Elizabeth

    This study investigated playground activity levels of children in grades K-4 and compared levels of use of traditional and creative playground apparatus. The traditional playground area consisted of climbing bars, slides, ladders, chin bars, swings, see saws, and a merry-go-round. The creative playground contained tire hurdles, tire walk, tire…

  16. Physical Activity Levels in Portuguese High School Physical Education

    ERIC Educational Resources Information Center

    Marmeleira, Jose Francisco Filipe; Aldeias, Nuno Micael Carrasqueira; da Graca, Pedro Miguel dos Santos Medeira

    2012-01-01

    The main aim of this study was to evaluate the physical activity (PA) levels of high school Portuguese students during physical education (PE) and investigate the association of PA levels with students' goal orientation and intrinsic motivation. Forty-six students from three high schools participated. Heart rate telemetry and pedometry were used…

  17. 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

  18. Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants

    PubMed Central

    Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

    2016-01-01

    Introduction Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Materials and Methods Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. Results At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Conclusion Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the

  19. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

    PubMed

    Isidori, A M; Caprio, M; Strollo, F; Moretti, C; Frajese, G; Isidori, A; Fabbri, A

    1999-10-01

    Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced

  20. Active Ageing Level of Older Persons: Regional Comparison in Thailand

    PubMed Central

    Haque, Md. Nuruzzaman

    2016-01-01

    Active ageing level and its discrepancy in different regions (Bangkok, Central, North, Northeast, and South) of Thailand have been examined for prioritizing the policy agenda to be implemented. Attempt has been made to test preliminary active ageing models for Thai older persons and hence active ageing index (AAI, ranges from 0 to 1) has been estimated. Using nationally representative data and confirmatory factor analysis approach, this study justified active ageing models for female and male older persons in Thailand. Results revealed that active ageing level of Thai older persons is not high (mean AAIs for female and male older persons are 0.64 and 0.61, resp., and those are significantly different (p < 0.001)). Mean AAI in Central region is lower than North, Northeast, and South regions but there is no significant difference in the latter three regions of Thailand. Special emphasis should be given to Central region and policy should be undertaken for increasing active ageing level. Implementation of an Integrated Active Ageing Package (IAAP), containing policies for older persons to improve their health and economic security, to promote participation in social groups and longer working lives, and to arrange learning programs, would be helpful for increasing older persons' active ageing level in Thailand. PMID:27375903

  1. Seasonality in Children's Pedometer-Measured Physical Activity Levels

    ERIC Educational Resources Information Center

    Beighle, Aaron; Alderman, Brandon; Morgan, Charles F.; Le Masurier, Guy

    2008-01-01

    Seasonality appears to have an impact on children's physical activity levels, but equivocal findings demand more study in this area. With the increased use of pedometers in both research and practice, collecting descriptive data in various seasons to examine the impact of seasonality on pedometer-measured physical activity among children is…

  2. African American Preschool Children's Physical Activity Levels in Head Start

    ERIC Educational Resources Information Center

    Shen, Bo; Reinhart-Lee, Tamara; Janisse, Heather; Brogan, Kathryn; Danford, Cynthia; Jen, K-L. C.

    2012-01-01

    The purpose of this study was to describe the physical activity levels of urban inner city preschoolers while attending Head Start, the federally funded preschool program for children from low-income families. Participants were 158 African American children. Their physical activity during Head Start days was measured using programmed RT-3…

  3. The Role of Various Curriculum Models on Physical Activity Levels

    ERIC Educational Resources Information Center

    Culpepper, Dean O.; Tarr, Susan J.; Killion, Lorraine E.

    2011-01-01

    Researchers have suggested that physical education curricula can be highly effective in increasing physical activity levels at school (Sallis & Owen, 1999). The purpose of this study was to investigate the impact of various curriculum models on physical activity. Total steps were measured on 1,111 subjects and three curriculum models were studied…

  4. Postmenopausal vegetarians' low serum ferritin level may reduce the risk for metabolic syndrome.

    PubMed

    Kim, Mi-Hyun; Bae, Yun Jung

    2012-10-01

    The present study was conducted to compare the serum ferritin status between the postmenopausal vegetarians and non-vegetarians and to identify the relation of serum ferritin with metabolic syndrome (MetS) risk factors in postmenopausal women. The two study groups consisted of postmenopausal vegetarians (n=59) who maintained a vegetarian diet for over 20 years and age-matched non-vegetarian controls (n=48). Anthropometric measurements, dietary intakes, serum metabolic syndrome-related parameters, and serum ferritin level between the two groups were compared. The vegetarians exhibited significantly lower weight (p<0.01), body mass index (BMI) (p<0.001), percentage of body fat (p<0.001), waist circumference (p<0.01), SBP (p<0.001), DBP (p<0.001), and fasting glucose (p<0.05). According to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III criteria for MetS applying Korean guidelines for waist circumference, the prevalence of MetS was lower in vegetarians (33.9 %) than in non-vegetarians (47.9 %). Vegetarians had significantly lower serum level of ferritin (p<0.01) than non-vegetarians. In the correlation analysis, serum ferritin was positively related to fasting glucose (r=0.264, p<0.01), triglycerides (r=0.232, p<0.05), and the NCEP score (r=0.214, p<0.05) and negatively related to high-density lipoprotein-cholesterol (r=-0.225, p<0.05) after adjusting for BMI, lifestyle, and dietary factors (animal protein, animal fat, and dietary fiber intake). In conclusion, postmenopausal vegetarians had lower MetS presence and a lower serum ferritin level compared to non-vegetarians. Furthermore, vegetarians' low serum ferritin level may reduce the risk of MetS in postmenopausal women. PMID:22528775

  5. Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension.

    PubMed

    Zhang, Y-Y; Tong, X-Z; Xia, W-H; Xie, W-L; Yu, B-B; Zhang, B; Chen, L; Tao, J

    2016-07-01

    Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension: r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63±0.17 versus 0.50±0.19, P=0.001), whereas arterial elasticity (baPWV: 1764±101 versus 1685±96 cm s(-1), P=0.272) and endothelial function (FMD: 5.92±1.43% versus 7.73±1.31%, P<0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension. PMID

  6. Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration.

    PubMed

    Chiang, Huei-Hsin; Forsell, Charlotte; Lilius, Lena; Öijerstedt, Linn; Thordardottir, Steinunn; Shanmugarajan, Krishnan; Westerlund, Marie; Nennesmo, Inger; Thonberg, Håkan; Graff, Caroline

    2013-11-01

    Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease with an age at onset generally below 65 years. Mutations in progranulin (GRN) have been reported to be able to cause FTLD through haploinsufficiency. We have sequenced GRN in 121 patients with FTLD and detected six different mutations in eight patients: p.Gly35Glufs*19, p.Asn118Phefs*4, p.Val200Glyfs*18, p.Tyr294*, p.Cys404* and p.Cys416Leufs*30. Serum was available for five of the mutations, where the serum-GRN levels were found to be >50% reduced compared with FTLD patients without GRN mutations. Moreover, the p.Cys416Leufs*30 mutation segregated in an affected family with different dementia diagnoses. The mutation frequency of GRN mutation was 6.6% in our FTLD cohort. PMID:23463024

  7. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities.

    PubMed

    Chen, Jie; Mullins, C Daniel; Novak, Priscilla; Thomas, Stephen B

    2016-02-01

    Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and self-determination for their own health and health care. We propose a patient-centered, multilevel activation and empowerment framework (individual-, health care professional-, community-, and health care delivery system-level) to inform the development of culturally informed personalized patient activation and empowerment (P-PAE) interventions to improve population health and reduce racial and ethnic disparities. We discuss relevant Affordable Care Act payment and delivery policy reforms and how they affect patient activation and empowerment. Such policies include Accountable Care Organizations and value-based purchasing, patient-centered medical homes, and the community health benefit. Challenges and possible solutions to implementing the P-PAE are discussed. Comprehensive and longitudinal data sets with consistent P-PAE measures are needed to conduct comparative effectiveness analyses to evaluate the optimal P-PAE model. We believe the P-PAE model is timely and sustainable and will be critical to engaging patients in their treatment, developing patients' abilities to manage their health, helping patients express concerns and preferences regarding treatment, empowering patients to ask questions about treatment options, and building up strategic patient-provider partnerships through shared decision making. PMID:25845376

  8. 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.

  9. U.S. commitments and responsibilities to reduce global warmings: Contributions of state-level policies and programs

    SciTech Connect

    Wilt, C.A.; Feldman, D.L.

    1995-12-01

    Global warming is one of the most contentious and complex environmental issues confronting scientists and public policy makers. The scope and potential impacts of global warming are immense, affecting virtually all natural processes at many levels, including coastal zone erosion, estuarine habitat, forests, and agriculture. We hypothesize that managing the natural and societal impacts of global warming, including the costs of its management, abatement, and adaptation, requires not only the cooperation of international agencies and national government, but of individual states and provinces as well. There has been a considerable increase in state-level activity to reduce global warming in the United States, but there has been little assessment of its extent or state motivations. This paper will provide an overview of possible U.S. states` commitments and responsibilities under international treaties and agreements, as well as national policy decrees such as the Clinton Administrations` Climate Change Action Plan. A review of current states` activities with brief case studies of the more progressive state programs (Connecticut, Iowa, California, Missouri, Oregon), their achievements, and their significance. We focus upon federally-mandated global change activities imposed upon states (e.g., national regulations to conserve energy or reduce emissions) and state-motivated policies not required by any national regulation (e.g., land use, transportation, regional planning policies with impacts on global change.) The latter policies may be aimed specifically at global warming prevention or mitigation or they may be incidental, beneficial by-products of policies intended for other purposes--so called `no regrets` policies. We compare the performance of state policies in these two categories in order to ascertain their relative effectiveness and promise for addressing climate change problems.

  10. PPAR-γ agonist stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination

    SciTech Connect

    Sun, Yan; Zheng, Bin; Zhang, Xin-hua; He, Ming; Guo, Zong-wei; Wen, Jin-kun

    2014-01-10

    Highlights: •PPAR-γ increases KLF4 protein level but does not influence KLF4 gene transcription. •The increase of KLF4 protein levels induced by pioglitazone is PPAR-γ-dependent. •Pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination. -- Abstract: Peroxisome proliferator activated receptor γ (PPAR-γ) plays important roles in cell cycle regulation, differentiation and apoptosis. Krüppel-like factor 4 (KLF4) modulates vascular smooth muscle cell (VSMC) phenotype. Both KLF4 and PPAR-γ are involved in VSMC proliferation and differentiation. However, the actual relationship between KLF4 and PPAR-γ in VSMCs is not clear. In this study, we found that PPAR-γ agonist pioglitazone increases KLF4 protein levels but does not influence KLF4 gene transcription. PPAR-γ overexpression increases, while PPAR-γ knockdown reduces KLF4 expression, suggesting that the increase in KLF4 protein levels induced by pioglitazone is PPAR-γ-dependent. Further study showed that pioglitazone enhances KLF4 protein stability through reducing KLF4 ubiquitination. Furthermore, we demonstrated that stabilization of KLF4 by pioglitazone was related to the activation of Akt signaling pathway. Taken together, we revealed that PPAR-γ agonist pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination, providing further insights into PPAR-γ and KLF4 in regulating each other’s expression in VSMCs.

  11. Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat.

    PubMed

    Batta, Ashok K; Xu, Guorong; Honda, Akira; Miyazaki, Teruo; Salen, Gerald

    2006-03-01

    Plant sterols compete with cholesterol (cholest-5-en-3beta-ol) for intestinal absorption to limit absorption and lower plasma concentrations of cholesterol. Stigmasterol (24-ethyl-cholesta-5,22-dien-3beta-ol; Delta(22) derivative of sitosterol [24-ethyl-cholest-5-en-3beta-ol]), but not campesterol (24-methyl-cholest-5-en-3beta-ol) and sitosterol, is reported to inhibit cholesterol biosynthesis via inhibition of sterol Delta(24)-reductase in human Caco-2 and HL-60 cell lines. We studied the effect of feeding 0.5% stigmasterol on plasma and liver sterols and intestinal cholesterol and sitosterol absorption in 12 wild-type Kyoto (WKY) and 12 Wistar rats. After 3 weeks of feeding, cholesterol and sitosterol absorption was determined in 6 rats from each group by plasma dual-isotope ratio method. After 3 more weeks, plasma and hepatic sterols and hepatic enzyme activities were determined in all rats. After feeding stigmasterol, baseline plasma cholesterol was 1.3 times and plant sterols 3 times greater in WKY compared with Wistar rats. Stigmasterol feeding lowered plasma cholesterol by approximately 11%, whereas plasma campesterol and sitosterol levels were virtually unchanged in both rat strains, and stigmasterol constituted 3.2% of plasma sterols in WKY rats and 1% in Wistar rats. After 6 weeks of feeding, cholesterol and sitosterol absorption decreased 23% and 30%, respectively, in WKY, and 22% and 16%, respectively, in the Wistar rats as compared with untreated rats. The intestinal bacteria in both rat strains metabolized stigmasterol to mainly the 5beta-H stanol (>40%), with only small amounts of 5alpha-H derivative (approximately 1.5%), whereas the C-22 double bond was resistant to bacterial metabolism. Hepatic stigmasterol levels increased from 11 microg/g liver tissue to 104 mug/g in WKY rats and from 5 microg/g liver tissue to 21 microg/g in Wistar rats. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was suppressed 4-fold in the WKY and almost 1.8-fold

  12. 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

  13. Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

    NASA Technical Reports Server (NTRS)

    Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

  14. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  15. Low level laser therapy reduces oxidative stress in cortical neurons in vitro

    NASA Astrophysics Data System (ADS)

    Huang, Ying-Ying; Tedford, Clark E.; McCarthy, Thomas; Hamblin, Michael R.

    2012-03-01

    It is accepted that the mechanisms of low level laser therapy (LLLT) involves photons that are absorbed in the mitochondria of cells and lead to increase of mitochondrial metabolism resulting in more electron transport, increase of mitochondrial membrane potential, and more ATP production. Intracellular calcium changes are seen that correlate with mitochondrial stimulation. The situation with two other intermediates is more complex however: reactive oxygen species (ROS) and nitric oxide (NO). Evidence exists that low levels of ROS are produced by LLLT in normal cells that can be beneficial by (for instance) activating NF-kB. However high fluences of light can produce large amounts of ROS that can damage the cells. In oxidatively stressed cells the situation may be different. We exposed primary cultured cortical neurons to hydrogen peroxide (H2O2) or cobalt chloride (CoCl2) oxidative insults in the presence or absence of LLLT (810-nm laser at 0.3 or 3 J/cm2). Cell viability of cortical neurons was determined by lactate dehydrogenase assay. ROS in neurons was detected using an ROS probe, MitoRox with confocal microscopy. Results showed that LLLT dose-dependently reversed ROS production and protected cortical neurons against H2O2 or CoCl2 induced oxidative injury in cultured cortical neurons. Conclusion: LLLT can protect cortical neurons against oxidative stress by reversing the levels of ROS.

  16. 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

  17. Physical Activity Level and Physical Functionality in Nonagenarians Compared to Individuals Aged 60–74 Years

    PubMed Central

    Frisard, Madlyn I.; Fabre, Jennifer M.; Russell, Ryan D.; King, Christina M.; DeLany, James P.; Wood, Robert H.; Ravussin, Eric

    2009-01-01

    Background Functional dependence and the risks of disability increase with age. The loss of independence is thought to be partially due to a decrease in physical activity. However, in populations, accurate measurement of physical activity is challenging and may not provide information on functional impairment. Methods This study therefore assessed physical functionality and physical activity level in a group of nonagenarians (11 men/11 women; 93 ± 1 years, 66.6 ± 2.4 kg, body mass index [BMI] = 24 ± 1 kg/m2) and a group of participants aged 60–74 years (17 men/15 women; 70 ± 1 years, 83.3 ± 3.0 kg, BMI = 29 ± 1 kg/m2) from the Louisiana Healthy Aging Study. Physical activity level was calculated from total energy expenditure (TEE) and resting metabolic rate (RMR). Physical functionality was assessed using the Reduced Continuous Scale Physical Functional Performance Test (CS-PFP10). Results Nonagenarians had lower absolute ( p < .001) and adjusted ( p < .007) TEE compared to participants aged 60–74 years which was attributed to a reduction in both RMR and physical activity level. Nonagenarians also had reduced functional performance ( p < .001) which was correlated with activity level (r = 0.68, p < .001). Conclusions When compared to individuals aged 60–74 years, 73% of the reduction in TEE in nonagenarians can be attributed to a reduction in physical activity level, the remaining being accounted for by a reduction in RMR. The reduced physical activity in nonagenarians is associated with less physical functionality. This study provides the first objective comparison of physical functionality and actual levels of physical activity in older individuals. PMID:17634327

  18. Automated concept-level information extraction to reduce the need for custom software and rules development

    PubMed Central

    Nguyen, Thien M; Goryachev, Sergey; Fiore, Louis D

    2011-01-01

    Objective Despite at least 40 years of promising empirical performance, very few clinical natural language processing (NLP) or information extraction systems currently contribute to medical science or care. The authors address this gap by reducing the need for custom software and rules development with a graphical user interface-driven, highly generalizable approach to concept-level retrieval. Materials and methods A ‘learn by example’ approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations. The Fourth i2b2/VA Shared Task Challenge's concept extraction task provided the data sets and metrics used to evaluate performance. Results Top F-measure scores for each of the tasks were medical problems (0.83), treatments (0.82), and tests (0.83). Recall lagged precision in all experiments. Precision was near or above 0.90 in all tasks. Discussion With no customization for the tasks and less than 5 min of end-user time to configure and launch each experiment, the average F-measure was 0.83, one point behind the mean F-measure of the 22 entrants in the competition. Strong precision scores indicate the potential of applying the approach for more specific clinical information extraction tasks. There was not one best configuration, supporting an iterative approach to model creation. Conclusion Acceptable levels of performance can be achieved using fully automated and generalizable approaches to concept-level information extraction. The described implementation and related documentation is available for download. PMID:21697292

  19. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  20. Increased levels of reduced cytochrome b and mitophagy components are required to trigger nonspecific autophagy following induced mitochondrial dysfunction.

    PubMed

    Deffieu, Maika; Bhatia-Kiššová, Ingrid; Salin, Bénédicte; Klionsky, Daniel J; Pinson, Benoît; Manon, Stéphen; Camougrand, Nadine

    2013-01-15

    Mitochondria are essential organelles producing most of the energy required for the cell. A selective autophagic process called mitophagy removes damaged mitochondria, which is critical for proper cellular homeostasis; dysfunctional mitochondria can generate excess reactive oxygen species that can further damage the organelle as well as other cellular components. Although proper cell physiology requires the maintenance of a healthy pool of mitochondria, little is known about the mechanism underlying the recognition and selection of damaged organelles. In this study, we investigated the cellular fate of mitochondria damaged by the action of respiratory inhibitors (antimycin A, myxothiazol, KCN) that act on mitochondrial respiratory complexes III and IV, but have different effects with regard to the production of reactive oxygen species and increased levels of reduced cytochromes. Antimycin A and potassium cyanide effectively induced nonspecific autophagy, but not mitophagy, in a wild-type strain of Saccharomyces cerevisiae; however, low or no autophagic activity was measured in strains deficient for genes that encode proteins involved in mitophagy, including ATG32, ATG11 and BCK1. These results provide evidence for a major role of specific mitophagy factors in the control of a general autophagic cellular response induced by mitochondrial alteration. Moreover, increased levels of reduced cytochrome b, one of the components of the respiratory chain, could be the first signal of this induction pathway. PMID:23230142

  1. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation.

