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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. Dietary fiber stabilizes blood glucose and insulin levels and reduces physical activity in sows (Sus scrofa).

    PubMed

    de Leeuw, John A; Jongbloed, Age W; Verstegen, Martin W A

    2004-06-01

    The aim of this study was to test whether a diet with a high level of fermentable dietary fiber can stabilize interprandial blood glucose and insulin levels, prevent declines below basal levels, and reduce physical activity in limited-fed breeding sows. Stable levels of glucose and insulin may prevent interprandial feelings of hunger and, consequently, increased activity. Catheterized sows (n = 10) were fed twice daily (0700 and 1900 h) 900 g of a diet with either a low (L-sows) or a high level of fermentable dietary fiber (H-sows; sugarbeet pulp). Blood samples, taken between feeding times, were analyzed for glucose and insulin levels (basal and area under the curve) and stability of levels (variance and sum of absolute differences between levels in consecutive samples). The main focus was on samples taken after the postprandial peak. Behavior was videotaped for analysis of postures and posture changes. Basal glucose and insulin levels did not differ between treatments. H-sows had more stable levels than L-sows. Interprandial levels of H-sows were higher than or equal to basal levels. L-sows showed a decline in glucose below basal levels at 1400 h (P < 0.05). Before 1400 h, no difference in the frequency of posture changes was observed between treatments. After 1400 h, the frequency of posture changes increased more in L-sows than in H-sows. We concluded that sugarbeet pulp as a source of fermentable dietary fiber stabilizes glucose and insulin levels and reduces physical activity in limited-fed sows several hours after feeding. This may indicate a prolonged feeling of satiety.

  3. Instructions, feedback, and reinforcement in reducing activity levels in the classroom.

    PubMed Central

    Schulman, J L; Suran, B G; Stevens, T M; Kupst, M J

    1979-01-01

    The biomotometer, an electronic device which simultaneously measures motor activity and provides auditory feedback, was used in combination with material reinforcers in an experiment to reduce children's activity level in a classroom setting. Subjects were nine boys and two girls, aged 9--13, from a day hospital program for emotionally disturbed children. After five baseline trials, each child had five contingent reinforcement trials in which he/she received feedback "beeps" from the biomotometer and was given toy or candy rewards after each trial in which activity fell at least 20% below mean baseline level. Then five noncontingent reinforcement trials were run in which children received rewards for wearing the apparatus without the feedback attachment. Results indicated that the intervention "package," including instructions, feedback, and contingent reinforcement, was successful in all five trials for 8 of 11 children. Activity levels increased during the final noncontingent phase. PMID:511810

  4. Instructions, feedback, and reinforcement in reducing activity levels in the classroom.

    PubMed

    Schulman, J L; Suran, B G; Stevens, T M; Kupst, M J

    1979-01-01

    The biomotometer, an electronic device which simultaneously measures motor activity and provides auditory feedback, was used in combination with material reinforcers in an experiment to reduce children's activity level in a classroom setting. Subjects were nine boys and two girls, aged 9--13, from a day hospital program for emotionally disturbed children. After five baseline trials, each child had five contingent reinforcement trials in which he/she received feedback "beeps" from the biomotometer and was given toy or candy rewards after each trial in which activity fell at least 20% below mean baseline level. Then five noncontingent reinforcement trials were run in which children received rewards for wearing the apparatus without the feedback attachment. Results indicated that the intervention "package," including instructions, feedback, and contingent reinforcement, was successful in all five trials for 8 of 11 children. Activity levels increased during the final noncontingent phase.

  5. Syzygium cumini inhibits adenosine deaminase activity and reduces glucose levels in hyperglycemic patients.

    PubMed

    Bopp, A; De Bona, K S; Bellé, L P; Moresco, R N; Moretto, M B

    2009-08-01

    Syzigium cumini (L.) Skeels from the Myrtaceae family is among the most common medicinal plants used to treat diabetes in Brazil. Leaves, fruits, and barks of S. cumini have been used for their hypoglycemic activity. Adenosine deaminase (ADA) is an important enzyme that plays a relevant role in purine and DNA metabolism, immune responses, and peptidase activity. ADA is suggested to be an important enzyme for modulating the bioactivity of insulin, but its clinical significance in diabetes mellitus (DM) has not yet been proven. In this study, we examined the effect of aqueous leaf extracts of S. cumini (L.) (ASC) on ADA activity of hyperglycemic subjects and the activity of total ADA, and its isoenzymes in serum and erythrocytes. The present study indicates that: (i) the ADA activity in hyperglycemic serum was higher than normoglycemic serum and ADA activity was higher when the blood glucose level was more elevated; (ii) ASC (60-1000 microg/mL) in vitro caused a concentration-dependent inhibition of total ADA activity and a decrease in the blood glucose level in serum; (iii) ADA1 and 2 were reduced both in erythrocytes and in hyperglycemic serum. These results suggest that the decrease of ADA activity provoked by ASC may contribute to control adenosine levels and the antioxidant defense system of red cells and could be related to the complex ADA/DPP-IV-CD26 and the properties of dipeptidyl peptidase IV (DPP-IV) inhibitors which serve as important regulators of blood glucose.

  6. Enterolactone Reduces Telomerase Activity and The Level of Its Catalytic Subunit in Breast Cancer Cells.

    PubMed

    Ilbeigi, Davod; Nourbakhsh, Mitra; Khaghani, Shahnaz; Einollahi, Nahid; Kheiripour, Nejat; Gholinejad, Zafar; Alaee, Mohammad; Saberian, Mostafa

    2017-01-01

    There is a positive correlation between higher serum phytoestrogen concentrations and lower risk of breast cancer. The activation of telomerase is crucial for the growth of cancer cells; therefore, the aim of this study was to examine the effects of enterolactone (ENL) and enterodiol (END) on this enzyme. In this experimental study, we performed the viability assay to determine the effects of different concentrations of ENL and END on cell viability, and the effective concentrations of these two compounds on cell growth. We used western blot analysis to evaluate human telomerase reverse transcriptase catalytic subunit (hTERT) expression and polymerase chain reaction (PCR)-ELISA based on the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Both ENL and END, at 100 μM concentrations, significantly (P<0.05) reduced cell viability. However, only the 100 μM concentration of ENL significantly (P<0.05) decreased hTERT protein levels and telomerase activity. Lower concentrations of ENL did not have any significant effects on telomerase activity and hTERT protein levels. High concentration of ENL decreased the viability of MCF-7 breast cancer cells and inhibited the expression and activity of telomerase in these cells. Although END could reduce breast cancer cell viability, it did not have any effect on telomerase expression and activity.

  7. Enterolactone Reduces Telomerase Activity and The Level of Its Catalytic Subunit in Breast Cancer Cells

    PubMed Central

    Ilbeigi, Davod; Nourbakhsh, Mitra; Khaghani, Shahnaz; Einollahi, Nahid; Kheiripour, Nejat; Gholinejad, Zafar; Alaee, Mohammad; Saberian, Mostafa

    2017-01-01

    Objective There is a positive correlation between higher serum phytoestrogen concentrations and lower risk of breast cancer. The activation of telomerase is crucial for the growth of cancer cells; therefore, the aim of this study was to examine the effects of enterolactone (ENL) and enterodiol (END) on this enzyme. Materials and Methods In this experimental study, we performed the viability assay to determine the effects of different concentrations of ENL and END on cell viability, and the effective concentrations of these two compounds on cell growth. We used western blot analysis to evaluate human telomerase reverse transcriptase catalytic subunit (hTERT) expression and polymerase chain reaction (PCR)-ELISA based on the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Results Both ENL and END, at 100 μM concentrations, significantly (P<0.05) reduced cell viability. However, only the 100 μM concentration of ENL significantly (P<0.05) decreased hTERT protein levels and telomerase activity. Lower concentrations of ENL did not have any significant effects on telomerase activity and hTERT protein levels. Conclusion High concentration of ENL decreased the viability of MCF-7 breast cancer cells and inhibited the expression and activity of telomerase in these cells. Although END could reduce breast cancer cell viability, it did not have any effect on telomerase expression and activity. PMID:28580306

  8. Reduced Activity-Dependent Protein Levels in a Mouse Model of the Fragile X Premutation

    PubMed Central

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

    2014-01-01

    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

  9. 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.

  10. 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

  11. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

    PubMed

    Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N'Faly; Gabriel, Martin; Günther, Stephan; Oestereich, Lisa; Muñoz-Fontela, César

    2016-10-15

    A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16(+) monocytes with a poor activation profile. In survivors, CD16(+) monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    PubMed

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

    2015-09-09

    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.

  13. 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

  14. Reduced Levels of Hspa9 Attenuates Stat5 Activation in Mouse B-cells

    PubMed Central

    Krysiak, Kilannin; Tibbitts, Justin F.; Shao, Jin; Liu, Tuoen; Ndonwi, Matthew; Walter, Matthew J.

    2014-01-01

    HSPA9 is located on chromosome 5q31.2 in humans, a region that is commonly deleted in patients with myeloid malignancies [del(5q)], including myelodysplastic syndromes (MDS). HSPA9 expression is reduced by 50% in patients with del(5q)-associated MDS, consistent with haploinsufficient levels. Zebrafish mutants and knockdown studies in human and mouse cells have implicated a role for HSPA9 in hematopoiesis. To comprehensively evaluate the effects of Hspa9 haploinsufficiency on hematopoiesis, we generated an Hspa9 knockout mouse model. While homozygous knockout of Hspa9 is embryonic lethal, mice with heterozygous deletion of Hspa9 (Hspa9+/−) are viable and have a 50% reduction in Hspa9 expression. Hspa9+/− mice have normal basal hematopoiesis and do not develop MDS. However, Hspa9+/− mice have a cell- intrinsic reduction in bone marrow CFU-PreB colony formation without alterations in the number of B-cell progenitors in vivo, consistent with a functional defect in Hspa9+/− B-cell progenitors. We further reduced Hspa9 expression (<50%) using RNAi and observe reduced B-cell progenitors in vivo, indicating that appropriate levels (≥50%) of Hspa9 are required for normal B- lymphopoiesis in vivo. Knockdown of Hspa9 in an IL-7 dependent mouse B-cell line reduced Stat5 phosphorylation following IL-7 receptor stimulation, supporting a role for Hspa9 in Stat5 signaling in B-cells. Collectively, these data implicate a role for Hspa9 in B-lymphopoiesis and Stat5 activation downstream of IL-7 signaling. PMID:25550197

  15. Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome.

    PubMed

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

    2016-02-15

    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. © The Author 2015. Published by Oxford University Press.

  16. Instructions, Feedback, and Reinforcement in Reducing Activity Levels in the Classroom.

    ERIC Educational Resources Information Center

    Schulman, Jerome L.; And Others

    1979-01-01

    Results indicated that the intervention package--including instructions, feedback from an electronic device that measures motor activity, and contingent reinforcement--was successful in reducing activity in the classroom for 8 of the 11 emotionally disturbed Ss (ages 9 to 13 years). (Author/DLS)

  17. Activity wheel running reduces escape latency and alters brain monoamine levels after footshock.

    PubMed

    Dishman, R K; Renner, K J; Youngstedt, S D; Reigle, T G; Bunnell, B N; Burke, K A; Yoo, H S; Mougey, E H; Meyerhoff, J L

    1997-01-01

    We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (approximately 50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9-12 weeks, animals were matched in pairs on body mass. Activity wheel animals were also matched on running distance. An animal from each matched pair was randomly assigned to controllable or uncontrollable inescapable foot shock followed the next day by a foot shock escape test in a shuttle box. Brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in the locus coeruleus (LC), dorsal raphe (DR), central amygdala (AC), hippocampus (CA1), arcuate nucleus, paraventricular nucleus (PVN), and midbrain central gray. After prior exposure to uncontrollable foot shock, escape latency was reduced by 34% for wheel runners compared with sedentary controls. The shortened escape latency for wheel runners was associated with 61% higher NE concentrations in LC and 44% higher NE concentrations in DR compared with sedentary controls. Sedentary controls, compared with wheel runners, had 31% higher 5-HIAA concentrations in CA1 and 30% higher 5-HIAA concentrations in AC after uncontrollable foot shock and had 28% higher 5-HT and 33% higher 5-HIAA concentrations in AC averaged across both foot shock conditions. There were no group differences in monoamines in the central gray or in plasma prolactin or ACTH concentrations, despite 52% higher DA concentrations in the arcuate nucleus after uncontrollable foot shock and 50% higher DOPAC/DA and 17% higher 5-HIAA/5-HT concentrations in the PVN averaged across both foot shock conditions for sedentary compared with activity wheel animals. The present results extend understanding of the

  18. 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

  19. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels.

    PubMed

    Slyker, Jennifer A; Richardson, Barbra; Chung, Michael H; Atkinson, Claire; Ásbjörnsdóttir, Kristjana H; Lehman, Dara A; Boeckh, Michael; Emery, Vincent; Kiarie, James; John-Stewart, Grace

    2017-04-01

    To evaluate the impact of highly active antiretroviral therapy (HAART) on CMV transmission and breast milk level in the context of maternal HIV. Specimens from a randomized trial conducted in Nairobi, Kenya between 2003-2005 were used to compare CMV transmission and breast milk levels between mother-infant pairs randomized to HAART versus short-course antenatal zidovudine plus single-dose nevirapine (ZDV/sdNVP) for prevention of mother-to-child HIV transmission (PMTCT). Fifty-one antiretroviral-naïve women ≤32 weeks gestation, and CD4 between 200-500 cells/mm(3) were randomized at 34 weeks to begin either antenatal ZDV/sdNVP, or HAART through 6 months postpartum. Mean breast milk CMV levels and transmission were compared between arms. Age, sociodemographics, CD4%, and HIV plasma RNA viral load were similar between arms at baseline. CMV viral loads were measured from 243 infant plasma and 185 breast milk specimens during the first year postpartum. The probability of infant CMV infection at 12 months was 19% lower in the HAART arm compared to ZDV/sdNVP (75% vs. 94%, p = .04). All women had CMV detected in breast milk, with 72%, 98%, and 97% testing positive during the first, second, and third weeks postpartum, respectively. There was a trend for early higher mean breast milk CMV level in the HAART arm at 1 week (p = .08), and there was significantly slower decline in breast milk CMV levels (area under the curve, p = .01). HAART started during the third trimester may decrease infant CMV infections, by mechanisms independent of breast milk CMV levels.

  20. Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.

    PubMed

    Rocha, Natalia Pessoa; Assis, Frankcinéia; Scalzo, Paula Luciana; Vieira, Érica Leandro Marciano; Barbosa, Izabela Guimarães; de Souza, Mariana Soares; Christo, Paulo Pereira; Reis, Helton José; Teixeira, Antonio Lucio

    2017-02-07

    Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

  1. Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.

    PubMed

    Briffa, Jessica F; Grinfeld, Esther; McAinch, Andrew J; Poronnik, Philip; Hryciw, Deanne H

    2014-01-25

    Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and 0.50 μg/ml) significantly reduced the metabolic activity of PTCs, and significantly decreased protein content per cell. Investigation of the role of p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that the mTOR pathway is responsible for the reduction in PTC metabolic activity in response to leptin. However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway.

  2. 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.

  3. Early life undernutrition alters the level of reduced glutathione but not the activity levels of reactive oxygen species enzymes or lipid peroxidation in the mouse forebrain.

    PubMed

    Partadiredja, G; Worrall, S; Bedi, K S

    2009-08-18

    Diet restriction of rodents during adult life is known to cause an increased life span. It has been hypothesised that this increase may be related to effects on the anti-oxidant defence systems. However, it has been suggested that undernutrition during the gestation and pre-weaning may reduce their life span as it is known to have other deleterious effects on a rodent's growth and development. We have now examined the activity levels of some anti-oxidant defence system enzymes and other markers of oxidative stress in mice that have been undernourished from conception until 21 postnatal days of age, followed in some cases by a period of nutritional rehabilitation until 61 days of age. We found that such undernutrition exerted only minimal effects on oxidative stress markers under investigation (ROS enzyme activities, GSH levels, and lipid peroxidation). Only GSH levels were significantly affected by pre-weaning undernutrition. In conclusion, pre-weaning undernutrition may regulate anti-oxidant enzymes at the transcriptional level differently from that at the post-transcriptional, translational, or post-translational levels. The possible effects that these changes at the cellular level, may have on the longevity of the animals remain of great interest and importance.

  4. RNA interference (RNAi)-induced suppression of nicotine demethylase activity reduces levels of a key carcinogen in cured tobacco leaves.