    PubMed

    Darios, Emma S; Barman, Susan M; Orer, Hakan S; Morrison, Shaun F; Davis, Robert P; Seitz, Bridget M; Burnett, Robert; Watts, Stephanie W

    2015-05-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  2. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation

    PubMed Central

    Darios, Emma S.; Barman, Susan M.; Orer, Hakan S.; Morrison, Shaun F.; Davis, Robert P.; Seitz, Bridget M.; Burnett, Robert; Watts, Stephanie W.

    2015-01-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101 ± 4 to 63 ± 3 mm Hg during slow infusion of 5-HT (25 μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity was unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30 nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  3. Physical Activity Enjoyment and Self-Efficacy As Predictors of Cancer Patients' Physical Activity Level

    PubMed Central

    Ungar, Nadine; Wiskemann, Joachim; Sieverding, Monika

    2016-01-01

    Background: Physical activity (PA) can support cancer patients during medical treatment by reducing side-effects and increasing quality of life. However, PA levels mostly decline after diagnosis. Which factors can explain if patients are able to remain or even increase their PA level? Self-efficacy is an important cognitive factor that has been linked to cancer patients' PA across many studies. In contrast, affective factors such as PA enjoyment have rarely been examined. We compare the influence of self-efficacy and PA enjoyment on cancer patients' PA levels after completion of an exercise or stress-management intervention. Methods: Outpatient cancer patients [N = 72; 54% female; M = 56 years, SD = 12.34; most with breast or colon cancer (34%, 15%)] were enrolled in the MOTIVACTION study, a 4-week intervention (1 h counseling followed by weekly phone calls), with pre-test (T1), post-test (T2), and a 10-week follow-up (T3). Participants were randomized to either an exercise intervention (emphasizing self-regulatory strategies for behavior change) or to a stress management intervention (coping and relaxation techniques). Sixty-seven patients remained in the study and completed the SQUASH assessment of PA, a measure of maintenance self-efficacy (7 items, Cronbach's α = 0.88) and PA enjoyment (2 items, Cronbach's α = 0.89). Regression analyses were calculated with PA level (at T2 and T3) as dependent variable and relative weight analyses were conducted. The study was registered at clinicalTrials.gov (unique identifier:NCT01576107; URL: https://clinicaltrials.gov/ct2/show/NCT01576107?term=motivaction&rank=1). Results: Baseline self-efficacy and change in PA enjoyment significantly predicted cancer patients' PA level at T2 adjusting for baseline PA and type of intervention. Relative weight (RW) analysis revealed that PA enjoyment (baseline and change together) explained 34.3% of the dependent variable, self-efficacy (baseline and change) explained 38.4%. At follow

  4. β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease

    PubMed Central

    2015-01-01

    The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p < 0.05). β-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease (p < 0.05). Furthermore, treatment with β-glucans reduced the expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin expression in animals with diabetes and periodontal disease (p < 0.05). It was concluded that treatment with β-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease. PMID:26291983

  5. Crude caffeine reduces memory impairment and amyloid β(1-42) levels in an Alzheimer's mouse model.

    PubMed

    Chu, Yi-Fang; Chang, Wen-Han; Black, Richard M; Liu, Jia-Ren; Sompol, Pradoldej; Chen, Yumin; Wei, Huilin; Zhao, Qiuyan; Cheng, Irene H

    2012-12-01

    Alzheimer's disease (AD), a chronic neurodegenerative disorder associated with the abnormal accumulations of amyloid β (Aβ) peptide and oxidative stress in the brain, is the most common form of dementia among the elderly. Crude caffeine (CC), a major by-product of the decaffeination of coffee, has potent hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we showed that CC and pure caffeine intake had beneficial effects in a mouse model of AD. Administration of CC or pure caffeine for 2months partially prevented memory impairment in AD mice, with CC having greater effects than pure caffeine. Furthermore, consumption of CC, but not pure caffeine, reduced the Aβ(1-42) levels and the number of amyloid plaques in the hippocampus. Moreover, CC and caffeine protected primary neurons from Aβ-induced cell death and suppressed Aβ-induced caspase-3 activity. Our data indicate that CC may contain prophylactic agents against the cell death and the memory impairment in AD. PMID:22953961

  6. 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

  7. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production.

    PubMed

    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A; Zhou, Zhou; Sun, Lijie; Mathison, Angela J; Garcia-Barrio, Minerva T; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J; Rader, Daniel J; Urrutia, Raul; Chen, Y Eugene

    2015-10-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID:26368306

  8. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production

    PubMed Central

    Guo, Yanhong; Fan, Yanbo; Zhang, Jifeng; Lomberk, Gwen A.; Zhou, Zhou; Sun, Lijie; Mathison, Angela J.; Garcia-Barrio, Minerva T.; Zhang, Ji; Zeng, Lixia; Li, Lei; Pennathur, Subramaniam; Willer, Cristen J.; Rader, Daniel J.; Urrutia, Raul; Chen, Y. Eugene

    2015-01-01

    Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E–deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID:26368306

  9. Magnetospheric impulse response for many levels of geomagnetic activity

    NASA Technical Reports Server (NTRS)

    Bargatze, L. F.; Baker, D. N.; Hones, E. W., Jr.; Mcpherron, R. L.

    1985-01-01

    The temporal relationship between the solar wind and magnetospheric activity has been studied using 34 intervals of high time resolution IMP 8 solar wind data and the corresponding AL auroral activity index. The median values of the AL index for each interval were utilized to rank the intervals according to geomagnetic activity level. The linear prediction filtering technique was then applied to model magnetospheric response as measured by the AL index to the solar wind input function VB(s). The linear prediction filtering routine produces a filter of time-lagged response coefficients which estimates the most general linear relationship between the chosen input and output parameters of the magnetospheric system. It is found that the filters are composed of two response pulses speaking at time lags of 20 and 60 min. The amplitude of the 60-min pulse is the larger for moderate activity levels, while the 20-min pulse is the larger for strong activity levels. A possible interpretation is that the 20-min pulse represents magnetospheric activity driven directly by solar wind coupling and that the 60-min pulse represents magnetospheric activity driven by the release of energy previously stored in the magnetotail. If this interpretation is correct, the linear filtering results suggest that both the driven and the unloading models of magnetospheric response are important facets of a more comprehensive response model.

  10. Extraction of Children's Friendship Relation from Activity Level

    NASA Astrophysics Data System (ADS)

    Kono, Aki; Shintani, Kimio; Katsuki, Takuya; Kihara, Shin'ya; Ueda, Mari; Kaneda, Shigeo; Haga, Hirohide

    Children learn to fit into society through living in a group, and it's greatly influenced by their friend relations. Although preschool teachers need to observe them to assist in the growth of children's social progress and support the development each child's personality, only experienced teachers can watch over children while providing high-quality guidance. To resolve the problem, this paper proposes a mathematical and objective method that assists teachers with observation. It uses numerical data of activity level recorded by pedometers, and we make tree diagram called dendrogram based on hierarchical clustering with recorded activity level. Also, we calculate children's ``breadth'' and ``depth'' of friend relations by using more than one dendrogram. When we record children's activity level in a certain kindergarten for two months and evaluated the proposed method, the results usually coincide with remarks of teachers about the children.

  11. 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

  12. 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

  13. Stability of the strengthening nanoprecipitates in reduced activation ferritic steels under Fe2+ ion irradiation

    NASA Astrophysics Data System (ADS)

    Tan, L.; Katoh, Y.; Snead, L. L.

    2014-02-01

    The stability of MX-type precipitates is critical to retain mechanical properties of both reduced activation ferritic-martensitic (RAFM) and conventional FM steels at elevated temperatures. Radiation resistance of TaC, TaN, and VN nanoprecipitates irradiated up to ∼49 dpa at 500 °C using Fe2+ is investigated in this work. Transmission electron microscopy (TEM) utilized in standard and scanning mode (STEM) reveals the non-stoichiometric nature of the nanoprecipitates. Irradiation did not alter their crystalline nature. The radiation resistance of these precipitates, in an order of reduced resistance, is TaC, VN, and TaN. Particle dissolution, growth, and reprecipitation were the modes of irradiation-induced instability. Irradiation also facilitated formation of Fe2W type Laves phase limited to the VN and TaN bearing alloys. This result suggests that nitrogen level should be controlled to a minimal level in alloys to gain greater radiation resistance of the MX-type precipitates at similar temperatures as well as postpone the formation and subsequent coarsening of Laves phase.

  14. Naphthoquinone-tyrptophan reduces neurotoxic Aβ*56 levels and improves cognition in Alzheimer's disease animal model.

    PubMed

    Scherzer-Attali, R; Farfara, D; Cooper, I; Levin, A; Ben-Romano, T; Trudler, D; Vientrov, M; Shaltiel-Karyo, R; Shalev, D E; Segev-Amzaleg, N; Gazit, E; Segal, D; Frenkel, D

    2012-06-01

    An increasing body of evidence indicates a role for oligomers of the amyloid-β peptide (Aβ) in the neurotoxicity of this peptide and the pathology of Alzheimer's disease (AD). Several neurotoxic oligomeric forms of Aβ have been noted ranging from the larger Amyloid β-Derived Diffusible Ligands (ADDLs) to smaller trimers and dimers of Aβ. More recently a dodecameric form of Aβ with a 56 kDa molecular weight, denoted Aβ*56, was shown to cause memory impairment in AD model mice. Here, we present for the first time a potential therapeutic strategy for AD that targets the early stages in the formation of neurotoxic Aβ*56 oligomers using a modified quinone-Tryptophan small molecule N-(3-chloro-1,4-dihydro-1,4-dioxo-2-naphthalenyl)-L-Tryptophan (Cl-NQTrp). Using NMR spectroscopy we show that this compound binds the aromatic recognition core of Aβ and prevents the formation of oligomers. We assessed the effect of Cl-NQTrp in vivo in transgenic flies expressing Aβ(1-42) in their nervous system. When these flies were fed with Cl-NQTrp a marked alleviation of their Aβ-engendered reduced life span and defective locomotion was observed. Finally, intraperitoneal injection of Cl-NQTrp into an aggressive AD mouse model reduced the level of the Aβ*56 species in their brain and reversed their cognitive defects. Further experiments should assess whether this is a direct effect of the drug in the brain or an indirect peripheral effect. This is the first demonstration that targeted reduction of Aβ*56 results in amelioration of AD symptoms. This second generation of tryptophan-modified naphthoquinones could therefore serve as potent disease modifying therapeutic for AD. PMID:22449754

  15. Ag/ZnO heterostructures and their photocatalytic activity under visible light: effect of reducing medium.

    PubMed

    Liu, Yangsi; Wei, Shanghai; Gao, Wei

    2015-04-28

    Decoration of ZnO by Ag is a promising method to improve its photocatalytic activity and extend the photoreactivity to the visible light. In this paper, Ag/ZnO heterostructures have been synthesised by photoreduction in various reducing mediums. When the Ag/ZnO nanocomposite arrays were obtained in the air, only a small amount of Ag was reduced. Ag nanosheets and nanoparticles were formed in the water and attached on the top and side surfaces of ZnO nanorods, forming Ag/ZnO heterostructures with a nano(sheet-rod-particle) multi-level structure. In the mixture of water and ethanol, a large amount of Ag nanoclusters was produced and embedded in the ZnO nanorod arrays. The influence of reducing mediums on the microstructure, morphology, quantity and dispersion of Ag nanostructures was investigated; and the effect of Ag component on the optical properties and visible light driven photocatalytic behaviour of the Ag/ZnO heterostructures was discussed. PMID:25621832

  16. Shear stress reduces protease activated receptor-1 expression in human endothelial cells

    NASA Technical Reports Server (NTRS)

    Nguyen, K. T.; Eskin, S. G.; Patterson, C.; Runge, M. S.; McIntire, L. V.

    2001-01-01

    Shear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of vascular injury, which suggests an important role for PAR-1 in vascular diseases. However, the effect of shear stress on PAR-1 expression has not been previously studied. This work investigates effects of shear stress on PAR-1 gene expression in both human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (HMECs). Cells were exposed to different shear stresses using a parallel plate flow system. Northern blot and flow cytometry analysis showed that shear stress down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was due to a decrease of transcription rate, not increased mRNA degradation. Postshear stress release of endothelin-1 in response to thrombin was reduced in HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied during shear stress indicated mediation of the shear-decreased PAR-1 expression by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene expression in HMECs and HUVECs through a mechanism dependent in part on protein kinases, leading to altered endothelial cell functional responses to thrombin.

  17. ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity

    PubMed Central

    Porritt, Michelle J; Chen, Michelle; Rewell, Sarah S J; Dean, Rachael G; Burrell, Louise M; Howells, David W

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR. PMID:20407464

  18. Reduced posterior parietal cortex activation after training on a visual search task.

    PubMed

    Bueichekú, Elisenda; Miró-Padilla, Anna; Palomar-García, María-Ángeles; Ventura-Campos, Noelia; Parcet, María-Antonia; Barrós-Loscertales, Alfonso; Ávila, César

    2016-07-15

    Gaining experience on a cognitive task improves behavioral performance and is thought to enhance brain efficiency. Despite the body of literature already published on the effects of training on brain activation, less research has been carried out on visual search attention processes under well controlled conditions. Thirty-six healthy adults divided into trained and control groups completed a pre-post letter-based visual search task fMRI study in one day. Twelve letters were used as targets and ten as distractors. The trained group completed a training session (840 trials) with half the targets between scans. The effects of training were studied at the behavioral and brain levels by controlling for repetition effects using both between-subjects (trained vs. control groups) and within-subject (trained vs. untrained targets) controls. The trained participants reduced their response speed by 31% as a result of training, maintaining their accuracy scores, whereas the control group hardly changed. Neural results revealed that brain changes associated with visual search training were circumscribed to reduced activation in the posterior parietal cortex (PPC) when controlling for group, and they included inferior occipital areas when controlling for targets. The observed behavioral and brain changes are discussed in relation to automatic behavior development. The observed training-related decreases could be associated with increased neural efficiency in specific key regions for task performance. PMID:27132048

  19. Activity level and risk of overweight in male health professionals.

    PubMed Central

    Ching, P L; Willett, W C; Rimm, E B; Colditz, G A; Gortmaker, S L; Stampfer, M J

    1996-01-01

    OBJECTIVES. This study undertook to examine relationships between nonsedentary activity level, time spent watching television (TV)/videocassette recorder (VCR), and risk of overweight among men. METHODS. Men participating in the Health Professionals Follow-Up Study were mailed surveys. Cross-sectional analyses examined the prevalence and odds of being overweight, prospective analyses determined cumulative incidence rates and relative risks of becoming overweight over 2 years of follow-up. RESULTS. Cross-sectionally, odds of being overweight were 50% (95% confidence interval [CI] = 45%; 55%) lower for men in the highest quintile of nonsedentary activity level when compared with men in the lowest quintile. Among men watching 41 or more hours of TV/VCR per week, the odds of being overweight were 406 (95% CI = 2.67, 6.17) times greater than those for men watching no more than 1 hour per week. Prospectively, higher levels is of nonsedentary activity and lower levels of TV/VCR viewing were independently associated with lower relative risks for becoming overweight between survey years. CONCLUSIONS. Both a lack of nonsedentary activity and time spent watching TV/VCR contribute to the development of overweight in men. Sedentary and nonsedentary activities represent separate domains, each with independent risks for overweight. PMID:8561237

  20. Arginine vasotocin reduces levels of cooperative behaviour in a cleaner fish.

    PubMed

    Cardoso, Sónia C; Paitio, José R; Oliveira, Rui F; Bshary, Redouan; Soares, Marta C

    2015-02-01

    Cooperation between unrelated individuals usually involves investments that often mean a decrease in immediate payoffs, but ensure future benefits. Here we investigated the potential role of the neuropeptides Arginine-vasotocin (AVT) and Isotocin (IT) as proximate agents affecting individuals' cooperative levels in the Indo-pacific bluestreak cleaner wrasse Labroides dimidiatus. Their 'client' reef fish partners only benefit from interacting if cleaners eat ectoparasites and refrain from gleaning preferred client mucus. Thus, cleaners must control their impulse to eat according to their preference, and eat less preferred items to maintain ongoing interactions and avoid clients' leaving or punishing. We found that solely the experimental transient higher dosage of AVT led to a decrease of cleaners' willingness to feed against their preference, while IT and AVT antagonists had no significant effects. The sole effect of AVT on cleaner's performance may imply a link between AVT's influence and a potential activation of a stress response. Our results confirm the importance of the AVT/AVP system as an agent affecting levels of cooperation, offering a potential mechanistic pathway for the reported flexible service quality that cleaners provide their clients. PMID:25449412

  1. Ethanol exposure affects gene expression in the embryonic organizer and reduces retinoic acid levels.

    PubMed

    Yelin, Ronit; Schyr, Racheli Ben-Haroush; Kot, Hadas; Zins, Sharon; Frumkin, Ayala; Pillemer, Graciela; Fainsod, Abraham

    2005-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is a set of developmental malformations caused by alcohol consumption during pregnancy. Fetal Alcohol Syndrome (FAS), the strongest manifestation of FASD, results in short stature, microcephally and facial dysmorphogenesis including microphthalmia. Using Xenopus embryos as a model developmental system, we show that ethanol exposure recapitulates many aspects of FAS, including a shortened rostro-caudal axis, microcephally and microphthalmia. Temporal analysis revealed that Xenopus embryos are most sensitive to ethanol exposure between late blastula and early/mid gastrula stages. This window of sensitivity overlaps with the formation and early function of the embryonic organizer, Spemann's organizer. Molecular analysis revealed that ethanol exposure of embryos induces changes in the domains and levels of organizer-specific gene expression, identifying Spemann's organizer as an early target of ethanol. Ethanol also induces a defect in convergent extension movements that delays gastrulation movements and may affect the overall length. We show that mechanistically, ethanol is antagonistic to retinol (Vitamin A) and retinal conversion to retinoic acid, and that the organizer is active in retinoic acid signaling during early gastrulation. The model suggests that FASD is induced in part by an ethanol-dependent reduction in retinoic acid levels that are necessary for the normal function of Spemann's organizer. PMID:15708568

  2. 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

  3. Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

    PubMed Central

    Wöhr, Markus; Roullet, Florence I.; Hung, Albert Y.; Sheng, Morgan; Crawley, Jacqueline N.

    2011-01-01

    Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism. PMID:21695253

  4. (Reduce uncertainty in projection of future sea-level change due to ice wastage)

    SciTech Connect

    Meier, M.F.

    1991-01-01

    Three basic goals were stated in the original proposal. These were: (1) develop an understanding of the heat and mass flow into subfreezing snow and firn, in order to model the evolution of the temperature distribution and the infiltration rates through the firn; (2) relate changes in climate, as given by general circulation model predictions, to changes in the surface mass and energy balances of glaciers; and (3) use the above results to analyze the effects of changed surface mass and energy balances on the flow of meltwater through snow and firn, and on the runoff from these glaciers, in a CO{sub 2}-affected climate. This final report summarizes our progress toward these goals. The primary product of this research program has been the communication of this progress in the form of publications in the scientific literature and presentations at scientific meetings. Our research activities in the past three years have provided a new basis for modeling of multiphase flow in subfreezing snow, new field data on the structural properties of arctic firn pertinent to hydrological modeling, and estimates of sea level change in response to changing patterns of runoff from the Greenland Ice Sheet. We conclude that forecasts of future sea level changes from all glacier runoff sources may be in error by amounts on the order of +8 cm over the next 150 years, due to the lag in generating runoff to the sea. Our specific research products include two distributed-parameter models of water flow through snow with melting and freezing, a theoretical model of wetting-front advance into subfreezing snow for inclusion in a future model, and a simple large-scale model of the response of Greenland runoff in a changing climate which provides estimates of the effect of melt water refreezing phenomena on sea level changes in response to a range of possible future climates.

  5. Reduced Levels of Proteasome Products in a Mouse Striatal Cell Model of Huntington’s Disease

    PubMed Central

    Dasgupta, Sayani; Fishman, Michael A.; Mahallati, Hana; Castro, Leandro M.; Tashima, Alexandre K.; Ferro, Emer S.; Fricker, Lloyd D.

    2015-01-01

    Huntington’s disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7) or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111) or homozygous (STHdhQ111/Q111). Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts. PMID:26691307

  6. 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

  7. Auxotrophic Mutations Reduce Tolerance of Saccharomyces cerevisiae to Very High Levels of Ethanol Stress

    PubMed Central

    Swinnen, Steve; Goovaerts, Annelies; Schaerlaekens, Kristien; Dumortier, Françoise; Verdyck, Pieter; Souvereyns, Kris; Van Zeebroeck, Griet; Foulquié-Moreno, María R.

    2015-01-01

    Very high ethanol tolerance is a distinctive trait of the yeast Saccharomyces cerevisiae with notable ecological and industrial importance. Although many genes have been shown to be required for moderate ethanol tolerance (i.e., 6 to 12%) in laboratory strains, little is known of the much higher ethanol tolerance (i.e., 16 to 20%) in natural and industrial strains. We have analyzed the genetic basis of very high ethanol tolerance in a Brazilian bioethanol production strain by genetic mapping with laboratory strains containing artificially inserted oligonucleotide markers. The first locus contained the ura3Δ0 mutation of the laboratory strain as the causative mutation. Analysis of other auxotrophies also revealed significant linkage for LYS2, LEU2, HIS3, and MET15. Tolerance to only very high ethanol concentrations was reduced by auxotrophies, while the effect was reversed at lower concentrations. Evaluation of other stress conditions showed that the link with auxotrophy is dependent on the type of stress and the type of auxotrophy. When the concentration of the auxotrophic nutrient is close to that limiting growth, more stress factors can inhibit growth of an auxotrophic strain. We show that very high ethanol concentrations inhibit the uptake of leucine more than that of uracil, but the 500-fold-lower uracil uptake activity may explain the strong linkage between uracil auxotrophy and ethanol sensitivity compared to leucine auxotrophy. Since very high concentrations of ethanol inhibit the uptake of auxotrophic nutrients, the active uptake of scarce nutrients may be a major limiting factor for growth under conditions of ethanol stress. PMID:26116212

  8. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  9. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

    PubMed Central

    Austin, Adelaide; Jiga-Boy, Gabriela M.; Rea, Sara; Newstead, Simon A.; Roderick, Sian; Davis, Nick J.; Clement, R. Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  10. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors.

    PubMed

    Austin, Adelaide; Jiga-Boy, Gabriela M; Rea, Sara; Newstead, Simon A; Roderick, Sian; Davis, Nick J; Clement, R Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  11. Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels

    PubMed Central

    Alcaraz, M; Armero, D; Martínez-Beneyto, Y; Castillo, J; Benavente-García, O; Fernandez, H; Alcaraz-Saura, M; Canteras, M

    2011-01-01

    Objectives The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible. Methods Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 μM 5 min before exposure to irradiation by 2 Gy of X-rays. Results The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity. Conclusion Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected. PMID:21697157

  12. NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat.

    PubMed

    Zhong, Chunlong; Zhao, Xueren; Van, Ken C; Bzdega, Tomasz; Smyth, Aoife; Zhou, Jia; Kozikowski, Alan P; Jiang, Jiyao; O'Connor, William T; Berman, Robert F; Neale, Joseph H; Lyeth, Bruce G

    2006-05-01

    Traumatic brain injury (TBI) produces a rapid and excessive elevation in extracellular glutamate that induces excitotoxic brain cell death. The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) is reported to suppress neurotransmitter release through selective activation of presynaptic group II metabotropic glutamate receptors. Therefore, strategies to elevate levels of NAAG following brain injury could reduce excessive glutamate release associated with TBI. We hypothesized that the NAAG peptidase inhibitor, ZJ-43 would elevate extracellular NAAG levels and reduce extracellular levels of amino acid neurotransmitters following TBI by a group II metabotropic glutamate receptor (mGluR)-mediated mechanism. Dialysate levels of NAAG, glutamate, aspartate and GABA from the dorsal hippocampus were elevated after TBI as measured by in vivo microdialysis. Dialysate levels of NAAG were higher and remained elevated in the ZJ-43 treated group (50 mg/kg, i.p.) compared with control. ZJ-43 treatment also reduced the rise of dialysate glutamate, aspartate, and GABA levels. Co-administration of the group II mGluR antagonist, LY341495 (1 mg/kg, i.p.) partially blocked the effects of ZJ-43 on dialysate glutamate and GABA, suggesting that NAAG effects are mediated through mGluR activation. The results are consistent with the hypothesis that inhibition of NAAG peptidase may reduce excitotoxic events associated with TBI. PMID:16606367

  13. Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass*

    PubMed Central

    Kular, Jasreen; Tickner, Jennifer C.; Pavlos, Nathan J.; Viola, Helena M.; Abel, Tamara; Lim, Bay Sie; Yang, Xiaohong; Chen, Honghui; Cook, Robert; Hool, Livia C.; Zheng, Ming Hao; Xu, Jiake

    2015-01-01

    The maintenance of bone homeostasis requires tight coupling between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the precise molecular mechanism(s) underlying the differentiation and activities of these specialized cells are still largely unknown. Here, we identify choline kinase β (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase β mutant mice (flp/flp) exhibit a systemic low bone mass phenotype. Consistently, osteoclast numbers and activity are elevated in flp/flp mice. Interestingly, osteoclasts derived from flp/flp mice exhibit reduced sensitivity to excessive levels of extracellular calcium, which could account for the increased bone resorption. Conversely, supplementation of cytidine 5′-diphosphocholine in vivo and in vitro, a regimen that bypasses CHKB deficiency, restores osteoclast numbers to physiological levels. Finally, we demonstrate that, in addition to modulating osteoclast formation and function, loss of CHKB corresponds with a reduction in bone formation by osteoblasts. Taken together, these data posit CHKB as a new modulator of bone homeostasis. PMID:25451916

  14. Reduced polarization decay due to carrier in-scattering in a semiconductor active medium

    SciTech Connect

    Hughes, S.; Knorr, A.; Koch, S.W.; Chow, W.W.

    1996-07-01

    The in-scattering processes, which reduce the decay of the active medium polarization, should be included in a consistent treatment of semiconductor laser gain. The in-scattering processes affect the laser gain by decreasing the influence of the high k-states, which contribute absorption to the spectrum. A theory, based on the semiconductor-Bloch equations with the effects of carrier-carrier scattering treated at the level of the quantum kinetic equations in the Markov limit, predicts gain spectra that do not exhibit absorption below the renormalized band gap, in agreement with experiment. When compared to gain calculations where the in-scattering contribution is neglected, the theory predicts markedly different properties for intrinsic laser parameters, such as peak gain, gain bandwidth, differential gain and carrier density at transparency, especially at low carrier densities.

  15. Hydrogen Embrittlement Susceptibility of Conventional and Reduced Activation 9Cr-Steels

    SciTech Connect

    Maday, Marie-Francoise

    2005-05-15

    Hydrogen embrittlement behaviour of the reduced activation ferritic/martensitic steels, Eurofer'97 and VS3104, has been compared to that of the conventional alloy T91, by means of constant extension rate tests run under dynamic electrochemical charging. Charged versus uncharged reduction of specimen area ratios at rupture were taken as the most suitable ductility indexes for material discrimination in terms of hydrogen damage resistance. Fractographic analysis indicated that hydrogen content as low as 1.6 wppm caused rupture of al investigated steels, but to different degree, by promoting grain boundary decohesion. Higher hydrogen levels stimulated failure by the combined effect of bond strength weakening and stress intensification from dislocation blocking at interfaces. The better performances of T91 as well as the variability of Eurofer tensile responses were ascribed to the different chemistry and density of key microstructural factors, already suspected from metallurgical examination and further supported by hydrogen thermal extraction results.

  16. The use of an air bubble curtain to reduce the received sound levels for harbor porpoises (Phocoena phocoena).

    PubMed

    Lucke, Klaus; Lepper, Paul A; Blanchet, Marie-Anne; Siebert, Ursula

    2011-11-01

    In December 2005 construction work was started to replace a harbor wall in Kerteminde harbor, Denmark. A total of 175 wooden piles were piled into the ground at the waters edge over a period of 3 months. During the same period three harbor porpoises were housed in a marine mammal facility on the opposite side of the harbor. All animals showed strong avoidance reactions after the start of the piling activities. As a measure to reduce the sound exposure for the animals an air bubble curtain was constructed and operated in a direct path between the piling site and the opening of the animals' semi-natural pool. The sound attenuation effect achieved with this system was determined by quantitative comparison of pile driving impulses simultaneously measured in front of and behind the active air bubble curtain. Mean levels of sound attenuation over a sequence of 95 consecutive pile strikes were 14 dB (standard deviation (s.d.) 3.4 dB) for peak to peak values and 13 dB (s.d. 2.5 dB) for SEL values. As soon as the air bubble curtain was installed and operated, no further avoidance reactions of the animals to the piling activities were apparent. PMID:22088014

  17. Laquinimod decreases Bax expression and reduces caspase-6 activation in neurons.

    PubMed

    Ehrnhoefer, Dagmar E; Caron, Nicholas S; Deng, Yu; Qiu, Xiaofan; Tsang, Michelle; Hayden, Michael R

    2016-09-01

    Laquinimod is an immunomodulatory compound that has shown neuroprotective benefits in clinical trials for multiple sclerosis. Laquinimod ameliorates both white and gray matter damage in human patients, and prevents axonal degeneration in animal models of multiple sclerosis. Axonal damage and white matter loss are a common feature shared between different neurodegenerative diseases. Caspase-6 activation plays an important role in axonal degeneration on the molecular level. Increased activity of caspase-6 has been demonstrated in brain tissue from presymptomatic Huntington disease mutation carriers, and it is an early marker of axonal dysfunction. Since laquinimod is currently undergoing a clinical trial in Huntington disease (LEGATO-HD, clinicaltrials.gov ID: NCT02215616), we set out to evaluate its impact on neuronal caspase-6 activation. We find that laquinimod ameliorates DNA-damage induced activation of caspase-6 in primary neuronal cultures. This is an indirect effect that is not mediated by direct inhibition of the enzyme. The investigation of potential caspase-6 activating mechanisms revealed that laquinimod reduces the expression of Bax, a pro-apoptotic molecule that causes mitochondrial cytochrome c release and caspase activation. Bax expression is furthermore increased in striatal tissues from the YAC128 mouse model of HD in an age-dependent manner. Our results demonstrate that laquinimod can directly downregulate neuronal apoptosis pathways relevant for axonal degeneration in addition to its known effects on astrocytes and microglia in the CNS. It targets a pathway that is relevant for the pathogenesis of HD, supporting the hypothesis that laquinimod may provide clinical benefit. PMID:27296315

  18. Reconstituted high-density lipoproteins acutely reduce soluble brain Aβ levels in symptomatic APP/PS1 mice.

    PubMed

    Robert, Jérôme; Stukas, Sophie; Button, Emily; Cheng, Wai Hang; Lee, Michael; Fan, Jianjia; Wilkinson, Anna; Kulic, Iva; Wright, Samuel D; Wellington, Cheryl L

    2016-05-01

    Many lines of evidence suggest a protective role for high-density lipoprotein (HDL) and its major apolipoprotein (apo)A-I in Alzheimer's Disease (AD). HDL/apoA-I particles are produced by the liver and intestine and, in addition to removing excess cholesterol from the body, are increasingly recognized to have vasoprotective functions. Here we tested the ability of reconstituted HDL (rHDL) consisting of human apoA-I reconstituted with soy phosphatidylcholine for its ability to lower amyloid beta (Aβ) levels in symptomatic APP/PS1 mice, a well-characterized preclinical model of amyloidosis. Animals were treated intravenously either with four weekly doses (chronic study) or a single dose of 60mg/kg of rHDL (acute study). The major finding of our acute study is that soluble brain Aβ40 and Aβ42 levels were significantly reduced within 24h of a single dose of rHDL. By contrast, no changes were observed in our chronic study with respect to soluble or deposited Aβ levels in animals assessed 7days after the final weekly dose of rHDL, suggesting that beneficial effects diminish as rHDL is cleared from the body. Further, rHDL-treated animals showed no change in amyloid burden, cerebrospinal fluid (CSF) Aβ levels, neuroinflammation, or endothelial activation in the chronic study, suggesting that the pathology-modifying effects of rHDL may indeed be acute and may be specific to the soluble Aβ pool. That systemic administration of rHDL can acutely modify brain Aβ levels provides support for further investigation of the therapeutic potential of apoA-I-based agents for AD. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26454209

  19. 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

  20. 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

  1. Online Activity Levels Are Related to Caffeine Dependency.

    PubMed

    Phillips, James G; Landhuis, C Erik; Shepherd, Daniel; Ogeil, Rowan P

    2016-05-01

    Online activity could serve in the future as behavioral markers of emotional states for computer systems (i.e., affective computing). Hence, this study considered relationships between self-reported stimulant use and online study patterns. Sixty-two undergraduate psychology students estimated their daily caffeine use, and this was related to study patterns as tracked by their use of a Learning Management System (Blackboard). Caffeine dependency was associated with less time spent online, lower rates of file access, and fewer online activities completed. Reduced breadth or depth of processing during work/study could be used as a behavioral marker of stimulant use. PMID:27096737

  2. Cascading Activation across Levels of Representation in Children's Lexical Processing

    ERIC Educational Resources Information Center

    Huang, Yi Ting; Snedeker, Jesse

    2011-01-01

    Recent work in adult psycholinguistics has demonstrated that activation of semantic representations begins long before phonological processing is complete. This incremental propagation of information across multiple levels of analysis is a hallmark of adult language processing but how does this ability develop? In two experiments, we elicit…

  3. Education Finance Legislative Activity and Trends at the State Level.

    ERIC Educational Resources Information Center

    Crampton, Faith E.

    1999-01-01

    Reviews 1997 school finance legislation, comparing legislative activity levels from 1994 to 1997. In 1997, 32 states passed legislation pertaining to capital-outlay funding, tax bases, and taxation for education funding. Half passed legislation for state aid, technology, special-purpose education, budgeting/fiscal management, and school personnel…

  4. 34 CFR 300.704 - State-level activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false State-level activities. 300.704 Section 300.704 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH DISABILITIES Authorization,...

  5. 34 CFR 300.814 - Other State-level activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Other State-level activities. 300.814 Section 300.814 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION...

  6. Pedometer-Assessed Physical Activity Levels of Rural Appalachian Youth

    ERIC Educational Resources Information Center

    Oh, Hyun-Ju; Rana, Sharon

    2014-01-01

    The purposes of this investigation were to examine whether pedometer-assessed physical activity (PA) in Appalachian Ohio students differed by body mass index (BMI), school level (middle school vs. high school), and gender during school days and nonschool days and whether students met the recommended PA guidelines. Participants (N = 149) were…

  7. Cardiovascular effects of variations in habitual levels of physical activity

    NASA Technical Reports Server (NTRS)

    Blomqvist, C. G.; Mitchell, J. H.

    1975-01-01

    Mechanisms involved in human cardiovascular adaption to stress, particularly adaption to different levels of physical activity are determined along with quantitative noninvasive methods for evaluation of cardiovascular function during stess in normal subjects and in individuals with latent or manifest cardiovascular disease. Results are summarized.

  8. N-acetyltransferase 2 activity and folate levels

    PubMed Central

    Cao, Wen; Strnatka, Diana; McQueen, Charlene A.; Hunter, Robert J.; Erickson, Robert P.

    2010-01-01

    Aims To determine whether increased N-acetyltransferase (NAT) activity might have a toxic effect during development and an influence on folate levels since previous work has shown that only low levels of exogenous NAT can be achieved in constitutionally transgenic mice (Cao, et al, 2005) Main Methods A human NAT1 tet-inducible construct was used that would not be expressed until the inducer was delivered. Human NAT1 cDNA was cloned into pTRE2 and injected into mouse oocytes. Two transgenic lines were crossed to mouse line TgN(rtTahCMV)4Uh containing the CMV promoted “teton.”Measurements of red blood cell folate levels in inbred strains of mice were performed. Key findings Only low levels of human NAT1 could be achieved in kidney (highly responsive in other studies) whether the inducer, doxycycline, was given by gavage or in drinking water.An inverse correlation of folate levels with Nat2 enzyme activity was found. Significance Since increasing NAT1 activity decrease folate in at least one tissue, the detrimental effect of expression of human NAT1 in combination with endogenous mouse Nat2 may be a consequence of increased catabolism of folate. PMID:19932120

  9. Effect of apple pomace fiber and pork fat levels on quality characteristics of uncured, reduced-fat chicken sausages.

    PubMed

    Choi, Yun-Sang; Kim, Young-Boong; Hwang, Ko-Eun; Song, Dong-Heon; Ham, Youn-Kyung; Kim, Hyun-Wook; Sung, Jung-Min; Kim, Cheon-Jei

    2016-06-01

    The effects of reducing pork fat level from 30 to 25 and 20% by partially substituting pork fat with 1 and 2% apple pomace fiber were investigated based on the evaluation of physicochemical properties and textural properties of uncured, reduced-fat chicken sausages. Increased fat level resulted in decreased moisture content, cooking loss, total expressible fluid separation, fat separation, and yellowness of uncured, reduced-fat chicken sausages, whereas, an increase in fat content, caloric energy, pH, lightness, redness, hardness, cohesiveness, gumminess, and chewiness was observed. The results showed that uncured, reduced-fat chicken sausage samples with increased apple pomace fiber level had lower cooking loss, total expressible fluid separation, fat separation, pH, and redness. The results from this study show that inclusion of apple pomace fiber in the formulation will successfully reduce fat content in emulsion sausages, while improving quality characteristics relative to regular-fat (30%) control. PMID:27030694

  10. Can nursing students' confidence levels increase with repeated simulation activities?

    PubMed

    Cummings, Cynthia L; Connelly, Linda K

    2016-01-01

    In 2014, nursing faculty conducted a study with undergraduate nursing students on their satisfaction, confidence, and educational practice levels, as it related to simulation activities throughout the curriculum. The study was a voluntary survey conducted on junior and senior year nursing students. It consisted of 30 items based on the Student Satisfaction and Self-Confidence in Learning and the Educational Practices Questionnaire (Jeffries, 2012). Mean averages were obtained for each of the 30 items from both groups and were compared using T scores for unpaired means. The results showed that 8 of the items had a 95% confidence level and when combined the items were significant for p <.001. The items identified were those related to self-confidence and active learning. Based on these findings, it can be assumed that repeated simulation experiences can lead to an increase in student confidence and active learning. PMID:26599594

  11. Reduced alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes as a modulator of fasting and postprandial triglyceride levels in men.