    PubMed

    Lewis, Ramsey S; Jack, Anne M; Morris, Jerry W; Robert, Vincent J M; Gavilano, Lily B; Siminszky, Balazs; Bush, Lowell P; Hayes, Alec J; Dewey, Ralph E

    2008-05-01

    Technologies for reducing the levels of tobacco product constituents that may contribute to unwanted health effects are desired. Target compounds include tobacco-specific nitrosamines (TSNAs), a class of compounds generated through the nitrosation of pyridine alkaloids during the curing and processing of tobacco. Studies have reported the TSNA N'-nitrosonornicotine (NNN) to be carcinogenic in laboratory animals. NNN is formed via the nitrosation of nornicotine, a secondary alkaloid produced through enzymatic N-demethylation of nicotine. Strategies to lower nornicotine levels in tobacco (Nicotiana tabacum L.) could lead to a corresponding decrease in NNN accumulation in cured leaves. The major nicotine demethylase gene of tobacco has recently been isolated. In this study, a large-scale field trial was conducted to evaluate transgenic lines of burley tobacco carrying an RNA interference (RNAi) construct designed to inhibit the expression of this gene. Selected transgenic lines exhibited a six-fold decrease in nornicotine content relative to untransformed controls. Analysis of cured leaves revealed a commensurate decrease in NNN and total TSNAs. The inhibition of nicotine demethylase activity is an effective means of decreasing significantly the level of a key defined animal carcinogen present in tobacco products.

  5. The butanol fraction of Eclipta prostrata (Linn) effectively reduces serum lipid levels and improves antioxidant activities in CD rats.

    PubMed

    Kim, Dae-Ik; Lee, Sung-Hyen; Choi, Jin-Ho; Lillehoj, Hyun Soon; Yu, Mi-Hee; Lee, Gun-Soon

    2008-08-01

    Eclipta prostrata (Linn) has been used as a traditional medicinal plant to prevent lipidemia and atherosclerosis in Asia. However, its functional properties and the underlying mechanism of action have not been clearly defined. This study was conducted to elucidate the biological basis for hypolipidemic and antioxidant activities of E. prostrata. Charles River Sprague-Dawley CD rats (specific pathogen-free/viral antibody-free Crj/Bgi male, 180 +/- 10 g) were fed experimental diets supplemented with 0 mg (control), 25 mg (E25), 50 mg (E50), or 100 mg (E100) of a freeze-dried butanol fraction of E. prostrata per kilogram of diet for 6 weeks. Serum triacylglycerol and total cholesterol levels were significantly lower in the E50 and E100 groups by 9.8% to 19.0% and by 10.7% to 13.4%, respectively, and low-density lipoprotein-cholesterol levels were significantly reduced in the same groups by 10.3% to 13.0% compared with the untreated control group. The E50 and E100 groups also showed significantly increased high-density lipoprotein-cholesterol levels (13.0%-19.1%) compared with the control group. Atherogenic indices were decreased by 9.8% to 30.5% in all groups fed diets supplemented with E. prostrata. Furthermore, serum hydroxyl radical, lipid peroxide, and oxidized protein levels were significantly decreased in the E50 and E100 groups. These results clearly demonstrate the effects of E. prostrata on serum lipid and oxidative metabolism in rats. The health-promoting effects of E. prostrata, which were demonstrated in this study in a rat model, may have implications for atherosclerosis and hypercholesterolemia in humans.

  6. 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

  7. Sunscreen protection against ultraviolet-induced oxidative stress: evaluation of reduced glutathione levels, metalloproteinase secretion, and myeloperoxidase activity.

    PubMed

    Vilela, F M P; Fonseca, Y M; Vicentini, F T M C; Fonseca, M J V

    2013-11-01

    Several studies have demonstrated the skin protection by sunscreens considering the aspects skin penetration, photostability, and protection against erythema and sunburn. However, little is known about the effect of topically applied sunscreen formulations on the antioxidant defense, metalloproteinases, and inflammatory processes of skin in response to UVR exposure. Therefore, this study aimed to investigate the use of a cream gel formulation containing the UV filters benzophenone-3, octyl methoxycinnamate, and octyl salicylate to prevent skin damage from a single dose of UVR (2.87 J/cm2). This protective effect was evaluated in vivo by measuring the following biochemical parameters: reduced glutathione levels, secretion of matrix metalloproteinases, and myeloperoxidase activity. The results showed that the sunscreen formulation, despite having sun protection factor (SPF) 15, was not completely effective to protect the skin against GSH depletion, MMP-9 secretion and the inflammatory process induced by UVR. These results demonstrate the importance of analyzing UV-altered biochemical parameters of skin in order to propose new sunscreen formulations that can completely protect skin against UVR-induced damage.

  8. Central alpha-activation by clonidine reduces plasma level of beta-endorphin in patients with essential hypertension.

    PubMed

    Yasunari, K; Kanayama, Y; Kohno, M; Murakawa, K; Kawarabayashi, T; Takeda, T; Kotsugai, N; Sato, K

    1985-10-21

    Whether peripheral beta-endorphin contributes to the antihypertensive action of clonidine was examined by measuring plasma levels of beta-endorphin-like immunoreactivity (beta EpLI) after acute administration of clonidine in patients with essential hypertension. Administration of clonidine (0.225 mg) in one dose significantly lowered blood pressure, decreased heart rate and reduced the plasma level of beta EpLI and ACTH, while the placebo had no effect on blood pressure, heart rate or plasma level of beta EpLI suggesting that peripheral beta-endorphin does not play a major role in the antihypertensive action of acute clonidine administration.

  9. 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

  10. Chronic alcohol binging injures the liver and other organs by reducing NAD⁺ levels required for sirtuin's deacetylase activity.

    PubMed

    French, Samuel W

    2016-04-01

    NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de-acetylate acetylated proteins such as acetylated histones. This prevents the epigenetic changes that regulate metabolic processes and which prevent organ injury such as fatty liver in response to alcohol abuse. Hyper acetylation of numerous regulatory proteins develops. Systemic multi-organ injury occurs when NAD(+) is reduced. For instance the Circadian clock is altered if NAD(+) is not available. Cell cycle arrest occurs due to up regulation of cell cycle inhibitors leading to DNA damage, mutations, apoptosis and tumorigenesis. NAD(+) is linked to aging in the regulation of telomere stability. NAD(+) is required for mitochondrial renewal. Alcohol dehydrogenase is present in every visceral organ in the body so that there is a systemic reduction of NAD(+) levels in all of these organs during binge drinking.

  11. 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

  12. 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.

  13. Reduced complexity of force and muscle activity during low level isometric contractions of the ankle in diabetic individuals.

    PubMed

    Suda, E Y; Madeleine, P; Hirata, R P; Samani, A; Kawamura, T T; Sacco, I C N

    2017-02-01

    This study evaluated the structure and amount of variability of surface electromyography (sEMG) patterns and ankle force data during low-level isometric contractions in diabetic subjects with different degrees of neuropathy. We assessed 10 control subjects and 38 diabetic patients, classified as absent, mild, moderate, or severe neuropathy, by a fuzzy system based on clinical variables. Multichannel sEMG (64-electrode matrix) of tibialis anterior and gastrocnemius medialis muscles were acquired during isometric contractions at 10%, 20%, and 30% of the maximum voluntary contraction, and force levels during dorsi- and plantarflexion were recorded. Standard deviation and sample entropy of force signals were calculated and root mean square and sample entropy were calculated from sEMG signals. Differences among groups of force and sEMG variables were verified using a multivariate analysis of variance. Overall, during dorsiflexion contractions, moderate and severe subjects had higher force standard deviation and moderate subjects had lower force sample entropy. During plantarflexion, moderate subjects had higher force standard deviation and all diabetic subjects had lower entropy. Tibialis anterior presented higher root mean square in absent group and lower entropy in mild subjects. For gastrocnemius medialis, entropy was higher in severe and lower in moderate subjects. Diabetic neuropathy affects the complexity of the neuromuscular system during low-level isometric contractions, reducing the system's capacity to adapt to challenging mechanical demands. The observed patterns of neuromuscular complexity were not associated with disease severity, with the majority of alterations recorded in moderate subject. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. VS411 Reduced Immune Activation and HIV-1 RNA Levels in 28 Days: Randomized Proof-of-Concept Study for AntiViral-HyperActivation Limiting Therapeutics

    PubMed Central

    Lori, Franco; De Forni, Davide; Katabira, Elly; Baev, Denis; Maserati, Renato; Calarota, Sandra A.; Cahn, Pedro; Testori, Marco; Rakhmanova, Aza; Stevens, Michael R.

    2012-01-01

    Background A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4+ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects. Methods Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests. Results VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4+ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: −1.47 log10 copies/mL; CD4+ T cell count: +135 cells/mm3) and fewest adverse events. Conclusions VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system

  15. Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water

    PubMed Central

    Hamasaki, Takeki; Harada, Gakuro; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro; Fugetsu, Bunshi; Gong, Wei; Sakata, Ichiro; Shirahata, Sanetaka

    2017-01-01

    Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles. PMID:28182635

  16. Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water.