    PubMed

    Imbeault, P; Couillard, C; Tremblay, A; Després, J P; Mauriège, P

    2000-09-01

    This study examined the postprandial lipemia of two groups of men displaying similar age, body weight, and regional fat distribution, but characterized by either low (n = 11) or high (n = 15) alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes. In addition to fat cell lipolysis, adipose tissue lipoprotein lipase (AT-LPL) as well as postheparin plasma LPL activities were measured in the fasting state. Fasting AT-LPL and PH-LPL activities were similar in both groups. Maximal adipose cell lipolysis induced by isoproterenol (beta-adrenergic agonist) as well as the beta-adrenergic sensitivity did not differ between both groups of men. The selective alpha(2)-adrenergic agonist UK-14304 promoted a similar antilipolytic response in subcutaneous abdominal adipocytes from both groups. However, the alpha(2)-adrenergic sensitivity, defined as the dose of UK-14304 that produced half-maximal inhibition of lipolysis (IC(50)), was significantly different between groups (P < 0.0001). Men with low versus high subcutaneous abdominal fat cell alpha(2)-adrenergic sensitivity showed higher fasting TG levels. In the whole group, a positive relationship was observed between log-transformed IC(50) UK-14304 values of subcutaneous adipocytes and fasting TG levels (r = 0.39, P < 0.05), suggesting that a low abdominal adipose cell alpha(2)-adrenergic sensitivity is associated with high TG levels. After the consumption of a high-fat meal, subjects with low subcutaneous abdominal adipose cell alpha(2)-adrenergic sensitivity showed higher TG levels in total, medium, and small triglyceride-rich lipoprotein (TRL) fractions at 0- to 6-h time points than men with high adipocyte alpha(2)-adrenergic sensitivity (P values ranging from 0.01 to 0.05). Stepwise regression analysis showed that the fasting TG concentration was the only variable retained as a significant predictor of the area under the curve of TG levels in total TRL fractions (73% of variance) among independent variables

  12. Displacement Behaviour Is Associated with Reduced Stress Levels among Men but Not Women

    PubMed Central

    Mohiyeddini, Changiz; Bauer, Stephanie; Semple, Stuart

    2013-01-01

    Sex differences in the ability to cope with stress may contribute to the higher prevalence of stress-related disorders among women compared to men. We recently provided evidence that displacement behaviour - activities such as scratching and face touching - represents an important strategy for coping with stressful situations: in a healthy population of men, displacement behaviour during a social stress test attenuated the relationship between anxiety experienced prior to this test, and the subsequent self-reported experience of stress. Here, we extend this work to look at physiological and cognitive (in addition to self-reported) measures of stress, and study both men and women in order to investigate whether sex moderates the link between displacement behaviour and the response to stress. In a healthy study population, we quantified displacement behaviour, heart rate and cognitive performance during the Trier Social Stress Test, and used self-report questionnaires to assess the experience of stress afterwards. Men engaged in displacement behaviour about twice as often as women, and subsequently reported lower levels of stress. Bivariate correlations revealed that for men, higher rates of displacement behaviour were associated with decreased self-reported stress, fewer mistakes in the cognitive task and a trend towards lower heart rate; no relationships between displacement behaviour and stress measures were found for women. Moreover, moderation analyses revealed that high rates of displacement behaviour were associated with lower stress levels in men but not in women, and that high displacement behaviour rates were associated with poorer cognitive performance in women, but not men. These results point to an important sex difference in coping strategies, and highlight new avenues for research into sex biases in stress-related disorders. PMID:23457555

  13. Effects of Curricular Activity on Students' Situational Motivation and Physical Activity Levels

    ERIC Educational Resources Information Center

    Gao, Zan; Hannon, James C.; Newton, Maria; Huang, Chaoqun

    2011-01-01

    The purpose of this study was to examine (a) the effects of three curricular activities on students' situational motivation (intrinsic motivation [IM], identified regulation [IR], external regulation, and amotivation [AM]) and physical activity (PA) levels, and (b) the predictive strength of situational motivation to PA levels. Four hundred twelve…

  14. Physical Activity Levels in American-Indian Adults

    PubMed Central

    Storti, Kristi L.; Arena, Vincent C.; Barmada, M. Michael; Bunker, Clareann H.; Hanson, Robert L.; Laston, Sandra L.; Yeh, Jeun-Liang; Zmuda, Joseph M.; Howard, Barbara V.; Kriska, Andrea M.

    2009-01-01

    Background A limited body of evidence, mostly based on self-report, is available regarding physical activity levels among American-Indian adults. Purpose This study aims to examine physical activity levels objectively by pedometer among a large cohort of American Indian adult participants in the Strong Heart Family Study. Methods Physical activity levels in 2604 American-Indian adults, aged 18–91 years, from 13 American-Indian communities were assessed using an Accusplit AE120 pedometer over a period of 7 days during 2001–2003. Anthropometric measurements were also assessed. All data analyses were conducted in 2008. Age-adjusted Pearson correlations were used to examine the relationship between average steps per day and age and anthropometric variables. Subjects were placed in age and BMI categories (according to NHLBI cutpoints) to examine trends in PA with increasing age and BMI. Results Daily pedometer steps ranged from 1001 to 38,755. Mean step counts by age group for men were: 5384 (18–29 years), 5120 (30–39 years), 5040 (40–49 years), 4561(50–59 years),4321 (60–69 years), and 3768 (≥70 years) and for women: 5038 (18–29 years), 5112 (30– 39 years), 5054 (40–49 years), 4582 (50–59 years), 3653 (60–69 years), and 3770 (>70 years). A significant linear trend in physical activity was noted with increasing age (P= 0.002 for men, P<0.0001 for women) and with increasing BMI (P = 0.05 for men, P = 0.04 for women). Conclusions Objectively measured data suggest that inactivity is a problem among American Indian adults and that a majority of American Indian adults in the SHFS may not be meeting the minimum physical activity public health recommendations. Efforts to increase physical activity levels in this population are warranted. PMID:19944912

  15. 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

  16. 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

  17. Spinal cord stimulation reduces mechanical hyperalgesia and glial cell activation in animals with neuropathic pain

    PubMed Central

    Sato, Karina L.; Johanek, Lisa M.; Sanada, Luciana S.; Sluka, Kathleen A.

    2015-01-01

    Spinal cord stimulation (SCS) is used to manage chronic intractable neuropathic pain. We examined parameters of SCS in rats with spared nerve injury by modulating frequency (4Hz vs. 60Hz), duration (30m vs. 6h), or intensity (50%, 75%, or 90% MT). To elucidate potential mechanisms modulated by SCS, we examined immunoreactivity glial markers in the spinal cord after SCS). An epidural SCS lead was implanted in the upper lumbar spinal cord. Animals were tested for mechanical withdrawal threshold (MWT) of the paw before and 2 weeks after SNI, before and after SCS daily for 4 days, and for 9 days after SCS. Seperate groups of animals were tested for glial immunoreactivity after 4 days of 6h SCS. All rats showed a decrease in MWT 2 weeks after nerve injury and an increase in glial activation. For frequency, 4Hz or 60Hz SCS reversed the MWT when compared to sham SCS. For duration, 6h of SCS showed a greater reduction in MWT when compared to 30 min. For intensity, 90% MT was greater than 75% MT and both were greater than 50% MT or sham SCS. SCS decreased glial activation (GFAP, MCP-1 and OX-42) in the spinal cord dorsal horn when compared to sham. In conclusion, 4Hz and 60Hz SCS for a 6h at 90% MT were the most effective parameters for reducing hyperalgesia, suggesting parameters of stimulation are important for effectiveness of SCS. SCS reduced glial activation at the level of the spinal cord suggesting reduction in central excitability. PMID:24361846

  18. Reduced gene expression levels after chronic exposure to high concentrations of air pollutants.

    PubMed

    Rossner, Pavel; Tulupova, Elena; Rossnerova, Andrea; Libalova, Helena; Honkova, Katerina; Gmuender, Hans; Pastorkova, Anna; Svecova, Vlasta; Topinka, Jan; Sram, Radim J

    2015-10-01

    We analyzed the ability of particulate matter (PM) and chemicals adsorbed onto it to induce diverse gene expression profiles in subjects living in two regions of the Czech Republic differing in levels and sources of the air pollution. A total of 312 samples from polluted Ostrava region and 154 control samples from Prague were collected in winter 2009, summer 2009 and winter 2010. The highest concentrations of air pollutants were detected in winter 2010 when the subjects were exposed to: PM of aerodynamic diameter <2.5μm (PM2.5) (70 vs. 44.9μg/m(3)); benzo[a]pyrene (9.02 vs. 2.56ng/m(3)) and benzene (10.2 vs. 5.5μg/m(3)) in Ostrava and Prague, respectively. Global gene expression analysis of total RNA extracted from leukocytes was performed using Illumina Expression BeadChips microarrays. The expression of selected genes was verified by quantitative real-time PCR (qRT-PCR). Gene expression profiles differed by locations and seasons. Despite lower concentrations of air pollutants a higher number of differentially expressed genes and affected KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was found in subjects from Prague. In both locations immune response pathways were affected, in Prague also neurodegenerative diseases-related pathways. Over-representation of the latter pathways was associated with the exposure to PM2.5. The qRT-PCR analysis showed a significant decrease in expression of APEX, ATM, FAS, GSTM1, IL1B and RAD21 in subjects from Ostrava, in a comparison of winter 2010 and summer 2009. In Prague, an increase in gene expression was observed for GADD45A and PTGS2. In conclusion, high concentrations of pollutants in Ostrava were not associated with higher number of differentially expressed genes, affected KEGG pathways and expression levels of selected genes. This observation suggests that chronic exposure to air pollution may result in reduced gene expression response with possible negative health consequences. PMID:26298100

  19. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    USGS Publications Warehouse

    Ransom, Jason I.; Powers, Jenny G.; Hobbs, N. Thompson; Baker, Dan L.

    2014-01-01

    1. Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. 2. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. 3. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. 4. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. 5. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife

  20. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    PubMed Central

    Ransom, Jason I; Powers, Jenny G; Thompson Hobbs, N; Baker, Dan L

    2014-01-01

    Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife contraception, managers

  1. Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication

    PubMed Central

    Seok, Su-Jin; Kim, Su-Ji; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young

    2011-01-01

    To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication. PMID:21468253

  2. 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

  3. Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

    PubMed Central

    Yüksel, Meral; Okur, Hacer Kuzu; Pelin, Zerrin; Öğünç, Ayliz Velioğlu; Öztürk, Levent

    2014-01-01

    OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels. PMID:24714832

  4. Enhanced fluorescence cyanide detection at physiologically lethal levels: reduced ICT-based signal transduction.

    PubMed

    Badugu, Ramachandram; Lakowicz, Joseph R; Geddes, Chris D

    2005-03-16

    Three water-soluble fluorescent probes have been specifically designed to determine free cyanide concentrations up to physiologically lethal levels, >20 microM. The probes have been designed in such a way as to afford many notable sensing features, which render them unique with regard to signal transduction, photophysical characteristics, and their application to physiological cyanide determination and safeguard. The probes are readily able to reversibly bind free aqueous cyanide with dissociation constants around 4 microM3. Subsequent cyanide binding modulates the intramolecular charge transfer within the probes, a change in the electronic properties within the probes, resulting in enhanced fluorescence optical signals as a function of increased solution cyanide concentration. The ground-state chelation with cyanide produces wavelength shifts, which also enable the probes to sense cyanide in both an excitation and emission ratiometric manner, in addition to enhanced fluorescence signaling. This has enabled a generic cyanide sensing platform to be realized that is not dependent on fluorescent probe concentration, probe photodegradation, or fluctuations in the intensity of any employed excitation sources, ideal for remote cyanide sensing applications. Further, the >600 nm fluorescence emission of the probes potentially allows for enhanced fluorescence ratiometric cyanide sensing in the optical window of tissues and blood, facilitating their use for the transdermal monitoring of cyanide for mammalian safeguard or postmortem in fire victims, both areas of active research. PMID:15755185

  5. Coagulation-driven platelet activation reduces cholestatic liver injury and fibrosis in mice

    PubMed Central

    Joshi, N.; Kopec, A. K.; O’Brien, K. M.; Towery, K. L.; Cline-Fedewa, H.; Williams, K.J.; Copple, B. L.; Flick, M. J.; Luyendyk, J. P.

    2014-01-01

    Summary Background The coagulation cascade has been shown to participate in chronic liver injury and fibrosis, but the contribution of various thrombin targets, such as protease activated receptors (PARs) and fibrin(ogen), has not been fully described. Emerging evidence suggests that in some experimental settings of chronic liver injury, platelets can promote liver repair and inhibit liver fibrosis. However, the precise mechanisms linking coagulation and platelet function to hepatic tissue changes following injury remain poorly defined. Objectives To determine the role of PAR-4, a key thrombin receptor on mouse platelets, and fibrin(ogen) engagement of the platelet αIIbβ3 integrin in a model of cholestatic liver injury and fibrosis. Methods Biliary and hepatic injury was characterized following 4 week administration of the bile duct toxicant α-naphthylisothiocyanate (ANIT) (0.025%) in PAR-4-deficient mice (PAR-4−/− mice), mice expressing a mutant form of fibrin(ogen) incapable of binding integrin αIIbβ3 (FibγΔ5), and wild-type mice. Results Elevated plasma thrombin-antithrombin and serotonin levels, hepatic fibrin deposition and platelet accumulation in liver accompanied hepatocellular injury and fibrosis in ANIT-treated wild-type mice. PAR-4 deficiency reduced plasma serotonin levels, increased serum bile acid concentration, and exacerbated ANIT-induced hepatocellular injury and peribiliary fibrosis. Compared to PAR-4-deficient mice, ANIT-treated FibγΔ5 mice displayed more widespread hepatocellular necrosis accompanied by marked inflammation, robust fibroblast activation and extensive liver fibrosis. Conclusions Collectively, the results indicate that PAR-4 and fibrin-αIIbβ3 integrin engagement, pathways coupling coagulation to platelet activation, each exert hepatoprotective effects during chronic cholestasis. PMID:25353084

  6. Fish oil supplementation reduces cortisol basal levels and perceived stress: a randomized, placebo-controlled trial in abstinent alcoholics.

    PubMed

    Barbadoro, Pamela; Annino, Isidoro; Ponzio, Elisa; Romanelli, Roberto M L; D'Errico, Marcello M; Prospero, Emilia; Minelli, Andrea

    2013-06-01

    Behavioral distress and dysfunctions of hypothalamic-pituitary-adrenocortical (HPA) axis play a central role in alcohol abuse. Omega-3 fatty acids are proposed as having antistress, regulatory effects on HPA responsiveness, but a possible protective role in ethanol addiction is unexplored.A randomized, doubleblind, placebo-controlled trial was performed in male alcoholics undergoing residential rehabilitation program, to evaluate the effects of 3-week supplementation with fish-oil providing eicosapentaenoic (60 mg/day) and docosahexaenoic acid (252 mg/day) on perceived stress/anxiety and HPA activity, assessed by measuring saliva basal cortisol levels at various daytimes (0730 h, 1130 h, 1600 h, 2000 h, and 2400 h) and the acute cortisol response to Trier Social Stress Test.Results showed that in supplemented subjects, before versus after decrease of stress/anxiety ratings was accompanied by reduction of cortisol basal levels throughout the day; no changes were observed in placebo group. At the end of intervention, amplitude, and duration of stress-evoked cortisol response did not differ between groups; however, the peak of cortisol response was temporally anticipated in supplemented subjects. In conclusion, an elevated omega-3 intake may reduce distress symptoms and basal cortisol secretion in abstinent alcoholics, thus providing a valid subsidiary measure to increase the efficacy of rehabilitation programs in ethanol addicts. PMID:23390041

  7. Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro.

    PubMed

    Miyagoe-Suzuki, Yuko; Masubuchi, Nami; Miyamoto, Kaori; Wada, Michiko R; Yuasa, Shigeki; Saito, Fumiaki; Matsumura, Kiichiro; Kanesaki, Hironori; Kudo, Akira; Manya, Hiroshi; Endo, Tamao; Takeda, Shin'ichi

    2009-01-01

    Protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) is an enzyme that transfers N-acetylglucosamine to O-mannose of glycoproteins. Mutations of the POMGnT1 gene cause muscle-eye-brain (MEB) disease. To obtain a better understanding of the pathogenesis of MEB disease, we mutated the POMGnT1 gene in mice using a targeting technique. The mutant muscle showed aberrant glycosylation of alpha-DG, and alpha-DG from mutant muscle failed to bind laminin in a binding assay. POMGnT1(-/-) muscle showed minimal pathological changes with very low-serum creatine kinase levels, and had normally formed muscle basal lamina, but showed reduced muscle mass, reduced numbers of muscle fibers, and impaired muscle regeneration. Importantly, POMGnT1(-/-) satellite cells proliferated slowly, but efficiently differentiated into multinuclear myotubes in vitro. Transfer of a retrovirus vector-mediated POMGnT1 gene into POMGnT1(-/-) myoblasts completely restored the glycosylation of alpha-DG, but proliferation of the cells was not improved. Our results suggest that proper glycosylation of alpha-DG is important for maintenance of the proliferative activity of satellite cells in vivo. PMID:19114101

  8. Effect of Learning Activity on Students' Motivation, Physical Activity Levels and Effort/Persistence

    ERIC Educational Resources Information Center

    Gao, Zan; Lee, Amelia M.; Xiang, Ping; Kosma, Maria

    2011-01-01

    The type of learning activity offered in physical education may influence students' motivational beliefs, physical activity participation and effort/persistence in class. However, most empirical studies have focused on the individual level rather than on the learner-content interactions. Accordingly, the potential effects of learning activities on…

  9. Tight Chk1 Levels Control Replication Cluster Activation in Xenopus

    PubMed Central

    Wiggins, Jennifer M.; Barbosa, Pedro; Libeau, Pierre; Priam, Pierre; Narassimprakash, Hemalatha; Grodzenski, Xenia; Marheineke, Kathrin

    2015-01-01

    DNA replication in higher eukaryotes initiates at thousands of origins according to a spatio-temporal program. The ATR/Chk1 dependent replication checkpoint inhibits the activation of later firing origins. In the Xenopus in vitro system initiations are not sequence dependent and 2-5 origins are grouped in clusters that fire at different times despite a very short S phase. We have shown that the temporal program is stochastic at the level of single origins and replication clusters. It is unclear how the replication checkpoint inhibits late origins but permits origin activation in early clusters. Here, we analyze the role of Chk1 in the replication program in sperm nuclei replicating in Xenopus egg extracts by a combination of experimental and modelling approaches. After Chk1 inhibition or immunodepletion, we observed an increase of the replication extent and fork density in the presence or absence of external stress. However, overexpression of Chk1 in the absence of external replication stress inhibited DNA replication by decreasing fork densities due to lower Cdk2 kinase activity. Thus, Chk1 levels need to be tightly controlled in order to properly regulate the replication program even during normal S phase. DNA combing experiments showed that Chk1 inhibits origins outside, but not inside, already active clusters. Numerical simulations of initiation frequencies in the absence and presence of Chk1 activity are consistent with a global inhibition of origins by Chk1 at the level of clusters but need to be combined with a local repression of Chk1 action close to activated origins to fit our data. PMID:26046346

  10. An Unbalanced Rearrangement of Chromosomes 4:20 is Associated with Childhood Osteoporosis and Reduced Caspase-3 Levels.

    PubMed

    Kinning, Esther; McMillan, Martin; Shepherd, Sheila; Helfrich, Miep; Hof, Rob Vant; Adams, Christopher; Read, Heather; Wall, Daniel M; Ahmed, S Faisal

    2016-09-01

    The purpose of this study was to investigate the association of a chromosome 4:20 imbalance with osteoporosis in three related children. Bone biochemistry, bone turnover markers, and dual-energy X-ray absorptiometry (DXA) scanning were performed in all three cases and bone biopsy and histomorphometry in one. The chromosome imbalance was delineated by array comparative genomic hybridization (aCGH) and analyzed for candidate genes. A potential candidate gene within the deleted region is caspase-3, previously linked to low bone mineral density (BMD) in heterozygous mice thus caspase-3 activity was measured in cases and controls. Routine bone biochemistry and markers of bone turnover did not reveal any abnormality. DXA showed reduced total and lumbar spine bone mineral content. aCGH showed an 8 megabase (Mb) deletion of terminal chromosome 4q incorporating a region previously linked to low BMD and a 15 Mb duplication of terminal chromosome 20p. Bone biopsy showed a high bone turnover state, trabecularisation of cortical bone and numerous small osteoclasts coupled with normal bone formation. Basal serum caspase-3 activity was lower in cases compared with controls. We conclude that the early-onset osteoporosis with low basal levels of caspase-3 and abnormal osteoclasts is a feature of this chromosomal translocation. Further investigation of the role of the deleted and duplicated genes and especially caspase-3 is required. PMID:27617159

  11. Improvement of the reverse tetracycline transactivator by single amino acid substitutions that reduce leaky target gene expression to undetectable levels.

    PubMed

    Roney, Ian J; Rudner, Adam D; Couture, Jean-François; Kærn, Mads

    2016-01-01

    Conditional gene expression systems that enable inducible and reversible transcriptional control are essential research tools and have broad applications in biomedicine and biotechnology. The reverse tetracycline transcriptional activator is a canonical system for engineered gene expression control that enables graded and gratuitous modulation of target gene transcription in eukaryotes from yeast to human cell lines and transgenic animals. However, the system has a tendency to activate transcription even in the absence of tetracycline and this leaky target gene expression impedes its use. Here, we identify single amino-acid substitutions that greatly enhance the dynamic range of the system in yeast by reducing leaky transcription to undetectable levels while retaining high expression capacity in the presence of inducer. While the mutations increase the inducer concentration required for full induction, additional sensitivity-enhancing mutations can compensate for this effect and confer a high degree of robustness to the system. The novel transactivator variants will be useful in applications where tight and tunable regulation of gene expression is paramount. PMID:27323850

  12. Improvement of the reverse tetracycline transactivator by single amino acid substitutions that reduce leaky target gene expression to undetectable levels

    PubMed Central

    Roney, Ian J.; Rudner, Adam D.; Couture, Jean-François; Kærn, Mads

    2016-01-01

    Conditional gene expression systems that enable inducible and reversible transcriptional control are essential research tools and have broad applications in biomedicine and biotechnology. The reverse tetracycline transcriptional activator is a canonical system for engineered gene expression control that enables graded and gratuitous modulation of target gene transcription in eukaryotes from yeast to human cell lines and transgenic animals. However, the system has a tendency to activate transcription even in the absence of tetracycline and this leaky target gene expression impedes its use. Here, we identify single amino-acid substitutions that greatly enhance the dynamic range of the system in yeast by reducing leaky transcription to undetectable levels while retaining high expression capacity in the presence of inducer. While the mutations increase the inducer concentration required for full induction, additional sensitivity-enhancing mutations can compensate for this effect and confer a high degree of robustness to the system. The novel transactivator variants will be useful in applications where tight and tunable regulation of gene expression is paramount. PMID:27323850

  13. Microgravity: a Teacher's Guide with Activities, Secondary Level

    NASA Technical Reports Server (NTRS)

    Vogt, Gregory L. (Editor); Wargo, Michael J. (Editor)

    1992-01-01

    This NASA Educational Publication is a teacher's guide that focuses on microgravity for the secondary level student. The introduction answers the question 'What is microgravity?', as well as describing gravity and creating microgravity. Following the introduction is a microgravity primer which covers such topics as the fluid state, combustion science, materials science, biotechnology, as well as microgravity and space flight. Seven different activities are described in the activities section and are written by authors prominent in the field. The concluding sections of the book include a glossary, microgravity references, and NASA educational resources.

  14. 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

  15. Acetylcholinesterase modulates presenilin-1 levels and γ-secretase activity.

    PubMed

    Campanari, Maria-Letizia; García-Ayllón, María-Salud; Belbin, Olivia; Galcerán, Joan; Lleó, Alberto; Sáez-Valero, Javier

    2014-01-01

    The cholinergic enzyme acetylcholinesterase (AChE) and the catalytic component of the γ-secretase complex, presenilin-1 (PS1), are known to interact. In this study, we investigate the consequences of AChE-PS1 interactions, particularly the influence of AChE in PS1 levels and γ-secretase activity. PS1 is able to co-immunoprecipitate all AChE variants (AChE-R and AChE-T) and molecular forms (tetramers and light subunits) present in the human brain. Overexpression of AChE-R or AChE-T, or their respective inactive mutants, all trigger an increase in PS1 protein levels. The AChE species capable of triggering the biggest increase in PS1 levels is a complex of AChE with the membrane anchoring subunit proline-rich membrane anchor (PRiMA), which restricts the localization of the resulting AChE tetramer to the outer plasma membrane. Incubation of cultured cells with soluble AChE demonstrates that AChE is able to increase PS1 at both the protein and transcript levels. However, the increase of PS1 caused by soluble AChE is accompanied by a decrease in γ-secretase activity as shown by the reduction of the processing of the amyloid-β protein precursor. This inhibitory effect of AChE on γ-secretase activity was also demonstrated by directly assessing accumulation of CTF-AβPP in cell-free membrane preparations incubated with AChE. Our data suggest that AChE may function as an inhibitor of γ-secretase activity. PMID:24699279

  16. 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

  17. Differential metallothionein, reduced glutathione and metal levels in Perna perna mussels in two environmentally impacted tropical bays in southeastern Brazil.

    PubMed

    Lavradas, Raquel T; Rocha, Rafael C C; Bordon, Isabella C A C; Saint'Pierre, Tatiana D; Godoy, José M; Hauser-Davis, Rachel A

    2016-07-01

    Mussel farming is an important economic activity in Brazil, and these organisms are consumed by the majority of the population in most coastal zones in the country. However, despite the increasing pollution of aquatic ecosystems in Brazil, little is known about the biochemical activity in mussels in response to metal exposure. In this context, the aim of the present study was to investigate metal and metalloid exposure effects in Perna perna mussels, by determining metal levels, the induction of metallothionein (MT) synthesis, and oxidative stress, in the form of reduced glutathione (GSH) in 3 contaminated areas from the Guanabara Bay in comparison to a reference site, Ilha Grande Bay, both in summer and winter. Metal and metalloid concentrations were also compared to Brazilian and international guidelines, to verify potential health risks to human consumers. Mussels from all sampling sites were shown to be improper for human consumption due to metal contamination, including Ilha Grande Bay, which has previously been considered a reference site. Several statistically significant correlations and seasonal differences were observed between MT, GSH and metals and metalloids in both analyzed tissues. A Discriminant Canonical Analysis indicated that the digestive gland is a better bioindicator for environmental contamination by metals and metalloids in this species and offers further proof that MT variations observed are due to metal exposure and not oxidative stress, since GSH influence for both muscle tissue and the digestive glands was non-significant in this analysis. These results show that P. perna mussels are an adequate sentinel species for metal contamination with significant effects on oxidative stress and metal exposure biomarkers. To the best of our knowledge, this is the first study to report metals, metalloids, MT and GSH levels in the muscle tissue of this species. PMID:26994306

  18. 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

  19. Induction of Reduced Photorespiratory Activity in Submersed and Amphibious Aquatic Macrophytes 1

    PubMed Central

    Salvucci, Michael E.; Bowes, George

    1981-01-01

    Incubation under water in a 30 C/14-hour or 12 C/10-hour photoperiod caused the CO2 compensation points of 10 aquatic macrophytes to decrease below 25 or increase above 50 microliters CO2 per liter, respectively. Submerged and aerial leaves of two amphibious angiosperms (Myriophyllum brasiliense and Proserpinaca palustris) maintained high compensation points when incubated in air but, when the submerged or aerial leaves of Proserpinaca were incubated under water, the compensation points dropped as low as 10. This suggests that, in addition to temperature and photoperiod, some factor associated with submergence regulates the compensation point of aquatic plants. In the high-compensation point plants, photorespiration, as a percentage of net photosynthesis, was equivalent to that in terrestrial C3 plants. For Hydrilla verticillata, the decreasing CO2 compensation points (110, 40, and 10) were associated with reduced photorespiration, as indicated by decreased O2 inhibition, decreased rates of CO2 evolution into CO2-free air, and increased net photosynthetic rates. The decrease in the CO2 compensation points of Hydrilla, Egeria densa, and Cabomba caroliniana was accompanied by an increase in the activity of phosphoenolpyruvate, but not of ribulose bisphosphate, carboxylase. In Hydrilla, several C4 enzymes also increased in activity to the following levels (micromoles per gram fresh weight per hour): pyruvate Pi dikinase (35), pyrophosphatase (716), adenylate kinase (525), NAD and NADP malate dehydrogenase (6565 and 30), NAD and NADP malic enzymes (239 and 44), and aspartate and alanine aminotransferases (357 and 85), whereas glycolate oxidase (6) and phosphoglycolate and phosphoglycerate phosphatases (76 and 32) showed no change. Glycolate dehydrogenase and phosphoenolpyruvate carboxykinase were undetectable. The reduced photorespiration in these plants may be due to increased CO2 fixation via a C4 acid pathway. However, for three Myriophyllum species, some other

  20. Reduced activity of ATP synthase in mitochondria causes cytoplasmic male sterility in chili pepper.

    PubMed

    Li, Jinjie; Pandeya, Devendra; Jo, Yeong Deuk; Liu, Wing Yee; Kang, Byoung-Cheorl

    2013-04-01

    Cytoplasmic male sterility (CMS) is a maternally inherited trait characterized by the inability to produce functional pollen. The CMS-associated protein Orf507 (reported as Orf456 in previous researches) was previously identified as a candidate gene for mediating male sterility in pepper. Here, we performed yeast two-hybrid analysis to screen for interacting proteins, and found that the ATP synthase 6 kDa subunit containing a mitochondrial signal peptide (MtATP6) specifically interacted with Orf507. In addition, the two proteins were found to be interacted in vivo using bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (Co-IP) assays. Further functional characterization of Orf507 revealed that the encoded protein is toxic to bacterial cells. Analysis of tissue-specific expression of ATP synthase 6 kDa showed that the transcription level was much lower in anthers of the CMS line than in their wild type counterparts. In CMS plants, ATP synthase activity and content were reduced by more than half compared to that of the normal plants. Taken together, it can be concluded that reduced ATP synthase activity and ATP content might have affected pollen development in CMS plants. Here, we hypothesize that Orf507 might cause MtATP6 to be nonfunctional by changing the latter's conformation or producing an inhibitor that prevents the normal functioning of MtATP6. Thus, further functional analysis of mitochondrial Orf507 will provide insights into the mechanisms underlying CMS in plants. PMID:23274393

  1. 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

  2. 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

  3. Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis.

    PubMed

    Hutt, Darren M; Herman, David; Rodrigues, Ana P C; Noel, Sabrina; Pilewski, Joseph M; Matteson, Jeanne; Hoch, Ben; Kellner, Wendy; Kelly, Jeffery W; Schmidt, Andre; Thomas, Philip J; Matsumura, Yoshihiro; Skach, William R; Gentzsch, Martina; Riordan, John R; Sorscher, Eric J; Okiyoneda, Tsukasa; Yates, John R; Lukacs, Gergely L; Frizzell, Raymond A; Manning, Gerard; Gottesfeld, Joel M; Balch, William E

    2010-01-01

    Chemical modulation of histone deacetylase (HDAC) activity by HDAC inhibitors (HDACi) is an increasingly important approach for modifying the etiology of human disease. Loss-of-function diseases arise as a consequence of protein misfolding and degradation, which lead to system failures. The DeltaF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) results in the absence of the cell surface chloride channel and a loss of airway hydration, leading to the premature lung failure and reduced lifespan responsible for cystic fibrosis. We now show that the HDACi suberoylanilide hydroxamic acid (SAHA) restores surface channel activity in human primary airway epithelia to levels that are 28% of those of wild-type CFTR. Biological silencing of all known class I and II HDACs reveals that HDAC7 plays a central role in restoration of DeltaF508 function. We suggest that the tunable capacity of HDACs can be manipulated by chemical biology to counter the onset of cystic fibrosis and other human misfolding disorders. PMID:19966789

  4. Reduced Histone Deacetylase 7 Activity Restores Function to Misfolded CFTR in Cystic Fibrosis

    PubMed Central

    Hutt, Darren M.; Herman, David; Rodrigues, Ana P. C.; Noel, Sabrina; Pilewski, Joseph M.; Matteson, Jeanne; Hoch, Ben; Kellner, Wendy; Kelly, Jeffery W.; Schmidt, Andre; Thomas, Philip J.; Matsumura, Yoshihiro; Skach, William R.; Gentzsch, Martina; Riordan, John R.; Sorscher, Eric J.; Okiyoneda, Tsukasa; Lukacs, Gergely L.; Frizzell, Raymond A.; Manning, Gerard; Gottesfeld, Joel M.; Balch, William E.

    2010-01-01

    Chemical modulation of histone deacetylase (HDAC) activity by HDAC inhibitors (HDACi) is an increasingly important approach to modify the etiology of human disease. Loss-of-function diseases arise as a consequence of protein misfolding and degradation leading to system failures. The ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) results in the absence of the cell surface chloride channel and a loss of airway hydration, leading to premature lung failure and reduced lifespan responsible for cystic fibrosis (CF). We now show that the HDACi suberoylanilide hydroxamic acid (SAHA) restores surface channel activity in human primary airway epithelia to levels that are 28% of wild-type CFTR. Biological silencing of all known class I and II HDACs reveals that HDAC7 plays a central role in restoration of ΔF508 function. We suggest that the tunable capacity of HDACs can be manipulated by chemical biology to counter the onset of CF and other human misfolding disorders. PMID:19966789

  5. Computational Studies of CO2 Activation via Photochemical Reactions with Reduced Sulfur Compounds

    PubMed Central

    Baltrusaitis, Jonas; Patterson, Eric; Hatch, Courtney

    2012-01-01

    Reactions between CO2 and reduced sulfur compounds (RSC) - H2S and CH3SH - were investigated using ground and excited state density functional theory (DFT) and coupled cluster (CC) methods to explore possible RSC oxidation mechanisms and CO2 activation mechanisms in the atmospheric environment. Ground electronic state calculations at the CR-CC(2,3)/6-311+G(2df,2p)//CAM-B3LYP/6-311+G(2df,2p) level show proton transfer as a limiting step in the reduction of CO2 with activation energies of 49.64 and 47.70 kcal/mol, respectively, for H2S and CH3SH. On the first excited state surface, CR-EOMCC(2,3)/6-311+G(2df,2p)//CAM-B3LYP/6-311+G(2df,2p) calculations reveal that energies of <250 nm are needed to form H2S-CO2 and CH3SH-CO2 complexes allowing facile hydrogen atom transfer. Once excited, all reaction intermediates and transition states are downhill energetically showing either C-H or C-S bond formation in the excited state whereas only C-S bond formation was found in the ground state. Environmental implications of these data are discussed with a focus on tropospheric reactions between CO2 and RSC, as well as potential for carbon sequestration using photocatalysis. PMID:22920727

  6. 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

  7. 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

  8. 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

  9. Oxidized and Reduced Nicotinamide Adenine Dinucleotide Phosphate Levels of Plants Hardened and Unhardened Against Chilling Injury

    PubMed Central

    Kuraishi, Susumu; Arai, Noriko; Ushijima, Tadahiro; Tazaki, Tadayoshi

    1968-01-01

    Pea plants (Pisum sativum L. var. Alaska) subjected to low temperature (5°) in the light acquired resistance against chilling injury. Unhardened plants maintained high NADP and low NADPH levels during illumination at 25° but hardened plants had low NADP and high NADPH levels in the light. When the unhardened plants were transferred to the dark room at 25°, their NADPH levels decreased immediately. On the other hand, hardened plants maintained a high NADPH level for a few hours even in the dark. PMID:16656757

  10. Person-Centred Active Support--Increasing Choice, Promoting Independence and Reducing Challenging Behaviour

    ERIC Educational Resources Information Center

    Beadle-Brown, Julie; Hutchinson, Aislinn; Whelton, Beckie

    2012-01-01

    Background: Previous research has found that active support is effective at increasing levels of participation in activities and supporting a good quality of life for people with intellectual disabilities. However, there has been little research on the effect of active support on other outcome measures. Methods: This study uses observational…

  11. Visual Acuity’s Association with Levels of Leisure-Time Physical Activity Among Community-Dwelling Older Adults

    PubMed Central

    Swanson, Mark W; Bodner, Eric; Sawyer, Patricia; Allman, Richard

    2013-01-01

    Little is known about the affect of reduced vision on physical activity in older adults. This study evaluates the association of visual acuity level, self-reported vision and ocular disease conditions with leisure-time physical activity and calculated caloric expenditure. A cross sectional study of 911 subjects 65 yr and older from the University of Alabama at Birmingham Study of Aging (SOA) cohort was conducted evaluating the association of vision-related variables to weekly kilocalorie expenditure calculated from the 17-item Leisure Time Physical Activity Questionnaire. Ordinal logistic regression was used to evaluate possible associations controlling for potential confounders. In multivariate analyses, each lower step in visual acuity category below 20/50 was significantly associated with reduced odds of having a higher level of physical activity OR 0.81, 95% CI 0.67, 0.97. Reduced visual acuity appears to be independently associated with lower levels of physical activity among community-dwelling adults. PMID:21945888

  12. 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

  13. 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…

  14. 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...

  15. Prolonged fasting and cortisol reduce myostatin mRNA levels in tilapia larvae; short-term fasting elevates.

    PubMed

    Rodgers, Buel D; Weber, Gregory M; Kelley, Kevin M; Levine, Michael A

    2003-05-01

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indexes in adults, skeletal muscle myostatin mRNA levels were unaffected. By contrast, larval myostatin mRNA levels were sometimes elevated after a short-term fast and were consistently reduced with prolonged fasting. These effects were specific for myostatin, as mRNA levels of glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase were unchanged. Cortisol levels were elevated in fasted larvae with reduced myostatin mRNA, whereas in addition immersion of larvae in 1 ppm (2.8 microM) cortisol reduced myostatin mRNA in a time-dependent fashion. These results suggest that larval myostatin mRNA levels may initially rise but ultimately fall during a prolonged fast. The reduction is likely mediated by fasting-induced hypercortisolemia, indicating divergent evolutionary mechanisms of glucocorticoid regulation of myostatin mRNA, since these steroids upregulate myostatin gene expression in mammals. PMID:12676749

  16. The use of asparaginase to reduce acrylamide levels in cooked food.

    PubMed

    Xu, Fei; Oruna-Concha, Maria-Jose; Elmore, J Stephen

    2016-11-01

    Strategies proposed for reducing the formation of the suspected carcinogen acrylamide in cooked foods often rely on a reduction in the extent of the Maillard reaction, in which acrylamide is formed from the reaction between asparagine and reducing sugars. However, the Maillard reaction also provides desirable sensory attributes of cooked foods. Mitigation procedures that modify the Maillard reaction may negatively affect flavour and colour. The use of asparaginase to convert asparagine to aspartic acid may provide a means to reduce acrylamide formation, while maintaining sensory quality. This review collates research on the use of enzymes, asparaginase in particular, to mitigate acrylamide formation. Asparaginase is a powerful tool for the food industry and it is likely that its use will increase. However, the potential adverse effects of asparaginase treatment on sensory properties of cooked foods and the need to achieve sufficient enzyme-substrate contact remain areas for future research. PMID:27211635

  17. 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

  18. 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

  19. Calpain expression in lymphoid cells. Increased mRNA and protein levels after cell activation.

    PubMed

    Deshpande, R V; Goust, J M; Chakrabarti, A K; Barbosa, E; Hogan, E L; Banik, N L

    1995-02-10

    Although calpain is ubiquitously present in human tissues and is thought to play a role in demyelination, its activity is very low in resting normal lymphocytes. To determine the nature of calpain expression at the mRNA and protein levels in human lymphoid cells, we studied human T lymphocytic, B lymphocytic, and monocytic lines as well as peripheral blood mononuclear cells. Stimulation of cells with the phorbol ester phorbol myristate acetate and the calcium ionophore A23187 resulted in increased calpain mRNA and protein expression. Calpain mRNA expression is also increased in human T cells stimulated with anti-CD3. A dissociation between the increases of RNA and protein suggested that calpain could be released from the cells; the subsequent experiments showed its presence in the extracellular environment. 5,6-Dichloro-1b-D-ribofuranosylbenzimidazole, a reversible inhibitor of mRNA synthesis, reduced calpain mRNA levels by 50-67% and protein levels by 72-91%. Its removal resulted in resumption of both calpain mRNA and protein synthesis. Cycloheximide, a translational inhibitor, reduced calpain protein levels by 77-81% and calpain mRNA levels by 96% in activated THP-1 cells. Interferon-gamma induced calpain mRNA and protein in U-937 and THP-1 cells. Dexamethasone increased mRNA expression in THP-1 cells. Our results indicate that activation of lymphoid cells results in de novo synthesis and secretion of calpain. PMID:7852311

  20. Low-cost household paint abatement to reduce children's blood lead levels

    SciTech Connect

    Taha, T.; Kanarek, M.S.; Schultz, B.D.; Murphy, A.