    PubMed

    Hamasaki, Takeki; Harada, Gakuro; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro; Fugetsu, Bunshi; Gong, Wei; Sakata, Ichiro; Shirahata, Sanetaka

    2017-01-01

    Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles.

  17. Higher Levels and Intensity of Physical Activity Are Associated with Reduced Mortality among Community Dwelling Older People

    PubMed Central

    Hrobonova, Eva; Breeze, Elizabeth; Fletcher, Astrid E.

    2011-01-01

    Introduction. There is limited evidence on physical activity and mortality in older people. Methods. People aged 75–84 years (n = 1449) participating in a randomized trial of health screening in UK general practice were interviewed about their physical activity (PA) and were assessed for a wide range of health and social problems. Mortality data were collected over 7 years of followup. Results. Full information on PA and potential confounders was available in 946 people. Those in the highest third of duration of PA had a lower mortality, confounder-adjusted Hazard Ratio (HR) = 0.74, and 95% Confidence Interval (CI) 0.56–0.97, compared to the lowest third. Similar benefits were seen when categorized by intensity of PA, with those in the highest group having a lower mortality, confounder-adjusted HR = 0.61, and 95% CI 0.47–0.79, compared to the lowest category. Conclusions. Our results suggest the importance of providing older people with opportunities for physical activity. PMID:21437004

  18. n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels

    PubMed Central

    Fakhrudin, Nanang; Dwi Astuti, Eny; Sulistyawati, Rini; Santosa, Djoko; Susandarini, Ratna; Nurrochmad, Arief; Wahyuono, Subagus

    2017-01-01

    Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1). PMID:28335408

  19. n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels.

    PubMed

    Fakhrudin, Nanang; Dwi Astuti, Eny; Sulistyawati, Rini; Santosa, Djoko; Susandarini, Ratna; Nurrochmad, Arief; Wahyuono, Subagus

    2017-03-13

    Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).

  20. 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

  1. Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduceslevel and microglia activation in the brains of 3xTg-AD mice.

    PubMed

    Chen, Yanxing; Zhao, Yang; Dai, Chun-Ling; Liang, Zhihou; Run, Xiaoqin; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2014-11-01

    Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced Aβ40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD.

  2. An enriched environment reduces the stress level and locomotor activity induced by acute morphine treatment and by saline after chronic morphine treatment in mice.

    PubMed

    Xu, Jia; Sun, Jinling; Xue, Zhaoxia; Li, Xinwang

    2014-06-18

    This study investigated the relationships among an enriched environment, stress levels, and drug addiction. Mice were divided randomly into four treatment groups (n=12 each): enriched environment without restraint stress (EN), standard environment without restraint stress (SN), enriched environment with restraint stress (ES), and standard environment with restraint stress (SS). Mice were reared in the respective environment for 45 days. Then, the ES and SS groups were subjected to restraint stress daily (2 h/day) for 14 days, whereas the EN and SN groups were not subjected to restraint stress during this stage. The stress levels of all mice were tested in the elevated plus maze immediately after exposure to restraint stress. After the 2-week stress testing period, mice were administered acute or chronic morphine (5 mg/kg) treatment for 7 days. Then, after a 7-day withdrawal period, the mice were injected with saline (1 ml/kg) or morphine (5 mg/kg) daily for 2 days to observe locomotor activity. The results indicated that the enriched environment reduced the stress and locomotor activity induced by acute morphine administration or saline after chronic morphine treatment. However, the enriched environment did not significantly inhibit locomotor activity induced by morphine challenge. In addition, the stress level did not mediate the effect of the enriched environment on drug-induced locomotor activity after acute or chronic morphine treatment.

  3. Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema.

    PubMed

    Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

    2016-12-13

    BACKGROUND Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). MATERIAL AND METHODS TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. RESULTS We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (p<0.05 and p<0.001, respectively) and decreased the cortical lesion volume (p<0.05 and p<0.001, respectively) compared with vehicle-only treatment. PA treatment at the dose of 125 mg/kg attenuated brain edema and ameliorated BBB integrity. In addition, PA treatment significantly reduced the loss of ATP (p<0.01), reduced lactic acid levels (p<0.001), and increased the activity of Na+/K+-ATPase (p<0.01). CONCLUSIONS Our results indicate PA has neuroprotective effects on TBI through increasing ATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA.

  4. Potassium Aspartate Attenuates Brain Injury Induced by Controlled Cortical Impact in Rats Through Increasing Adenosine Triphosphate (ATP) Levels, Na+/K+-ATPase Activity and Reducing Brain Edema

    PubMed Central

    Gu, Yi; Zhang, Jie; Zhao, Yumei; Su, Yujin; Zhang, Yazhuo

    2016-01-01

    Background Potassium aspartate (PA), as an electrolyte supplement, is widely used in clinical practice. In our previous study, we found PA had neuroprotective effects against apoptosis after cerebral ischemia/reperfusion in rats. In this study, we examine whether PA has protective effects on traumatic brain injury (TBI). Material/Methods TBI was induced by controlled cortical impact (CCI) in rats. Vehicle treatment (control) or PA treatment was administered intraperitoneally at 30 minutes after CCI. The modified neurological severity score (mNSS) and cortical lesion volume were examined. Brain edema and blood-brain barrier (BBB) integrity were measured, as well as brain ATP contents, lactic acid levels, and Na+/K+-ATPase activities. Results We found that CCI induced cortical injury in rats. Acute PA treatment at the dose of 62.5 mg/kg and 125 mg/kg significantly improved neurological deficits (p<0.05 and p<0.001, respectively) and decreased the cortical lesion volume (p<0.05 and p<0.001, respectively) compared with vehicle-only treatment. PA treatment at the dose of 125 mg/kg attenuated brain edema and ameliorated BBB integrity. In addition, PA treatment significantly reduced the loss of ATP (p<0.01), reduced lactic acid levels (p<0.001), and increased the activity of Na+/K+-ATPase (p<0.01). Conclusions Our results indicate PA has neuroprotective effects on TBI through increasing ATP levels, Na+/K+-ATPase activity, and reducing brain edema. It provides experimental evidence for the clinical application of PA. PMID:27959885

  5. 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

  6. 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

    2016-09-02

    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

  7. Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection.

    PubMed

    de Gottardi, A; Pazienza, V; Pugnale, P; Bruttin, F; Rubbia-Brandt, L; Juge-Aubry, C E; Meier, C A; Hadengue, A; Negro, F

    2006-01-01

    Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. PPAR-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b. The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.

  8. Physical activity in overweight and obese pregnant women is associated with higher levels of proinflammatory cytokines and with reduced insulin response through interleukin-6.

    PubMed

    van Poppel, Mireille N M; Peinhaupt, Miriam; Eekhoff, Marelise E W; Heinemann, Akos; Oostdam, Nicolette; Wouters, Maurice G A J; van Mechelen, Willem; Desoye, Gernot

    2014-04-01

    OBJECTIVE Previously, we reported the positive association of moderate-to-vigorous physical activity (MVPA) with insulin sensitivity in overweight and obese pregnant women. We sought to assess whether these MVPA-induced changes in insulin sensitivity are mediated by changes in interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and IL-1β. RESEARCH DESIGN AND METHODS A prospective longitudinal study was conducted in 46 overweight and obese women at risk for gestational diabetes mellitus. Objective physical activity measurements and fasting blood samples were taken at 15, 24, and 32 weeks of pregnancy. At 24 and 32 weeks, a 100-g oral glucose test was performed in addition. Cytokines, C-reactive protein, and glucose and insulin levels were measured, and insulin sensitivity and first-phase insulin response were calculated. Relationships between the different parameters were assessed using linear regression models, adjusting for maternal age and BMI. RESULTS All cytokines were elevated in women with higher levels of MVPA at 15 weeks of gestation. Higher IL-6 was related to a lower first-phase insulin response (β -810.5 [95% CI -1,524.5 to -96.5]; P = 0.03). TNF-α and IL-1β had different effects in women with low MVPA (with low IL-6 levels) compared with more active women. CRP was not related to MVPA. CONCLUSIONS The association of MVPA with insulin sensitivity and first-phase insulin response may be (partly) mediated by IL-6, since this cytokine was related to reduced first-phase insulin response. The possible positive effects of the elevated cytokine profile in active obese pregnant women warrant further study.

  9. 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

  10. Continuous delta opioid receptor activation reduces neuronal voltage gated sodium channel (NaV1.7) levels through activation of protein kinase C in painful diabetic neuropathy

    PubMed Central

    Chattopadhyay, Munmun; Mata, Marina; Fink, David J.

    2012-01-01

    The NaV1.7 tetrodotoxin-sensitive voltage-gated sodium channel isoform plays a critical role in nociception. In rodent models of diabetic neuropathy, increased NaV1.7 in dorsal root ganglion (DRG) neurons correlates with the emergence of pain-related behaviors characteristic of painful diabetic neuropathy (PDN). We examined the effect of transgene-mediated expression of enkephalin on pain-related behaviors and their biochemical correlates in DRG neurons. Transfection of DRG neurons by subcutaneous inoculation of a herpes simplex virus (HSV)-based vector expressing proenkephalin (PE) reversed nocisponsive behavioral responses to heat, cold, and mechanical pressure characteristic of PDN. Vector-mediated enkephalin production in vivo prevented the increase in DRG NaV1.7 observed in PDN, an effect that correlated with inhibition of phosphorylation of p38 MAP kinase and protein kinase C (PKC). Primary DRG neurons in vitro exposed to 45 mM glucose for 18 hrs also demonstrated an increase in NaV1.7 and increased phosphorylation of p38 and PKC; these changes were prevented by transfection in vitro with the enkephalin-expressing vector. The effect of hyperglycemia on NaV1.7 production in vitro was mimicked by exposure to PMA, and blocked by the myristolated PKC inhibitor 20–28 or the p38 inhibitor SB202190; the effect of vector-mediated enkephalin on NaV1.7 levels was prevented by naltrindole. The results of these studies suggest that activation of the presynaptic delta opioid receptor by enkephalin prevents the increase in neuronal NaV1.7 in DRG through inhibition of PKC and p38. These results establish a novel interaction between the delta opioid receptor and voltage gated sodium channels. PMID:18579738

  11. Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer's disease patients

    PubMed Central

    Kato, Tomoko; Konishi, Yoshihiro; Shimohama, Shun; Beach, Thomas G.; Akatsu, Hiroyasu; Tooyama, Ikuo

    2015-01-01

    Alpha1-chimaerin is a GTPase-activating protein (GAP) for Rac1, a member of the Rho small GTPase family, whose action leads to the inactivation of Rac1. Rac1 activity is upregulated in Alzheimer's disease, but little is known about the role of α1-chimaerin. In this study, we investigated the expression and localization of α1-chimaerin mRNA in postmortem human brains from patients with Alzheimer's disease and control subjects. In situ hybridization studies demonstrated that α1-chimaerin was expressed by neurons in the neo-cortex of the temporal lobe and the hippocampus of both controls and Alzheimer's disease cases, with the signal intensity dramatically decreased in patients with Alzheimer's disease. Real-time PCR analysis confirmed a significant reduction of α1-chimaerin mRNA expression in the temporal cortex of Alzheimer's disease cases. In contrast, α2-chimaerin mRNA levels showed no significant difference between the groups. The present study showed reduced α1-chimaerin expression in the brain of Alzheimer's disease cases, suggesting a role in the upregulation of Rac1 activity during the disease process. PMID:25676811

  12. Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities of nitrogen-uptake and -assimilatory proteins in tomato roots.

    PubMed

    Jayawardena, Dileepa M; Heckathorn, Scott A; Bista, Deepesh R; Mishra, Sasmita; Boldt, Jennifer K; Krause, Charles R

    2017-03-01

    Atmospheric CO2 enrichment is expected to often benefit plant growth, despite causing global warming and nitrogen (N) dilution in plants. Most plants primarily procure N as inorganic nitrate (NO3(-) ) or ammonium (NH4(+) ), using membrane-localized transport proteins in roots, which are key targets for improving N use. Although interactive effects of elevated CO2 , chronic warming and N form on N relations are expected, these have not been studied. In this study, tomato (Solanum lycopersicum) plants were grown at two levels of CO2 (400 or 700 ppm) and two temperature regimes (30 or 37°C), with NO3(-) or NH4(+) as the N source. Elevated CO2 plus chronic warming severely inhibited plant growth, regardless of N form, while individually they had smaller effects on growth. Although %N in roots was similar among all treatments, elevated CO2 plus warming decreased (1) N-uptake rate by roots, (2) total protein concentration in roots, indicating an inhibition of N assimilation and (3) shoot %N, indicating a potential inhibition of N translocation from roots to shoots. Under elevated CO2 plus warming, reduced NO3(-) -uptake rate per g root was correlated with a decrease in the concentration of NO3(-) -uptake proteins per g root, reduced NH4(+) uptake was correlated with decreased activity of NH4(+) -uptake proteins and reduced N assimilation was correlated with decreased concentration of N-assimilatory proteins. These results indicate that elevated CO2 and chronic warming can act synergistically to decrease plant N uptake and assimilation; hence, future global warming may decrease both plant growth and food quality (%N). © 2016 Scandinavian Plant Physiology Society.

  13. VS411 reduced immune activation and HIV-1 RNA levels in 28 days: randomized proof-of-concept study for antiviral-hyperactivation limiting therapeutics.

    PubMed

    Lori, Franco; De Forni, Davide; Katabira, Elly; Baev, Denis; Maserati, Renato; Calarota, Sandra A; Cahn, Pedro; Testori, Marco; Rakhmanova, Aza; Stevens, Michael R

    2012-01-01

    A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4(+) T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects. Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests. VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4(+) T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: -1.47 log(10) copies/mL; CD4(+) T cell count: +135 cells/mm(3)) and fewest adverse events. VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system activation associated with HIV

  14. Ornithine phenylacetate targets alterations in the expression and activity of glutamine synthase and glutaminase to reduce ammonia levels in bile duct ligated rats.

    PubMed

    Jover-Cobos, M; Noiret, L; Lee, K; Sharma, V; Habtesion, A; Romero-Gomez, M; Davies, N; Jalan, R

    2014-03-01

    In liver failure, ammonia homeostasis is dependent upon the function of the ammonia metabolising enzymes, glutamine synthetase (GS) and glutaminase (GA) but data about their protein expression and activity are lacking. The aims of this study were to determine the protein expression and activity of GS and GA in individual organs in a rat model of chronic liver disease and to test whether the treatment with the ammonia-lowering agent ornithine phenylacetate (OP) modulates their activities. 49 SD rats were studied 35 days after sham-operation or bile duct ligation (BDL). The BDL group received: L-ornithine (0.6 mg/kg/day), Phenylacetate (0.6 mg/kg/day), OP (0.6 mg/kg/day) or placebo (saline) for 5 days prior to sacrifice. Arterial ammonia, amino acids and liver biochemistry were measured. Expressions of GS and GA were determined by Western-blotting and activities by end-point methods in liver, muscle, gut, kidney, lung, and frontal cortex. In BDL rats, hepatic GS enzyme activity was reduced by more than 80% compared to sham rats. Further, in BDL rats GA activity was reduced in liver but increased in the gut, muscle and frontal cortex compared to sham rats. OP treatment resulted in a reduction in hyperammonemia in BDL rats, associated with increased GS activity in the muscle and reduced gut GA activity. In a rat model of chronic liver failure, hyperammonemia is associated with inadequate compensation by liver and muscle GS activity and increased gut GA activity. OP reduces plasma ammonia by increasing GS in the muscle and reducing GA activity in the gut providing additional insights into its mechanism of its action. GS and GA may serve as important future therapeutic targets for hyperammonemia in liver failure. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  15. Metallothionein induction reduces caspase-3 activity and TNFα levels with preservation of cognitive function and intact hippocampal neurons in carmustine-treated rats

    PubMed Central

    Aleisa, Abdulaziz M; Helal, Omayma K; Al-Rejaie, Salim S; Al-Yahya, Abdulaziz A; Al-Majed, Abdulhakeem A; Al-Shabanah, Othman A

    2009-01-01

    Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO4 and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of 60 male Wistar albino rats were randomly divided into four groups (15/group): The control group injected with single doses of normal saline (i.c.v) followed 24 h later by BCNU solvent (i.v). The second group administered ZnSO4 (0.1 µmol/10 µl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24 h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO4 (0.1 µmol/10 µl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFα), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO4 pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFα as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO4 + BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFα, MDA and caspase-3 activity with subsequent preservation of cognition. PMID:20046642

  16. Effect of N-methyl-D-aspartic acid on activity of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione level in selected organs of the mouse.

    PubMed

    Szaroma, Waldemar; Dziubek, K; Kapusta, E

    2014-09-01

    One of the major classes of ionotropic glutamate receptors is the class of N-methyl-D-aspartate receptors (NMDARs). Receptor activation recruits, via calcium signal transduction mechanisms which play important roles in oxidative metabolism, mitochondrial free radical production and occurrence of other mitochondrial factors which potentially contribute to excitotoxicity and neuronal death. In the present study, the effects of stimulation of NMDARs by applying N-methyl-D-aspartic acid (NMDA) in the brain, liver, kidneys and pancreas on change of the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) and in the amount of reduced glutathione (GSH) in blood, brain, liver and kidneys has been investigated. Statistically significant decrease of the activity of SOD, CAT and GSHPx and in the amount of reduced glutathione (GSH) was found in the examined organs after administration of NMDA, an agonist of NMDA receptors, demonstrating that NMDA administration compromises the antioxidant status in the investigated organs of the mouse.