    1999-11-01

    The purpose was to examine the effectiveness of low-cost abatement on children's blood lead levels. Blood lead was analyzed before and after abatement in 37 homes of children under 7 years old with initial blood lead levels of 25--44 {micro}g/dL. Ninety-five percent of homes were built before 1950. Abatement methods used were wet-scraping and repainting deteriorated surfaces and wrapping window wells with aluminum or vinyl. A control group was retrospectively selected. Control children were under 7 years old, had initial blood lead levels of 25--44 {micro}g/dL and a follow-up level at least 28 days afterward, and did not have abatements performed in their homes between blood lead levels. After abatement, statistically significant declines occurred in the intervention children's blood lead levels. The mean decline was 22%, 1 to 6 months after treatment. After adjustment for seasonality and child's age, the mean decline was 6.0 {micro}g/dL, or 18%. The control children's blood levels did not decline significantly. There was a mean decline of 0.25 {micro}g/dL, or 0.39%. After adjustment for seasonality and age, the mean decline for control children was 1.6 {micro}g/dL, or 1.8%. Low-cost abatement and education are effective short-term interim controls.

  1. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    PubMed

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss. PMID:26758875

  2. N-acetylcysteine reduces oxidative stress, nuclear factor-κB activity and cardiomyocyte apoptosis in heart failure

    PubMed Central

    WU, XIAO-YAN; LUO, AN-YU; ZHOU, YI-RONG; REN, JIANG-HUA

    2014-01-01

    The roles of oxidative stress on nuclear factor (NF)-κB activity and cardiomyocyte apoptosis during heart failure were examined using the antioxidant N-acetylcysteine (NAC). Heart failure was established in Japanese white rabbits with intravenous injections of doxorubicin, with ten rabbits serving as a control group. Of the rabbits with heart failure, 12 were not treated (HF group) and 13 received NAC (NAC group). Cardiac function was assessed using echocardiography and hemodynamic analysis. Myocardial cell apoptosis, apoptosis-related protein expression, NF-κBp65 expression and activity, total anti-oxidative capacity (tAOC), 8-iso-prostaglandin F2α (8-iso-PGF2α) expression and glutathione (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH levels and Bcl-2/Bax ratios as well as increased 8-iso-PGF2α levels and apoptosis were observed (all P<0.05), which were effects that were attenuated by the treatment with NAC. NF-κBp65 and iNOS levels were significantly higher and the P-IκB-α levels were significantly lower in the HF group; expression of all three proteins returned to pre-HF levels following treatment with NAC. Myocardial cell apoptosis was positively correlated with left ventricular end-diastolic pressure (LVEDP), NF-κBp65 expression and 8-iso-PGF2α levels, but negatively correlated with the maximal and minimal rates of increase in left ventricular pressure (+dp/dtmax and −dp/dtmin, respectively) and the Bcl-2/Bax ratio (all P<0.001). The 8-iso-PGF2α levels were positively correlated with LVEDP and negatively correlated with +dp/dtmax and −dp/dtmin (all P<0.001). The present study demonstrated that NAC increased the antioxidant capacity, decreased the NF-κB activation and reduced myocardial cell apoptosis in an in vivo heart failure model. PMID:24889421

  3. Low-Level Laser Therapy (808 nm) Reduces Inflammatory Response and Oxidative Stress in Rat Tibialis Anterior Muscle After Cryolesion

    PubMed Central

    Assis, Lívia; Moretti, Ana I.S.; Abrahão, Thalita B.; Cury, Vivian; Souza, Heraldo P.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2012-01-01

    Background and Objective Muscle regeneration is a complex phenomenon, involving coordinated activation of several cellular responses. During this process, oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response. Among the therapeutic approaches to attenuate inflammation and increase tissue repair, low-level laser therapy (LLLT) may be a safe and effective clinical procedure. The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior (TA) muscle in rats. Material and Methods Sixty Wistar rats were randomly divided into three groups (n = 20): control (BC), injured TA muscle without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region was irradiated daily for 4 consecutive days, starting immediately after the lesion using a AlGaAs laser (continuous wave, 808 nm, tip area of 0.00785 cm2, power 30 mW, application time 47 seconds, fluence 180 J/cm2; 3.8 mW/cm2; and total energy 1.4 J). The animals were sacrificed on the fourth day after injury. Results LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid peroxidation, nitrotyrosine formation and NO production, probably due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene expression, and decreased the inflammatory response as measured by gene expression of NF-kβ and COX-2 and by TNF-α and IL-1β concentration. Conclusion These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle. PMID:23001637

  4. [Experience in reducing the levels of raticides during open area disinfestations].

    PubMed

    Turyshev, A G; Korneev, A G; Konstantinova, E L

    2009-01-01

    The experience in combining disinfestation and forestry engineering measures is described to achieve a long-term effect: in minimizing the number of murine rodents, which has considerably reduced the amount of poisoned baits placed into the environment when disinfestation is made in open areas. PMID:19802943

  5. Low-Level Mechanical Vibrations can Reduce Bone Resorption and Enhance Bone Formation in the Growing Skeleton

    SciTech Connect

    Xie,L.; Jacobsen, J.; Busa, B.; Donahue, L.; Miller, L.; Rubin, C.; Judex, S.

    2006-01-01

    Short durations of extremely small magnitude, high-frequency, mechanical stimuli can promote anabolic activity in the adult skeleton. Here, it is determined if such signals can influence trabecular and cortical formative and resorptive activity in the growing skeleton, if the newly formed bone is of high quality, and if the insertion of rest periods during the loading phase would enhance the efficacy of the mechanical regimen. Eight-week-old female BALB/cByJ mice were divided into four groups, baseline control (n = 8), age-matched control (n = 10), whole-body vibration (WBV) at 45 Hz (0.3 g) for 15 min day{sup -1} (n = 10), and WBV that were interrupted every second by 10 of rest (WBV-R, n = 10). In vivo strain gaging of two additional mice indicated that the mechanical signal induced strain oscillations of approximately 10 microstrain on the periosteal surface of the proximal tibia. After 3 weeks of WBV, applied for 15 min each day, osteoclastic activity in the trabecular metaphysis and epiphysis of the tibia was 33% and 31% lower (P < 0.05) than in age-matched controls. Bone formation rates (BFR{center_dot}BS{sup -1}) on the endocortical surface of the metaphysis were 30% greater (P < 0.05) in WBV than in age-matched control mice but trabecular and middiaphyseal BFR were not significantly altered. The insertion of rest periods (WBV-R) failed to potentiate the cellular effects. Three weeks of either WBV or WBV-R did not negatively influence body mass, bone length, or chemical bone matrix properties of the tibia. These data indicate that in the growing skeleton, short daily periods of extremely small, high-frequency mechanical signals can inhibit trabecular bone resorption, site specifically attenuate the declining levels of bone formation, and maintain a high level of matrix quality. If WBV prove to be efficacious in the growing human skeleton, they may be able to provide the basis for a non-pharmacological and safe means to increase peak bone mass and, ultimately

  6. 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

  7. Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis

    PubMed Central

    Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

    2013-01-01

    Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

  8. Reducing the substrate dependent scanner leveling effect in low-k1 contact printing

    NASA Astrophysics Data System (ADS)

    Chang, C. S.; Tseng, C. F.; Huang, C. H.; Yang, Elvis; Yang, T. H.; Chen, K. C.

    2015-03-01

    As the scaling down of design rule for high-density memory device, the small depth of focus (DoF) budget may be deteriorated by focus leveling errors, which arises in unpredicted reflectivity from multilayer structures on the topographic wafer. The leveling sensors of ASML scanner use near infrared (NIR) range wavelength which can penetrate through most of films using in semiconductor fabrication such as photo-resist, bottom anti reflective coating (BARC) and dielectric materials. Consequently, the reflected light from underlying substructures would disturb leveling sensors from accurate leveling. The different pattern densities and layout characteristics between array and periphery of a memory chip are expected to result in different leveling signals. Furthermore, the process dependent variations between wafer central and edge areas are also considered to yield different leveling performances during wafer exposure. In this study, lower blind contact immunity was observed for peripheral contacts comparing to the array contacts especially around wafer edge region. In order to overcome this problem, a series of investigations have been carried out. The wafer edge leveling optimization through circuit dependent focus edge clearance (CDFEC) option doesn't get improvement. Air gauge improved process leveling (AGILE) function of ASML immersion scanner doesn't show improved result either. The ILD uniformity improvement and step height treatments around wafer edge such as edge exclusion of film deposition and bevel etching are also ineffective to mitigate the blind contact problem of peripheral patterns. Altering the etch hard-mask stack is finally found to be an effective approach to alleviate the issue. For instance, through either containing high temperature deposition advanced patterning film (APF) in the hard-mask or inserting higher opaque film such as amorphous Si in between the hard-mask stack.

  9. 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

  10. Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application.

    PubMed

    Armanini, Decio; Nacamulli, Davide; Francini-Pesenti, Francesco; Battagin, Giuliana; Ragazzi, Eugenio; Fiore, Cristina

    2005-07-01

    Cortisol is involved in the distribution and deposition of fat, and its action is regulated by the activity of 11beta-hydroxysteroid dehydrogenase. Glycyrrhetinic acid, the active principle of licorice root, blocks 11beta-hydroxysteroid dehydrogenase type 1, thus reducing the availability of cortisol at the level of adipocytes. We evaluated the effect of topical application of a cream containing glycyrrhetinic acid in the thickness of fat at the level of the thigh. Eighteen healthy women (age range 20-33 years) with normal BMI were randomly allocated to treatment, at the level of the dominant thigh, with a cream containing 2.5% glycyrrhetinic acid (n=9) or with a placebo cream containing the excipients alone (n=9). Before and after 1 month of treatment both the circumference and the thickness of the superficial fat layer of the thighs (by ultrasound analysis) were measured. The circumference and the thickness of the superficial fat layer were significantly reduced in comparison to the controlateral untreated thigh and to control subjects treated with the placebo cream. No changes were observed in blood pressure, plasma renin activity, plasma aldosterone or cortisol. The effect of glycyrrhetinic acid on the thickness of subcutaneous fat was likely related to a block of 11beta-hydroxysteroid dehydrogenase type 1 at the level of fat cells; therefore, glycyrrhetinic acid could be effectively used in the reduction of unwanted local fat accumulation. PMID:15894038

  11. Depression-like behavior and reduced plasma testosterone levels in the senescence-accelerated mouse.

    PubMed

    Egashira, Nobuaki; Koushi, Emi; Okuno, Ryoko; Shirakawa, Atsunori; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro

    2010-05-01

    During aging, levels of testosterone gradually decline in men and low levels of testosterone in aged men are accompanied by increased incidence of depressive disorders. The senescence-accelerated-prone mouse 10 (SAMP10) is well known as an animal model of aging. The purpose of this study was to investigate the motor function, anxiety levels, depression-related emotional responses, attentional function and plasma levels of testosterone and dehydroepiandrosterone (DHEA) in SAMP10. SAMP10 exhibited a significant prolongation of immobility time compared to that of the aged-matched control senescence-accelerated-resistant mouse 1 (SAMR1) in the tail suspension test for measuring depression. Moreover, significant low levels of plasma testosterone but not DHEA were found in SAMP10, and the testosterone levels were inversely correlated with the depression-like behavior. By contrast, we did not observe any significant differences between SAMP10 and SAMR1 in the open-field, rota-rod, elevated plus-maze, marble-burying behavior, or prepulse inhibition test. The results of the present study indicate that testosterone may play an important role in the depression-like behavior in SAMP10. PMID:20117148

  12. A national project to evaluate and reduce high sound pressure levels from music.

    PubMed

    Ryberg, Johanna Bengtsson

    2009-01-01

    The highest recommended sound pressure levels for leisure sounds (music) in Sweden are 100 dB LAeq and 115 dB LAFmax for adults, and 97 dB LAeq and 110 dB LAFmax where children under the age of 13 have access. For arrangements intended for children, levels should be consistently less than 90 dB LAeq. In 2005, a national project was carried out with the aim of improving environments with high sound pressure levels from music, such as concert halls, restaurants, and cinemas. The project covered both live and recorded music. Of Sweden's 290 municipalities, 134 took part in the project, and 93 of these carried out sound measurements. Four hundred and seventy one establishments were investigated, 24% of which exceeded the highest recommended sound pressure levels for leisure sounds in Sweden. Of festival and concert events, 42% exceeded the recommended levels. Those who visit music events/establishments thus run a relatively high risk of exposure to harmful sound levels. Continued supervision in this field is therefore crucial. PMID:19414933

  13. Do biofuel blending mandates reduce gasoline consumption? Implications of state-level renewable fuel standards for energy security

    NASA Astrophysics Data System (ADS)

    Lim, Shinling

    In an effort to keep America's addiction to oil under control, federal and state governments have implemented a variety of policy measures including those that determine the composition of motor gasoline sold at the pump. Biofuel blending mandates known as Renewable Fuel Standards (RFS) are designed to reduce the amount of foreign crude oil needed to be imported as well as to boost the local ethanol and corn industry. Yet beyond looking at changes in gasoline prices associated with increased ethanol production, there have been no empirical studies that examine effects of state-level RFS implementation on gasoline consumption. I estimate a Generalized Least Squares model for the gasoline demand for the 1993 to 2010 period with state and time fixed effects controlling for RFS. States with active RFS are Minnesota, Hawaii, Missouri, Florida, Washington, and Oregon. I find that, despite the onset of federal biofuel mandates across states in 2007 and the lower energy content of blended gasoline, being in a state that has implemented RFS is associated with 1.5% decrease in gasoline consumption (including blended gasoline). This is encouraging evidence for efforts to lessen dependence on gasoline and has positive implications for energy security.

  14. PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: alirocumab.

    PubMed

    Dahagam, Chanukya; Goud, Aditya; Abdelqader, Abdelhai; Hendrani, Aditya; Feinstein, Matthew J; Qamar, Arman; Joshi, Parag H; Swiger, Kristopher J; Byrne, Kathleen; Quispe, Renato; Jones, Steven R; Blumenthal, Roger S; Martin, Seth S

    2016-03-01

    In this review, we examine alirocumab (Praluent(®)), a monoclonal antibody to PCSK9 and its role in reducing LDL-C levels. By comparing the results of various studies and trials we discuss the efficacy and safety of alirocumab. We aim to guide clinicians of the role of alirocumab in clinical practice. Overall, PCSK9 inhibitors are promising new agents in further reducing LDL-C levels in addition to diet and maximally tolerated statin therapy. Long-term outcome studies are currently ongoing and will further delineate the role of PCSK9 inhibitors. PMID:26911710

  15. Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness.

    PubMed

    Rao, Anjali; Sorkin, Alexander; Zahniser, Nancy R

    2013-10-01

    Variations in the expression levels of the dopamine transporter (DAT) can influence responsiveness to psychostimulant drugs like cocaine. To better understand this relationship, we studied a new DAT-low expresser (DAT-LE) mouse model and performed behavioral and biochemical studies with it. Immunoblotting and [(3) H]WIN 35,428 binding analyses revealed that these mice express ∼35% of wildtype (WT) mouse striatal DAT levels. Compared to WT mice, DAT-LE mice were hyperactive in a novel open-field environment. Despite their higher basal locomotor activity, cocaine (10 or 20 mg/kg, i.p.) induced greater locomotor activation in DAT-LE mice than in WT mice. The maximal velocity (Vmax ) of DAT-mediated [(3) H]DA uptake into striatal synaptosomes was reduced by 46% in DAT-LE mice, as compared to WT. Overall, considering the reduced number of DAT binding sites (Bmax ) along with the reduced Vmax in DAT-LE mice, a 2-fold increase in DA uptake turnover rate (Vmax /Bmax ) was found, relative to WT mice. This suggests that neuroadaptive changes have occurred in the DAT-LE mice that would help to compensate for their low DAT numbers. Interestingly, these changes do not include a reduction in tyrosine hydroxylase levels, as was previously reported in DAT knockout homozygous and heterozygous animals. Further, these changes are not sufficient to prevent elevated novelty- and cocaine-induced locomotor activity. Hence, these mice represent a unique model for studying changes of in vivo DAT function and regulation that result from markedly reduced levels of DAT expression. PMID:23564231

  16. Reduced photoinhibition under low irradiance enhanced Kacip Fatimah (Labisia pumila Benth) secondary metabolites, phenyl alanine lyase and antioxidant activity.

    PubMed

    Ibrahim, Mohd Hafiz; Jaafar, Hawa Z E

    2012-01-01

    A randomized complete block design experiment was designed to characterize the relationship between production of total flavonoids and phenolics, anthocyanin, photosynthesis, maximum efficiency of photosystem II (Fv/Fm), electron transfer rate (Fm/Fo), phenyl alanine lyase activity (PAL) and antioxidant (DPPH) in Labisia pumila var. alata, under four levels of irradiance (225, 500, 625 and 900 μmol/m(2)/s) for 16 weeks. As irradiance levels increased from 225 to 900 μmol/m(2)/s, the production of plant secondary metabolites (total flavonoids, phenolics and antocyanin) was found to decrease steadily. Production of total flavonoids and phenolics reached their peaks under 225 followed by 500, 625 and 900 μmol/m(2)/s irradiances. Significant positive correlation of production of total phenolics, flavonoids and antocyanin content with Fv/Fm, Fm/Fo and photosynthesis indicated up-regulation of carbon-based secondary metabolites (CBSM) under reduced photoinhibition on the under low light levels condition. At the lowest irradiance levels, Labisia pumila extracts also exhibited a significantly higher antioxidant activity (DPPH) than under high irradiance. The improved antioxidative activity under low light levels might be due to high availability of total flavonoids, phenolics and anthocyanin content in the plant extract. It was also found that an increase in the production of CBSM was due to high PAL activity under low light, probably signifying more availability of phenylalanine (Phe) under this condition. PMID:22754297

  17. Reduced Photoinhibition under Low Irradiance Enhanced Kacip Fatimah (Labisia pumila Benth) Secondary Metabolites, Phenyl Alanine Lyase and Antioxidant Activity

    PubMed Central

    Ibrahim, Mohd Hafiz; Jaafar, Hawa Z.E.