  17. Honey reduces blood alcohol concentration but not affects the level of serum MDA and GSH-Px activity in intoxicated male mice models.

    PubMed

    Shi, Peiying; Chen, Bing; Chen, Conghai; Xu, Jingyang; Shen, Zhenhuang; Miao, Xiaoqing; Yao, Hong

    2015-07-14

    For a long time, honey was purportedly helpful to prevent drunkenness and relieve hangover symptoms. However, few of the assertions have experienced scientific assessment. The present study examined the effects of honey on intoxicated male mice. Low or high doses of lychee flower honey (2.19 or 4.39 g/kg body weight, respectively) were single orally administrated 30 min before the ethanol intoxication of mice, followed by recording the locomotor activity by autonomic activity instrument and observing the climbing ability after alcohol. On the other hand, 2.19 g/kg honey was single orally administrated 5 min after the ethanol intoxication of mice, followed by determining the ethanol concentration in mice blood. In addition, subacute alcoholism mice models were developed and after the treatment of 2.19 g/kg honey s.i.d for successive three days, the level of serum malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activity were detected in the models. Both of the two doses of honey increased the autonomic activity of alcoholized mice. Furthermore, the treatment of 2.19 g/kg honey could decrease significantly the blood ethanol concentration in intoxicated mice. The anti-intoxication activity of honey could be due to the effect of the fructose contained in the honey. Meanwhile, honey could not affect the serum MDA level and GSH-Px activity in alcoholism mice models. Honey indeed possesses anti-intoxication activity.

  18. 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

  19. 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

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

    2016-05-25

    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. 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). 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 groups will measure the

  20. Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes.

    PubMed

    Madduma Hewage, Susara Ruwan Kumara; Piao, Mei Jing; Kang, Kyoung Ah; Ryu, Yea Seong; Fernando, Pattage Madushan Dilhara Jayatissa; Oh, Min Chang; Park, Jeong Eon; Shilnikova, Kristina; Moon, Yu Jin; Shin, Dae O; Hyun, Jin Won

    2016-11-08

    Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKT-Nrf2, leading to elevated expression of GSH-synthesizing enzymes.

  1. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial.

    PubMed

    Johnston, Carol S; Barkyoumb, Gillean M; Schumacher, Sara S

    2014-07-09

    The early indications of vitamin C deficiency are unremarkable (fatigue, malaise, depression) and may manifest as a reduced desire to be physically active; moreover, hypovitaminosis C may be associated with increased cold duration and severity. This study examined the impact of vitamin C on physical activity and respiratory tract infections during the peak of the cold season. Healthy non-smoking adult men (18-35 years; BMI < 34 kg/m2; plasma vitamin C < 45 µmol/L) received either 1000 mg of vitamin C daily (n = 15) or placebo (n = 13) in a randomized, double-blind, eight-week trial. All participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily and the Godin Leisure-Time Exercise Questionnaire weekly. In the final two weeks of the trial, the physical activity score rose modestly for the vitamin C group vs. placebo after adjusting for baseline values: +39.6% (95% CI [-4.5,83.7]; p = 0.10). The number of participants reporting cold episodes was 7 and 11 for the vitamin C and placebo groups respectively during the eight-week trial (RR = 0.55; 95% CI [0.33,0.94]; p = 0.04) and cold duration was reduced 59% in the vitamin C versus placebo groups (-3.2 days; 95% CI [-7.0,0.6]; p = 0.06). These data suggest measurable health advantages associated with vitamin C supplementation in a population with adequate-to-low vitamin C status.

  2. Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats.

    PubMed

    Kim, Hye Sun; Paik, Man-Jeong; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

    2015-01-01

    We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on melatonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Urinary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Eight hours of nocturnal RFID exposure caused a significant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expression of AANAT were suppressed by exposure to RFID (p < 0. 05). Our results suggest that nocturnal RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

  3. 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.

  4. Immunization of teenagers with a fifth dose of reduced DTaP-IPV induces high levels of pertussis antibodies with a significant increase in opsonophagocytic activity.

    PubMed

    Aase, Audun; Herstad, Tove Karin; Merino, Samuel; Bolstad, Merete; Sandbu, Synne; Bakke, Hilde; Aaberge, Ingeborg S

    2011-08-01

    Waning vaccine-induced immunity against Bordetella pertussis is observed among adolescents and adults. A high incidence of pertussis has been reported in this population, which serves as a reservoir for B. pertussis. A fifth dose of reduced antigen of diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine was given as a booster dose to healthy teenagers. The antibody activity against B. pertussis antigens was measured prior to and 4 to 8 weeks after the booster by different assays: enzyme-linked immunosorbent assays (ELISAs) of IgG and IgA against pertussis toxin (PT) and filamentous hemagglutinin (FHA), IgG against pertactin (PRN), opsonophagocytic activity (OPA), and IgG binding to live B. pertussis. There was a significant increase in the IgG activity against PT, FHA, and PRN following the booster immunization (P < 0.001). The prebooster sera showed a geometric mean OPA titer of 65.1 and IgG binding to live bacteria at a geometric mean concentration of 164.9 arbitrary units (AU)/ml. Following the fifth dose, the OPA increased to a titer of 360.4, and the IgG concentration against live bacteria increased to 833.4 AU/ml (P < 0.001 for both). The correlation analyses between the different assays suggest that antibodies against FHA and PRN contribute the most to the OPA and IgG binding.

  5. The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels.

    PubMed

    Tam, R C; Ramasamy, K; Bard, J; Pai, B; Lim, C; Averett, D R

    2000-05-01

    The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the D-nucleoside ribavirin to its L-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.

  6. Leucine reduces reactive oxygen species levels via an energy metabolism switch by activation of the mTOR-HIF-1α pathway in porcine intestinal epithelial cells.

    PubMed

    Hu, Jun; Nie, Yangfan; Chen, Shifeng; Xie, Chunlin; Fan, Qiwen; Wang, Zhichang; Long, Baisheng; Yan, Guokai; Zhong, Qing; Yan, Xianghua

    2017-08-01

    Leucine serves not only as a substrate for protein synthesis, but also as a signal molecule involved in protein metabolism. However, whether the levels of cellular reactive oxygen species (ROS), which have damaging effects on cellular DNA, proteins, and lipids, are regulated by leucine is still unclear. Here, we report that leucine supplementation reduces ROS levels in intestinal epithelial cells of weaned piglets. A proteomics analysis revealed that leucine supplementation induces an energy metabolism switch from oxidative phosphorylation (OXPHOS) towards glycolysis. The leucine-induced ROS reduction and the energy metabolism switch were further validated in cultured cells. Mechanistically, our data revealed that leucine-induced ROS reduction actually depends on the energy metabolism switch from OXPHOS towards glycolysis through the mechanistic target of rapamycin (mTOR)- hypoxia-inducible factor-1alpha (HIF-1α) pathway. These findings reveal a vital regulatory role of leucine as the signal molecule involved in an energy metabolism switch in mammals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The effects of exogenous glutathione on reduced glutathione level, glutathione peroxidase and glutathione reductase activities of rats with different ages and gender after whole-body Γ-irradiation.

    PubMed

    Erden Inal, Mine; Akgün, Asiye; Kahraman, Ahmet

    2003-07-01

    Age-and gender-related changes on reduced glutathione (GSH) level, glutathione peroxidase (GPx) and glutathione reductase (GR) activities in the liver of rat exposed to different dose of whole-body g-ray irradiation were determined. In addition, the effect of administration of exogenous GSH on endogenous GSH levels, GPx and GR activities was investigated. For this aim, male and female rats aged 1 and 5 moths were divided into two groups as g-ray and g-ray+GSH. Both groups were again divided into four groups as irradiated with 2, 4, 6 and 8 Gy doses. GSH level and GPx activity did not change with age while GR activity was decreased with age. Gender-dependent changes in GPx and GR activities were observed, but GSH values were not affect by sex. GSH levels, GPx and GR activities were not observed dose-associated changes of g-irradiation. GSH level and GPx activity in the 8Gy group were increased by GSH. GR activities of old male rats were found to be increased by glutathione in the 6 and 8Gy groups. These results indicate that radiation and administration of exogenous GSH affect gender-and age-dependent GSH level, GPx and GR activities in the rats.