    2012-01-01

    A randomized complete block design experiment was designed to characterize the relationship between production of total flavonoids and phenolics, anthocyanin, photosynthesis, maximum efficiency of photosystem II (Fv/Fm), electron transfer rate (Fm/Fo), phenyl alanine lyase activity (PAL) and antioxidant (DPPH) in Labisia pumila var. alata, under four levels of irradiance (225, 500, 625 and 900 μmol/m2/s) for 16 weeks. As irradiance levels increased from 225 to 900 μmol/m2/s, the production of plant secondary metabolites (total flavonoids, phenolics and antocyanin) was found to decrease steadily. Production of total flavonoids and phenolics reached their peaks under 225 followed by 500, 625 and 900 μmol/m2/s irradiances. Significant positive correlation of production of total phenolics, flavonoids and antocyanin content with Fv/Fm, Fm/Fo and photosynthesis indicated up-regulation of carbon-based secondary metabolites (CBSM) under reduced photoinhibition on the under low light levels condition. At the lowest irradiance levels, Labisia pumila extracts also exhibited a significantly higher antioxidant activity (DPPH) than under high irradiance. The improved antioxidative activity under low light levels might be due to high availability of total flavonoids, phenolics and anthocyanin content in the plant extract. It was also found that an increase in the production of CBSM was due to high PAL activity under low light, probably signifying more availability of phenylalanine (Phe) under this condition. PMID:22754297

  18. Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content

    PubMed Central

    Lee, Do Kyung; Jang, Seok; Baek, Eun Hye; Kim, Mi Jin; Lee, Kyung Soon; Shin, Hea Soon; Chung, Myung Jun; Kim, Jin Eung; Lee, Kang Oh; Ha, Nam Joo

    2009-01-01

    Background Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether Bifidobacteria isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content. Methods In vitro culture experiments were performed to evaluate the ability of Bifidobacterium spp. isolated from healthy Koreans (20~30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (108~109 CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks. Results B. longum SPM1207 reduced serum total cholesterol and LDL levels significantly (p < 0.05), and slightly increased serum HDL. B. longum SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities. Conclusion Daily consumption of B. longum SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation. PMID:19515264

  19. Level and length of cyclic solar activity during the Maunder minimum as deduced from the active-day statistics

    NASA Astrophysics Data System (ADS)

    Vaquero, J. M.; Kovaltsov, G. A.; Usoskin, I. G.; Carrasco, V. M. S.; Gallego, M. C.

    2015-05-01

    Aims: The Maunder minimum (MM) of greatly reduced solar activity took place in 1645-1715, but the exact level of sunspot activity is uncertain because it is based, to a large extent, on historical generic statements of the absence of spots on the Sun. Using a conservative approach, we aim to assess the level and length of solar cycle during the MM on the basis of direct historical records by astronomers of that time. Methods: A database of the active and inactive days (days with and without recorded sunspots on the solar disc) is constructed for three models of different levels of conservatism (loose, optimum, and strict models) regarding generic no-spot records. We used the active day fraction to estimate the group sunspot number during the MM. Results: A clear cyclic variability is found throughout the MM with peaks at around 1655-1657, 1675, 1684, 1705, and possibly 1666, with the active-day fraction not exceeding 0.2, 0.3, or 0.4 during the core MM, for the three models. Estimated sunspot numbers are found to be very low in accordance with a grand minimum of solar activity. Conclusions: For the core MM (1650-1700), we have found that (1) A large portion of no-spot records, which correspond to the solar meridian observations, may be unreliable in the conventional database. (2) The active-day fraction remained low (below 0.3-0.4) throughout the MM, indicating the low level of sunspot activity. (3) The solar cycle appears clearly during the core MM. (4) The length of the solar cycle during the core MM appears for 9 ± 1 years, but this is uncertain. (5) The magnitude of the sunspot cycle during MM is assessed to be below 5-10 in sunspot numbers. A hypothesis of the high solar cycles during the MM is not confirmed.

  20. The application of high-pressure treatment in the reduction of salt levels in reduced-phosphate breakfast sausages.

    PubMed

    O'Flynn, Claire C; Cruz-Romero, Malco C; Troy, Declan; Mullen, Anne M; Kerry, Joe P

    2014-03-01

    This study investigated the effects of high pressure (HP) treatment of pork meat before manufacturing sausages with reduced salt levels and compared them to sausages manufactured with untreated meat (control sausages). A 2×5 factorial design was set up incorporating two pressure levels (0 or 150 MPa) and five salt levels (0.5, 1.0, 1.5, 2.0 and 2.5%). Most quality attributes were affected when salt levels were reduced below 1.5%. Fat loss (FL) was (P<0.05) affected by salt level; samples with <1.5% salt had the highest FL. HP treatment increased emulsion stability and reduced cook loss (CL) compared to control sausages. Increased CL was observed when salt was reduced below 2.0%. Salt reduction below 1.5% adversely affected colour, sensory and texture attributes. Independent of salt, HP treatment affected adversely juiciness and cohesiveness while adhesiveness was improved. Overall, there is potential to manufacture sausages maintaining organoleptic and functional properties traditionally associated with sausages using HP treated meat. PMID:24334049

  1. Exploring human epileptic activity at the single-neuron level.

    PubMed

    Tankus, Ariel

    2016-05-01

    Today, localization of the seizure focus heavily relies on EEG monitoring (scalp or intracranial). However, current technology enables much finer resolutions. The activity of hundreds of single neurons in the human brain can now be simultaneously explored before, during, and after a seizure or in association with an interictal discharge. This technology opens up new horizons to understanding epilepsy at a completely new level. This review therefore begins with a brief description of the basis of the technology, the microelectrodes, and the setup for their implantation in patients with epilepsy. Using these electrodes, recent studies provide novel insights into both the time domain and firing patterns of epileptic activity of single neurons. In the time domain, seizure-related activity may occur even minutes before seizure onset (in its current, EEG-based definition). Seizure-related neuronal interactions exhibit complex heterogeneous dynamics. In the seizure-onset zone, changes in firing patterns correlate with cell loss; in the penumbra, neurons maintain their spike stereotypy during a seizure. Hence, investigation of the extracellular electrical activity is expected to provide a better understanding of the mechanisms underlying the disease; it may, in the future, serve for a more accurate localization of the seizure focus; and it may also be employed to predict the occurrence of seizures prior to their behavioral manifestation in order to administer automatic therapeutic interventions. PMID:26994366

  2. Relationship between immunoglobulin levels and extremes of solar activity

    NASA Astrophysics Data System (ADS)

    Stoupel, Elijahu G.; Abramson, Eugene; Gabbay, Uri; Pick, Albert I.

    1995-06-01

    The possible relationship between epidemics and extremes of solar activity has been discussed previously. The purpose of the present study was to verify whether differences in the levels of immunoglobulins (IgA, IgG, IgM) could be noted at the highest (July 1989) and lowest (September 1986) points of the last (21st) and present (22nd) 11-year solar cycle. The work was divided into a 1-month study (covering the month of minimal or maximal solar activity), a 3-month study (1 month before and after the month of minimal or maximal solar activity) and a 5-month study (2 months before and after the month of minimal or maximal solar activity). A trend of a drop-off for all three immunoglobulins was seen on the far side of the maximal point of the solar cycle. Statistical significance was achieved in the 5-month study for IgM ( P=0.04), and a strong trend was shown for IgG ( P=0.07). Differences between the sexes were also noted.

  3. 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

  4. 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.

  5. 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

  6. Hydrophobic carboxy-terminal residues dramatically reduce protein levels in the haloarchaeon Haloferax volcanii

    PubMed Central

    Reuter, Christopher J.; Uthandi, Sivakumar; Puentes, Jose A.; Maupin-Furlow, Julie A.

    2010-01-01

    Proteolysis is important not only to cell physiology but also to the successful development of biocatalysts. While a wide-variety of signals are known to trigger protein degradation in bacteria and eukaryotes, these mechanisms are poorly understood in archaea, known for their ability to withstand harsh conditions. Here we present a systematic study in which single C-terminal amino acid residues were added to a reporter protein and shown to influence its levels in an archaeal cell. All 20 amino acid residues were examined for their impact on protein levels, using the reporter protein soluble modified red-shifted GFP (smRS-GFP) expressed in the haloarchaeon Haloferax volcanii as a model system. Addition of hydrophobic residues, including Leu, Cys, Met, Phe, Ala, Tyr, Ile and Val, gave the most pronounced reduction in smRS-GFP levels compared with the addition of either neutral or charged hydrophilic residues. In contrast to the altered protein levels, the C-terminal alterations had no influence on smRS-GFP-specific transcript levels, thus revealing that the effect is post-transcriptional. PMID:19850616

  7. Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.

    PubMed

    Gato, Nobuki; Kadowaki, Akio; Hashimoto, Natsumi; Yokoyama, Shin-ichiro; Matsumoto, Kenji

    2013-01-01

    Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia. PMID:23171573

  8. Use of cationic polymers to reduce pathogen levels during dairy manure separation.

    PubMed

    Liu, Zong; Carroll, Zachary S; Long, Sharon C; Gunasekaran, Sundaram; Runge, Troy

    2016-01-15

    Various separation technologies are used to deal with the enormous amounts of animal waste that large livestock operations generate. When the recycled waste stream is land applied, it is essential to lower the pathogen load to safeguard the health of livestock and humans. We investigated whether cationic polymers, used as a flocculent in the solid/liquid separation process, could reduce the pathogen indicator load in the animal waste stream. The effects of low charge density cationic polyacrylamide (CPAM) and high charge density cationic polydicyandiamide (PDCD) were investigated. Results demonstrated that CPAM was more effective than PDCD for manure coagulation and flocculation, while PDCD was more effective than CPAM in reducing the pathogen indicator loads. However, their combined use, CPAM followed by PDCD, resulted in both improved solids separation and pathogen indicator reduction. PMID:26513324

  9. Future development programs. [for defining the emission problem and developing hardware to reduce pollutant levels

    NASA Technical Reports Server (NTRS)

    Jedrziewski, S.

    1976-01-01

    The emission problem or source points were defined and new materials, hardware, or operational procedures were developed to exercise the trends defined by the data collected. The programs to reduce the emission output of aircraft powerplants were listed. Continued establishment of baseline emissions for various engine models, continued characterization of effect of production tolerances on emissions, carbureted engine development and flight tests, and cylinder cooling/fin design programs were several of the programs investigated.

  10. Could low dead-space syringes really reduce HIV transmission to low levels?

    PubMed

    Vickerman, P; Martin, N K; Hickman, M

    2013-01-01

    Studies published by Zule and colleagues have suggested that use of low dead-space syringes (LDSS) instead of high dead-space syringes (HDSS) by injecting drug users (IDUs) could dramatically reduce HIV transmission. However, evidence is limited because experiments have considered a small range of syringe types and have been unable to reliably estimate the efficacy of using LDSS for reducing HIV transmission. We critically appraise available evidence to determine whether using LDSS is likely to dramatically reduce HIV transmission. We systematically review the literature on the dead-space volume of syringes and estimate the factor difference in blood volume transferred from sharing LDSS or HDSS. Existing data on the relationship between host viral load and HIV transmission risk is used to evaluate the likely efficacy of using LDSS instead of HDSS. An HIV transmission model is used to make conservative impact projections for switching to using LDSS, and explore the implications of heterogeneity in IDU transmission risk and syringe preferences. Although highly variable, reviewed studies suggest that HDSS have on average 10 times the dead-space volume of LDSS and could result in 6/54/489 times more blood being transferred after 0/1/2 water rinses. Assuming a conservative 2-fold increase in HIV transmission risk per 10-fold increase in infected blood inoculum, HDSS use could be associated with a mean 1.7/3.6/6.5-fold increase in transmission risk compared to LDSS for 0/1/2 rinses. However, even for a low efficacy estimate, modelling suggests that partially transferring to LDSS use from using HDSS could dramatically reduce HIV prevalence (generally >33% if LDSS use is 50%), but impact will depend on IDU behavioural heterogeneity and syringe preference. Indirect evidence suggests that encouraging HDSS users to use LDSS could be a powerful HIV prevention strategy. There is an urgent need to evaluate the real life effectiveness of this strategy. PMID:23206493

  11. Reduced topoisomerase II activity in multidrug-resistant human non-small cell lung cancer cell lines.

    PubMed Central

    Eijdems, E. W.; de Haas, M.; Timmerman, A. J.; Van der Schans, G. P.; Kamst, E.; de Nooij, J.; Astaldi Ricotti, G. C.; Borst, P.; Baas, F.

    1995-01-01

    Multidrug-resistant (MDR) cell lines often have a compound phenotype, combining reduced drug accumulation with a decrease in topoisomerase II. We have analysed alterations in topoisomerase II in MDR derivatives of the human lung cancer cell line SW-1573. Selection with doxorubicin frequently resulted in reduced topo II alpha mRNA and protein levels, whereas clones selected with vincristine showed normal levels of topo II alpha. No alterations of topo II beta levels were detected. To determine the contribution of topo II alterations to drug resistance, topo II activity was analysed by the determination of DNA breaks induced by the topo II-inhibiting drug 4'-(9-acridinylamino)methane-sulphon-m-anisidide (m-AMSA) in living cells, as m-AMSA is not affected by the drug efflux mechanism in the SW-1573 cells. The number of m-AMSA-induced DNA breaks correlated well (r = 0.96) with in vitro m-AMSA sensitivity. Drug sensitivity, however, did not always correlate with reduced topo II mRNA or protein levels. In one of the five doxorubicin-selected clones m-AMSA resistance and a reduction in m-AMSA-induced DNA breaks were found in the absence of reduced topo II protein levels. Therefore, we assume that post-translational modifications of topo II also contribute to drug resistance in SW-1573 cells. These results suggest that methods that detect quantitative as well as qualitative alterations of topo II should be used to predict the responsiveness of tumours to cytotoxic agents. The assay we used, which measures DNA breaks as an end point of topo II activity, could be a good candidate. Images Figure 1 Figure 2 Figure 4 PMID:7819046

  12. Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs.

    PubMed

    Vhile, S G; Kjos, N P; Sørum, H; Overland, M

    2012-05-01

    Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH. PMID:22558928

  13. The development of ferritic-martensitic steels with reduced long-term activation

    NASA Astrophysics Data System (ADS)

    Ehrlich, K.; Kelzenberg, S.; Röhrig, H.-D.; Schäfer, L.; Schirra, M.

    1994-09-01

    Ferritic-martensitic 9-12% CrMoVNb steels of MANET type possess a number of advantageous properties for fusion reactor application. Their optimization has led to improved creep and fracture-toughness properties. New 9-10% CrWVTa alloys have been developed by KfK/IMF in collaboration with the SAARSTAHL GmbH which have a reduced long-term activation and show in addition superior fracture toughness properties. The calculation of dose rate and other radiological parameters with the presently available FISPACT/EAF codes, extended by KfK files for sequential reactions has shown that the long-term dose-rate in these alloys is governed by the remaining 'impurity level' of Nb and the alloying elements W and Ta. Sequential reactions — though relevant for single alloying elements like Cr, Mn, V and N — provide only a second order effect in Fe-based alloys. A challenge for the future materials development is the production of alloys with the desired narrow specification of elements and impurities, which necessitates new ways of steelmaking.

  14. Activity of Medicinal Plant Extracts on Multiplication of Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic Assays

    PubMed Central

    Bhatter, Purva D.; Gupta, Pooja D.; Birdi, Tannaz J.

    2016-01-01

    Aim. Test the activity of selected medicinal plant extracts on multiplication of Mycobacterium tuberculosis under reduced oxygen concentration which represents nonreplicating conditions. Material and Methods. Acetone, ethanol and aqueous extracts of the plants Acorus calamus L. (rhizome), Ocimum sanctum L. (leaf), Piper nigrum L. (seed), and Pueraria tuberosa DC. (tuber) were tested on Mycobacterium tuberculosis H37Rv intracellularly using an epithelial cell (A549) infection model. The extracts found to be active intracellularly were further studied axenically under reducing oxygen concentrations. Results and Conclusions. Intracellular multiplication was inhibited ≥60% by five of the twelve extracts. Amongst these 5 extracts, in axenic culture, P. nigrum (acetone) was active under aerobic, microaerophilic, and anaerobic conditions indicating presence of multiple components acting at different levels and P. tuberosa (aqueous) showed bactericidal activity under microaerophilic and anaerobic conditions implying the influence of anaerobiosis on its efficacy. P. nigrum (aqueous) and A. calamus (aqueous and ethanol) extracts were not active under axenic conditions but only inhibited intracellular growth of Mycobacterium tuberculosis, suggesting activation of host defense mechanisms to mediate bacterial killing rather than direct bactericidal activity. PMID:26941797

  15. Activity of Medicinal Plant Extracts on Multiplication of Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic Assays.

    PubMed

    Bhatter, Purva D; Gupta, Pooja D; Birdi, Tannaz J

    2016-01-01

    Aim. Test the activity of selected medicinal plant extracts on multiplication of Mycobacterium tuberculosis under reduced oxygen concentration which represents nonreplicating conditions. Material and Methods. Acetone, ethanol and aqueous extracts of the plants Acorus calamus L. (rhizome), Ocimum sanctum L. (leaf), Piper nigrum L. (seed), and Pueraria tuberosa DC. (tuber) were tested on Mycobacterium tuberculosis H37Rv intracellularly using an epithelial cell (A549) infection model. The extracts found to be active intracellularly were further studied axenically under reducing oxygen concentrations. Results and Conclusions. Intracellular multiplication was inhibited ≥60% by five of the twelve extracts. Amongst these 5 extracts, in axenic culture, P. nigrum (acetone) was active under aerobic, microaerophilic, and anaerobic conditions indicating presence of multiple components acting at different levels and P. tuberosa (aqueous) showed bactericidal activity under microaerophilic and anaerobic conditions implying the influence of anaerobiosis on its efficacy. P. nigrum (aqueous) and A. calamus (aqueous and ethanol) extracts were not active under axenic conditions but only inhibited intracellular growth of Mycobacterium tuberculosis, suggesting activation of host defense mechanisms to mediate bacterial killing rather than direct bactericidal activity. PMID:26941797

  16. INCREASING SAFETY AND REDUCING ENVIRONMENTAL DAMAGE RISK FROM AGING HIGH-LEVEL RADIOACTIVE WASTE TANKS

    EPA Science Inventory

    There exists a paramount need for improved understanding of the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program, which at the time of this writing is in its early stage...

  17. The mathematical model reduces the effect of distance to the scatter images gray level

    NASA Astrophysics Data System (ADS)

    Sun, Li-na

    2013-09-01

    In x-ray scanning system, scatter images are obtained to provide information on material density. The forward and backward scatter is related to solid angle. Scatter is therefore dependent on the distance of the scanned object from the x-ray source. In the real world, an object may be placed anywhere on the conveyer belt, so the measured intensity will contain errors relative to the ideal intensity. This makes classification results less reliable. Extraction of characteristic values L associated with the density; need to know the gray levels of scatter images, so how to base on forward scatter and back scatter images to determine the scatter image gray level is first necessary to solve the problem. The author combined with the forward scatter and backscatter images,then established higher order gray-level mathematical model of scattering images, to eliminate the impact of distance on the scatter images, to obtain more accurate gray level of scatter image. Then compare the error use of LMS algorithm and the LS algorithm to solving mathematical model parameters, LS algorithm ultimately prove less error and experimental validation of the superiority of the LS algorithm.