  8. Western Diet Chow Consumption in Rats Induces Striatal Neuronal Activation While Reducing Dopamine Levels without Affecting Spatial Memory in the Radial Arm Maze

    PubMed Central

    Nguyen, Jason C. D.; Ali, Saher F.; Kosari, Sepideh; Woodman, Owen L.; Spencer, Sarah J.; Killcross, A. Simon; Jenkins, Trisha A.

    2017-01-01

    Rats fed high fat diets have been shown to be impaired in hippocampal-dependent behavioral tasks, such as spatial recognition in the Y-maze and reference memory in the Morris water maze (MWM). It is clear from previous studies, however, that motivation and reward factor into the memory deficits associated with obesity and high-fat diet consumption, and that the prefrontal cortex and striatum and neurotransmitter dopamine play important roles in cognitive performance. In this series of studies we extend our research to investigate the effect of a high fat diet on striatal neurochemistry and performance in the delayed spatial win-shift radial arm maze task, a paradigm highly reliant on dopamine-rich brain regions, such as the striatum after high fat diet consumption. Memory performance, neuronal activation and brain dopaminergic levels were compared in rats fed a “Western” (21% fat, 0.15% cholesterol) chow diet compared to normal diet (6% fat, 0.15% cholesterol)-fed controls. Twelve weeks of dietary manipulation produced an increase in weight in western diet-fed rats, but did not affect learning and performance in the delayed spatial win-shift radial arm maze task. Concurrently, there was an observed decrease in dopamine levels in the striatum and a reduction of dopamine turnover in the hippocampus in western diet-fed rats. In a separate cohort of rats Fos levels were measured after rats had been placed in a novel arena and allowed to explore freely. In normal rats, this exposure to a unique environment did not affect neuronal activation. In contrast, rats fed a western diet were found to have significantly increased Fos expression in the striatum, but not prefrontal cortex or hippocampus. Our study demonstrates that while western diet consumption in rats produces weight gain and brain neuronal and neurotransmitter changes, it did not affect performance in the delayed spatial win-shift paradigm in the radial arm maze. We conclude that modeling the cognitive

  9. Western Diet Chow Consumption in Rats Induces Striatal Neuronal Activation While Reducing Dopamine Levels without Affecting Spatial Memory in the Radial Arm Maze.

    PubMed

    Nguyen, Jason C D; Ali, Saher F; Kosari, Sepideh; Woodman, Owen L; Spencer, Sarah J; Killcross, A Simon; Jenkins, Trisha A

    2017-01-01

    Rats fed high fat diets have been shown to be impaired in hippocampal-dependent behavioral tasks, such as spatial recognition in the Y-maze and reference memory in the Morris water maze (MWM). It is clear from previous studies, however, that motivation and reward factor into the memory deficits associated with obesity and high-fat diet consumption, and that the prefrontal cortex and striatum and neurotransmitter dopamine play important roles in cognitive performance. In this series of studies we extend our research to investigate the effect of a high fat diet on striatal neurochemistry and performance in the delayed spatial win-shift radial arm maze task, a paradigm highly reliant on dopamine-rich brain regions, such as the striatum after high fat diet consumption. Memory performance, neuronal activation and brain dopaminergic levels were compared in rats fed a "Western" (21% fat, 0.15% cholesterol) chow diet compared to normal diet (6% fat, 0.15% cholesterol)-fed controls. Twelve weeks of dietary manipulation produced an increase in weight in western diet-fed rats, but did not affect learning and performance in the delayed spatial win-shift radial arm maze task. Concurrently, there was an observed decrease in dopamine levels in the striatum and a reduction of dopamine turnover in the hippocampus in western diet-fed rats. In a separate cohort of rats Fos levels were measured after rats had been placed in a novel arena and allowed to explore freely. In normal rats, this exposure to a unique environment did not affect neuronal activation. In contrast, rats fed a western diet were found to have significantly increased Fos expression in the striatum, but not prefrontal cortex or hippocampus. Our study demonstrates that while western diet consumption in rats produces weight gain and brain neuronal and neurotransmitter changes, it did not affect performance in the delayed spatial win-shift paradigm in the radial arm maze. We conclude that modeling the cognitive decline

  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

    2014-08-20

    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.

  11. Reducing activity, glucose metabolism and acid tolerance response of Bacillus cereus grown at various pH and oxydo-reduction potential levels.

    PubMed

    Le Lay, Julien; Bahloul, Halim; Sérino, Sylvie; Jobin, Michel; Schmitt, Philippe

    2015-04-01

    Bacillus cereus is a major foodborne bacterial pathogen able to survive a large number of physical-chemical stresses. B. cereus encounters different pH and redox potential (Eh7) levels during its passage through the gastrointestinal tract. Analysis of the combined influence of pH and redox stresses on B. cereus F4430/73 physiology found that B. cereus F4430/73 growth at pH 7.0 at 37 °C had strong reducing capacities, with a total change of 315 mV from an initial redox value of +214 ± 17 mV. The combination of low Eh7 and low pH led to a drastic reduction of growth parameters compared to oxidative Eh7 and neutral pH. Metabolic analysis showed that low pH significantly modifies glucose fermentative metabolism, with changes including decreased production of acid metabolite (acetate, lactate, formate) and increased production of 2,3-butanediol. Low Eh7 slightly enhanced the acid-tolerance response of B. cereus whereas low pH pre-adaptation led to thermal stress cross-protection. These results highlight new mechanisms that bring fresh insight into B. cereus pH and redox stress adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Increased physical activity reduces prevalence of periodontitis.

    PubMed

    Al-Zahrani, Mohammad S; Borawski, Elaine A; Bissada, Nabil F

    2005-10-01

    Physical activity has been shown to have a protective relationship with several chronic diseases. Recently, physical activity was also found to reduce the risk of periodontitis in a study in male health professionals. However, the relationship between physical activity and periodontitis in a diverse group of individuals is not thoroughly examined. The purpose of this study was to examine if there is an association between sustained physical activity and periodontitis in a subset of the third national health and nutrition examination survey (NHANES III). NHANES III participants 18 years of age or older who had had a periodontal examination and reported to have a similar physical activity (or inactivity) level for 10 years or longer were selected (n=2521). Multivariable logistic regression analysis was used to estimate the association between physical activity and periodontitis. The analysis was adjusted for: age, gender, race, education, smoking, body mass index, poverty index, vitamin use, healthy eating index, time since last dental visit, gingival bleeding, and dental calculus. Engaging in the recommended level of physical activity was significantly associated with lower periodontitis prevalence (OR=0.58, 95% CI, 0.35-0.96). Smoking, however, was found to modify this relationship. The association was strong and significant among never (OR=0.46, 95% CI, 0.23-0.93) and former smokers (OR=0.26, 95% CI: 0.09-0.72), but not among current smokers (OR=1.10, 95% CI: 0.48-2.53). These results suggest that engaging in the recommended level of exercise is associated with lower periodontitis prevalence, especially among never and former smokers.

  13. Reduced levels of Dusp3/Vhr phosphatase impair normal spindle bipolarity in an Erk1/2 activity-dependent manner.

    PubMed

    Tambe, Mahesh Balasaheb; Narvi, Elli; Kallio, Marko

    2016-08-01

    Dual specificity phosphatase-3 (Dusp3/Vhr) regulates cell cycle progression by counteracting the effects of mitogen-activated protein kinases (Mapk) Erk1/2 and Jnk. Despite the known upregulation of Dusp3 at M phase in mammalian cells, its mitotic functions are poorly characterized. Here, we report that loss of Dusp3 by RNAi leads to the formation of multipolar spindles in human mitotic cancer cells in an Erk1/2-dependent manner. In the phosphatase-silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis.