  18. Phosphorothioate Oligonucleotides Reduce PrPSc Levels and Prion Infectivity in Cultured Cells

    PubMed Central

    Karpuj, Marcela V; Giles, Kurt; Gelibter-Niv, Sagit; Scott, Michael R; Lingappa, Vishwanath R; Szoka, Francis C; Peretz, David; Denetclaw, Wilfred; Prusiner, Stanley B

    2007-01-01

    Prions are composed solely of the disease-causing prion protein (PrPSc) that is formed from the cellular isoform PrPC by a posttranslational process. Here we report that short phosphorothioate DNA (PS-DNA) oligonucleotides diminished the levels of both PrPC and PrPSc in prion-infected neuroblastoma (ScN2a) cells. The effect of PS-DNA on PrP levels was independent of the nucleotide sequence. The effective concentration (EC50) of PS-DNA required to achieve half-maximal diminution of PrPSc was ~70 nM, whereas the EC50 of PS-DNA for PrPC was more than 50-fold greater. This finding indicated that diminished levels of PrPSc after exposure to PS-DNA are unlikely to be due to decreased PrPC levels. Bioassays in transgenic mice demonstrated a substantial diminution in the prion infectivity after ScN2a cells were exposed to PS-DNAs. Whether PS-DNA will be useful in the treatment of prion disease in people or livestock remains to be established. PMID:17592554

  19. 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

  20. 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

  1. Dienogest reduces HSD17β1 expression and activity in endometriosis.

    PubMed

    Mori, Taisuke; Ito, Fumitake; Matsushima, Hiroshi; Takaoka, Osamu; Koshiba, Akemi; Tanaka, Yukiko; Kusuki, Izumi; Kitawaki, Jo

    2015-05-01

    Endometriosis is an estrogen-dependent disease. Abnormally biosynthesized estrogens in endometriotic tissues induce the growth of the lesion and worsen endometriosis-associated pelvic pain. Dienogest (DNG), a selective progesterone receptor agonist, is widely used to treat endometriosis and efficiently relieves the symptoms. However, its pharmacological action remains unknown. In this study, we elucidated the effect of DNG on enzymes involved in local estrogen metabolism in endometriosis. Surgically obtained specimens of 23 ovarian endometriomas (OE) and their homologous endometrium (EE), ten OE treated with DNG (OE w/D), and 19 normal endometria without endometriosis (NE) were analyzed. Spheroid cultures of stromal cells (SCs) were treated with DNG and progesterone. The expression of aromatase, 17β-hydroxysteroid dehydrogenase 1 (HSD17β1), HSD17β2, HSD17β7, HSD17β12, steroid sulfatase (STS), and estrogen sulfotransferase (EST) was evaluated by real-time quantitative PCR. The activity and protein level of HSD17β1 were measured with an enzyme assay using radiolabeled estrogens and immunohistochemistry respectively. OESCs showed increased expression of aromatase, HSD17β1, STS, and EST, along with decreased HSD17β2 expression, when compared with stromal cells from normal endometria without endometriosis (NESCs) (P<0.01) or stromal cells from homologous endometrium (EESCs) (P<0.01). In OESCs, DNG inhibited HSD17β1 expression and enzyme activity at 10(-7) M (P<0.01). Results of immunohistochemical analysis displayed reduced HSD17β1 staining intensity in OE w/D (P<0.05). In conclusion, DNG exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and HSD17β1, contributing to a therapeutic effect of DNG on endometriosis. PMID:25767055

  2. Distribution, Activities, and Interactions of Methanogens and Sulfate-Reducing Prokaryotes in the Florida Everglades

    PubMed Central

    Bae, Hee-Sung; Holmes, M. Elizabeth; Chanton, Jeffrey P.; Reddy, K. Ramesh

    2015-01-01

    To gain insight into the mechanisms controlling methanogenic pathways in the Florida Everglades, the distribution and functional activities of methanogens and sulfate-reducing prokaryotes (SRPs) were investigated in soils (0 to 2 or 0 to 4 cm depth) across the well-documented nutrient gradient in the water conservation areas (WCAs) caused by runoff from the adjacent Everglades Agricultural Area. The methyl coenzyme M reductase gene (mcrA) sequences that were retrieved from WCA-2A, an area with relatively high concentrations of SO42− (≥39 μM), indicated that methanogens inhabiting this area were broadly distributed within the orders Methanomicrobiales, Methanosarcinales, Methanocellales, Methanobacteriales, and Methanomassiliicoccales. In more than 3 years of monitoring, quantitative PCR (qPCR) using newly designed group-specific primers revealed that the hydrogenotrophic Methanomicrobiales were more numerous than the Methanosaetaceae obligatory acetotrophs in SO42−-rich areas of WCA-2A, while the Methanosaetaceae were dominant over the Methanomicrobiales in WCA-3A (with relatively low SO42− concentrations; ≤4 μM). qPCR of dsrB sequences also indicated that SRPs are present at greater numbers than methanogens in the WCAs. In an incubation study with WCA-2A soils, addition of MoO42− (a specific inhibitor of SRP activity) resulted in increased methane production rates, lower apparent fractionation factors [αapp; defined as (amount of δ13CO2 + 1,000)/(amount of δ13CH4 + 1,000)], and higher Methanosaetaceae mcrA transcript levels compared to those for the controls without MoO42−. These results indicate that SRPs play crucial roles in controlling methanogenic pathways and in shaping the structures of methanogen assemblages as a function of position along the nutrient gradient. PMID:26276115

  3. Distribution, activities, and interactions of methanogens and sulfate-reducing prokaryotes in the Florida Everglades.

    PubMed

    Bae, Hee-Sung; Holmes, M Elizabeth; Chanton, Jeffrey P; Reddy, K Ramesh; Ogram, Andrew

    2015-11-01

    To gain insight into the mechanisms controlling methanogenic pathways in the Florida Everglades, the distribution and functional activities of methanogens and sulfate-reducing prokaryotes (SRPs) were investigated in soils (0 to 2 or 0 to 4 cm depth) across the well-documented nutrient gradient in the water conservation areas (WCAs) caused by runoff from the adjacent Everglades Agricultural Area. The methyl coenzyme M reductase gene (mcrA) sequences that were retrieved from WCA-2A, an area with relatively high concentrations of SO4 (2-) (≥39 μM), indicated that methanogens inhabiting this area were broadly distributed within the orders Methanomicrobiales, Methanosarcinales, Methanocellales, Methanobacteriales, and Methanomassiliicoccales. In more than 3 years of monitoring, quantitative PCR (qPCR) using newly designed group-specific primers revealed that the hydrogenotrophic Methanomicrobiales were more numerous than the Methanosaetaceae obligatory acetotrophs in SO4 (2-)-rich areas of WCA-2A, while the Methanosaetaceae were dominant over the Methanomicrobiales in WCA-3A (with relatively low SO4 (2-) concentrations; ≤4 μM). qPCR of dsrB sequences also indicated that SRPs are present at greater numbers than methanogens in the WCAs. In an incubation study with WCA-2A soils, addition of MoO4 (2-) (a specific inhibitor of SRP activity) resulted in increased methane production rates, lower apparent fractionation factors [αapp; defined as (amount of δ(13)CO2 + 1,000)/(amount of δ(13)CH4 + 1,000)], and higher Methanosaetaceae mcrA transcript levels compared to those for the controls without MoO4 (2-). These results indicate that SRPs play crucial roles in controlling methanogenic pathways and in shaping the structures of methanogen assemblages as a function of position along the nutrient gradient. PMID:26276115

  4. 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

  5. A method for reducing the level of spurious signals in surface acoustic wave filters

    NASA Astrophysics Data System (ADS)

    Borodii, Iu. N.; Grankin, I. M.; Zapunnyi, A. P.; Kolomeiko, A. V.

    1986-03-01

    A method for reducing spurious signals in surface acoustic wave (SAW) filters is proposed whereby both bulk and reflected wave signals are attenuated by electrodes of special configuration providing synphase addition of the useful signal and nonsynphase addition of spurious signal components. The electrodes of the input and output converters are made with a common focus point and equal angular apertures. The shape of the electrodes of the focusing converters on anisotropic crystal surfaces is determined by the corresponding SAW group velocity curve. An implementation of the method proposed here is examined together with some test results.

  6. Strain-level genomic and physiological variation in four Microbacterium spp.chromate reducers

    EPA Science Inventory

    Hexavalent chromium [Cr(VI)], a soluble carcinogen, has caused widespread contamination of soil and water in many industrial nations. Bacteria have been shown to be an active component in the geochemical cycling of chromium, but the mechanisms governing Cr(VI) reduction are poor...

  7. 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

  8. 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

  9. 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

  10. METHODS FOR CONDUCTING SNAIL (APLEXA HYPNORUM) EMBRYO THROUGH ADULT EXPOSURES: EFFECTS OF CADMIUM AND REDUCED PH LEVELS

    EPA Science Inventory

    Two separate embryo through adult exposures were conducted with cadmium and with reduced pH levels to validate various test methodologies and to determine the feasibility of testing and ease of handling the freshwater snail (Aplexa hypnorum) in a test system designed for fish bio...

  11. Exposure to Organic Solvents Used in Dry Cleaning Reduces Low and High Level Visual Function

    PubMed Central

    Jiménez Barbosa, Ingrid Astrid

    2015-01-01

    Purpose To investigate whether exposure to occupational levels of organic solvents in the dry cleaning industry is associated with neurotoxic symptoms and visual deficits in the perception of basic visual features such as luminance contrast and colour, higher level processing of global motion and form (Experiment 1), and cognitive function as measured in a visual search task (Experiment 2). Methods The Q16 neurotoxic questionnaire, a commonly used measure of neurotoxicity (by the World Health Organization), was administered to assess the neurotoxic status of a group of 33 dry cleaners exposed to occupational levels of organic solvents (OS) and 35 age-matched non dry-cleaners who had never worked in the dry cleaning industry. In Experiment 1, to assess visual function, contrast sensitivity, colour/hue discrimination (Munsell Hue 100 test), global motion and form thresholds were assessed using computerised psychophysical tests. Sensitivity to global motion or form structure was quantified by varying the pattern coherence of global dot motion (GDM) and Glass pattern (oriented dot pairs) respectively (i.e., the percentage of dots/dot pairs that contribute to the perception of global structure). In Experiment 2, a letter visual-search task was used to measure reaction times (as a function of the number of elements: 4, 8, 16, 32, 64 and 100) in both parallel and serial search conditions. Results Dry cleaners exposed to organic solvents had significantly higher scores on the Q16 compared to non dry-cleaners indicating that dry cleaners experienced more neurotoxic symptoms on average. The contrast sensitivity function for dry cleaners was significantly lower at all spatial frequencies relative to non dry-cleaners, which is consistent with previous studies. Poorer colour discrimination performance was also noted in dry cleaners than non dry-cleaners, particularly along the blue/yellow axis. In a new finding, we report that global form and motion thresholds for dry cleaners

  12. Physical Activity Levels in College Students With Chronic Ankle Instability

    PubMed Central

    Hubbard-Turner, Tricia; Turner, Michael J.

    2015-01-01

    Context Ankle sprains are the most common orthopaedic pathologic condition, and more concerning is the high percentage of persons who develop chronic ankle instability (CAI). Researchers have reported that patients with CAI are restricted occupationally, have more functional limitations, and have a poorer health-related quality of life. We do not know if these limitations decrease physical activity levels. Objective To assess total weekly steps taken between persons with CAI and persons with healthy ankles. Design Case-control study. Setting University research laboratory. Patients or Other Participants A total of 20 participants with unilateral CAI (9 men, 11 women; age = 21.2 ± 1.9 years, height = 174.3 ± 6.9 cm, mass = 71.9 ± 11.7 kg) and 20 healthy participants (9 men, 11 women; age = 20.4 ± 2.1 years, height = 172.1 ± 5.5 cm, mass = 73.1 ± 13.4 kg) volunteered. Main Outcome Measure(s) We provided all participants with a pedometer and instructed them to wear it every day for 7 days and to complete a daily step log. They also completed the Foot and Ankle Ability Measure (FAAM), the FAAM Sport version, and the International Physical Activity Questionnaire. A 2-way analysis of variance (group × sex) was used to determine if differences existed in the total number of weekly steps, ankle laxity, and answers on the International Physical Activity Questionnaire between groups and between sexes. Results We found no group × sex interaction for step count (F range = 0.439–2.108, P = .08). A main effect for group was observed (F1,38 = 10.45, P = .04). The CAI group took fewer steps than the healthy group (P = .04). The average daily step count was 6694.47 ± 1603.35 for the CAI group and 8831.01 ± 1290.01 for the healthy group. The CAI group also scored lower on the FAAM (P = .01) and the FAAM Sport version (P = .01). Conclusions The decreased step count that the participants with CAI demonstrated is concerning. This decreased physical activity may be secondary

  13. Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

    PubMed

    McCarty, M F

    1999-12-01

    Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets

  14. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type. PMID:25198797

  15. Regional growth management policies: Toward reducing global warming at state and local levels

    SciTech Connect

    Purdie, J.

    1995-09-01

    State and local governments in the United States are accepting mandates to coordinate legislated land use and growth management planning with vigorous environmental protection and resource conservation. These mandates, implemented or planned in states with populations totaling over 100 million, will directly impact growth patterns and ultimately affect the level of atmospheric gases and particulates generated within their borders. This paper addresses the issues of growth management and land use planning at the local, state and regional levels and identifies areas impacting global warming. A review of existing systems will be presented, and recommendations will be made to improve monitoring of growth management mechanisms and organizational structures with the goal of global atmospheric improvement. The issues discussed include urban sprawl, transportation, and growth patterns as managed by policies also designed to protect environments and provide for sustainable growth. Areas for improved coordination between jurisdictions to ease global warming will also be examined.

  16. The Effect of Gender and Level of Vision on the Physical Activity Level of Children and Adolescents with Visual Impairment

    ERIC Educational Resources Information Center

    Aslan, Ummuhan Bas; Calik, Bilge Basakci; Kitis, Ali

    2012-01-01

    This study was planned in order to determine physical activity levels of visually impaired children and adolescents and to investigate the effect of gender and level of vision on physical activity level in visually impaired children and adolescents. A total of 30 visually impaired children and adolescents (16 low vision and 14 blind) aged between…

  17. Effectiveness of flushing on reducing lead and copper levels in school drinking water.

    PubMed Central

    Murphy, E A

    1993-01-01

    Samples from drinking water fountains in 50 schools in New Jersey were collected at specific times during a typical school day and analyzed for lead, copper, pH, alkalinity, and hardness. First-draw lead and copper levels (medians 0.010 mg/l and 0.26 mg/l, respectively) decreased significantly after 10 min of flushing in the morning (medians 0.005 mg/l lead and 0.068 mg/l copper), but levels increased significantly by lunchtime (medians 0.007 mg/l lead and 0.12 mg/l copper) after normal use of fountains in the morning by students. Corrosive water, as defined by the aggressive index, contained significantly higher levels of lead and copper (medians 0.012 mg/l and 0.605 mg/l, respectively) than noncorrosive water (medians 0.005 mg/l and 0.03 mg/l, respectively). Images p240-a PMID:8404761

  18. by ligand exchange: utilizing energy level alignment for efficiently reducing carrier rec ombination

    NASA Astrophysics Data System (ADS)

    Wang, Xia; Kou, Dong-Xing; Zhou, Wen-Hui; Zhou, Zheng-Ji; Wu, Si-Xin; Cao, Xuan

    2014-05-01

    In this work, we employed a convenient one-step synthesis method for synthesizing Cu2ZnSnSe4 (CZTSe) nanocrystals (NCs) in an excess selenium environment. This excess selenium situation enhanced the reaction of metal acetylacetonates with selenium, resulting in the burst nucleation of NCs at relatively low temperatures. The phase morphology and surface and optoelectronic properties of NCs before and after ligand exchange were discussed in depth. It was found that pure tetragonal-phase structure CZTSe NCs with approximately 1.7-eV bandgap could be synthesized. The removal of large organic molecules on CZTSe NCs after ligand exchange by S2- decreased the resistivity. The bandgap of the films after ligand exchange by 550°C selenization was also decreased due to better crystallinity. For potential application in CZTSe solar cells, we constructed an energy level diagram to explain the mutual effect between the absorption layer and CdS layer. Using cyclic voltammetry (CV) measurement, we found that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of CZTSe films shifted down after ligand exchange. After energy level alignment at the CdS/CZTSe interface, a type I band alignment structure was more conveniently formed after ligand exchange. This structure acted as the barrier against injection electrons from ZnO to the CZTSe layer, and recombination would subsequently be depressed.

  19. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal. PMID:23831729

  20. Optical Mass Gauging System for Measuring Liquid Levels in a Reduced Gravity Environment

    NASA Technical Reports Server (NTRS)

    Sullenberger, Ryan M.; Munoz, Wesley M.; Lyon, Matt P.; Vogel, Kenny; Yalin, Azer P.; Korman, Valentin; Polzin, Kurt A.

    2010-01-01

    A compact and rugged fiber-coupled liquid volume sensor designed for flight on a sounding rocket platform is presented. The sensor consists of a Mach-Zehnder interferometer capable of measuring the amount of liquid contained in a tank under any gravitational conditions, including a microgravity environment, by detecting small changes in the index of refraction of the gas contained within a sensing region. By monitoring changes in the interference fringe pattern as the system undergoes a small compression provided by a piston, the ullage volume of a tank can be directly measured allowing for a determination of the liquid volume. To demonstrate the technique, data are acquired using two tanks containing different volumes of liquid, which are representative of the levels of liquid in a tank at different time periods during a mission. The two tanks are independently exposed to the measurement apparatus, allowing for a determination of the liquid level in each. In a controlled, laboratory test of the unit, the system demonstrated a capability of measuring a liquid level in an individual tank of 10.53 mL with a 2% error. The overall random uncertainty for the flight system is higher than that one test, at +/- 1.5 mL.

  1. Effectiveness of mandated oxygenated fuel usage to reduce carbon monoxide exhaust levels in Colorado

    SciTech Connect

    Cagle, G.A.

    1989-01-01

    An examination of Colorado Automobile Inspection and Readjustment (A.I.R.) two-speed exhaust emissions testing results was undertaken to evaluate changes in carbon monoxide exhaust levels due to the use of oxygenated fuels. Vehicles utilized within the study were separated according to their various emission control technologies: precatalyst (1938 to 1974), catalyst (1975 to 1980), and closed-loop (1981 to 1988). It was found that pre-catalyst and catalyst vehicles utilizing oxygenated fuels had significant reductions in carbon monoxide exhaust levels at 2,500 R.P.M. Results for closed-loop vehicles at 2,500 R.P.M. showed no significant reductions in carbon monoxide exhaust levels. Further examination of idle data for closed-loop vehicles indicated that a small percentage of these vehicles were considered gross-emitters based on the 1.5 percent cut-point set in Colorado. Results of the study indicated that the impact of oxygenated fuels, as well as the rationale for using such fuels as a carbon monoxide reduction strategy, may be difficult to justify as newer, more sophisticated light-duty vehicles comprise a larger proportion of the overall vehicle population in Colorado.

  2. Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease

    PubMed Central

    Khermesh, Khen; D'Erchia, Anna Maria; Barak, Michal; Annese, Anita; Wachtel, Chaim; Levanon, Erez Y.; Picardi, Ernesto; Eisenberg, Eli

    2016-01-01

    Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes ty