  14. Reduced levels of ATF-2 predispose mice to mammary tumors.

    PubMed

    Maekawa, Toshio; Shinagawa, Toshie; Sano, Yuji; Sakuma, Takahiko; Nomura, Shintaro; Nagasaki, Koichi; Miki, Yoshio; Saito-Ohara, Fumiko; Inazawa, Johji; Kohno, Takashi; Yokota, Jun; Ishii, Shunsuke

    2007-03-01

    Transcription factor ATF-2 is a nuclear target of stress-activated protein kinases, such as p38, which are activated by various extracellular stresses, including UV light. Here, we show that ATF-2 plays a critical role in hypoxia- and high-cell-density-induced apoptosis and the development of mammary tumors. Compared to wild-type cells, Atf-2(-/-) mouse embryonic fibroblasts (MEFs) were more resistant to hypoxia- and anisomycin-induced apoptosis but remained equally susceptible to other stresses, including UV. Atf-2(-/-) and Atf-2(+/-) MEFs could not express a group of genes, such as Gadd45alpha, whose overexpression can induce apoptosis, in response to hypoxia. Atf-2(-/-) MEFs also had a higher saturation density than wild-type cells and expressed lower levels of Maspin, the breast cancer tumor suppressor, which is also known to enhance cellular sensitivity to apoptotic stimuli. Atf-2(-/-) MEFs underwent a lower degree of apoptosis at high cell density than wild-type cells. Atf-2(+/-) mice were highly prone to mammary tumors that expressed reduced levels of Gadd45alpha and Maspin. The ATF-2 mRNA levels in human breast cancers were lower than those in normal breast tissue. Thus, ATF-2 acts as a tumor susceptibility gene of mammary tumors, at least partly, by activating a group of target genes, including Maspin and Gadd45alpha.

  15. Deficiency in lysophosphatidylcholine acyltransferase 3 reduces plasma levels of lipids by reducing lipid absorption in mice.

    PubMed

    Li, Zhiqiang; Jiang, Hui; Ding, Tingbo; Lou, Caixia; Bui, Hai H; Kuo, Ming-Shang; Jiang, Xian-Cheng

    2015-11-01

    Phosphatidylcholines (PCs) are structural and functional constituents of cell membranes. The activity of acyltransferase (lysophosphatidylcholine acyltransferase [LPCAT]) is required for addition of polyunsaturated fatty acids to the sn-2 position of PCs and is therefore required to maintain cell membrane structure and function. LPCAT3 is the most abundant isoform of LPCAT in the small intestine and liver, which are important sites of plasma lipoprotein metabolism. We investigated the effects of Lpcat3 disruption on lipid metabolism in mice. We disrupted the gene Lpcat3 in C57BL/6J mice to create LPCAT3 knockout (KO) mice. Livers and small intestinal tissues were collected from LPCAT3 KO and C57BL/6J parental strain (controls), and levels of LPCAT messenger RNAs and protein were measured. Levels of lipids and lipoproteins were measured in plasma samples. We isolated enterocytes from mice and measured levels of RNAs and proteins involved in lipid uptake by real-time polymerase chain reaction and immunoblot assays, respectively. We assessed lipid absorption and PC subspecies in the enterocyte plasma membrane using liquid chromatography with tandem mass spectometry. LPCAT3 KO mice survived only 3 weeks after birth. Oil Red O staining showed that the control but not LPCAT3 KO mice accumulated lipids in the small intestine; levels of Niemann-Pick C1-like 1 (NPC1L1) and fatty acid transporter protein 4 (FATP4), which regulate lipid uptake, were greatly reduced in the small intestines of LPCAT3 KO mice. Oral administration of PC and olive oil allowed the LPCAT3 KO mice to survive with the same body weights as controls, but the KO mice had shorter and wider small-intestinal villi and longer and bigger small intestines. Plasma membranes of enterocytes from LPCAT3 KO mice also had significant reductions in the composition of polyunsaturated PCs and reduced levels of NPC1L1, CD36, and FATP4 proteins. These reductions were associated with reduced intestinal uptake of lipid by

  16. Reduced DNA topoisomerase II activity in ataxia-telangiectasia cells.

    PubMed Central

    Singh, S P; Mohamed, R; Salmond, C; Lavin, M F

    1988-01-01

    Considerable evidence supports a defect at the level of chromatin structure or recognition of that structure in cells from patients with the human genetic disorder ataxia-telangiectasia. Accordingly, we have investigated the activities of enzymes that alter the topology of DNA in Epstein Barr Virus-transformed lymphoblastoid cells from patients with this syndrome. Reduced activity of DNA topoisomerase II, determined by unknotting of P4 phage DNA, was observed in partially purified extracts from 5 ataxia-telangiectasia cell lines. The levels of enzyme activity was reduced substantially in 4 of these cell lines and to a lesser extent in the other cell line compared to controls. DNA topoisomerase I, assayed by relaxation of supercoiled DNA, was found to be present at comparable levels in both cell types. Reduced activity of topoisomerase II in ataxia-telangiectasia is compatible with the molecular, cellular and clinical changes described in this syndrome. Images PMID:2836804

  17. Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine.

    PubMed

    Larsen, K; Najle, R; Lifschitz, A; Virkel, G

    2012-11-01

    Glyphosate (GLP), the active ingredient of many weed killing formulations, is a broad spectrum herbicide compound. Wistar rats were exposed during 30 or 90 days to the highest level (0.7 mg/L) of GLP allowed in water for human consumption (US EPA, 2011) and a 10-fold higher concentration (7 mg/L). The low levels of exposure to the herbicide did not produce histomorphological changes. The production of TBARS was similar or tended to be lower compared to control animals not exposed to the herbicide. In rats exposed to GLP, increased levels of reduced glutathione (GSH) and enhanced glutathione peroxidase (GPx) activity may act as a protective mechanism against possible detrimental effects of the herbicide. Overall, this work showed certain biochemical modifications, even at 3-20-fold lower doses of GLP than the oral reference dose of 2mg/kg/day (US EPA, 1993). The toxicological significance of these findings remains to be clarified. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. 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.)

  19. Activating Attachments Reduces Memories of Traumatic Images

    PubMed Central

    Foord, Rachael

    2016-01-01

    Emotional memories, and especially intrusive memories, are a common feature of many psychological disorders, and are overconsolidated by stress. Attachment theory posits that activation of mental representations of attachment figures can reduce stress and boost coping. This study tested the proposition that attachment activation would reduce consolidation of emotional and intrusive memories. Sixty-seven undergraduate students viewed subliminal presentations of traumatic and neutral images, which were preceded by subliminal presentations of either attachment-related images or non-attachment-related images; free recall and intrusive memories were assessed two days later. Participants with low avoidant attachment tendencies who received the attachment primes recalled fewer memories and reported fewer intrusions than those who received the non-attachment primes. Unexpectedly, those with high anxious attachment tendencies reported fewer memories. These findings generally accord with attachment theory, and suggest that consolidation of emotional memories can be moderated by activation of attachment representations. PMID:27631498

  20. Activating Attachments Reduces Memories of Traumatic Images.

    PubMed

    Bryant, Richard A; Foord, Rachael

    2016-01-01

    Emotional memories, and especially intrusive memories, are a common feature of many psychological disorders, and are overconsolidated by stress. Attachment theory posits that activation of mental representations of attachment figures can reduce stress and boost coping. This study tested the proposition that attachment activation would reduce consolidation of emotional and intrusive memories. Sixty-seven undergraduate students viewed subliminal presentations of traumatic and neutral images, which were preceded by subliminal presentations of either attachment-related images or non-attachment-related images; free recall and intrusive memories were assessed two days later. Participants with low avoidant attachment tendencies who received the attachment primes recalled fewer memories and reported fewer intrusions than those who received the non-attachment primes. Unexpectedly, those with high anxious attachment tendencies reported fewer memories. These findings generally accord with attachment theory, and suggest that consolidation of emotional memories can be moderated by activation of attachment representations.

  1. Using stand-level optimization to reduce crown fire hazard

    Treesearch

    David H. Graetz; John Sessions; Steven L. Garman

    2007-01-01

    This study evaluated the ability to generate prescriptions for a wide variety of stands when the goal is to reduce crown fire potential. Forest managers charged with reducing crown fire potential while providing for commodity and ecological production have been hampered by the complexity of possible management options. A program called Stand-Level Optimization with...

  2. Reducing Abstraction Level When Learning Abstract Algebra Concepts.

    ERIC Educational Resources Information Center

    Hazzan, Orit

    1999-01-01

    Presents a theoretical framework based on interviews with undergraduate students and written questionnaires to study how undergraduate students cope with abstract algebra concepts. Indicates that students' responses can be interpreted as a result of reducing the level of abstraction. Examines the theme of reducing abstraction based on three…

  3. Children and youth do not compensate for an imposed bout of prolonged sitting by reducing subsequent food intake or increasing physical activity levels: a randomised cross-over study.

    PubMed

    Saunders, Travis J; Chaput, Jean-Philippe; Goldfield, Gary S; Colley, Rachel C; Kenny, Glen P; Doucet, Eric; Tremblay, Mark S

    2014-02-01

    The behavioural impact of an imposed bout of prolonged sitting is yet to be investigated in the paediatric population. The objective of the present study was to determine the acute effect of prolonged sitting on ad libitum food intake and spontaneous physical activity (PA) levels in healthy children and youth. A total of twenty healthy youth (twelve males and eight females) aged 10-14 years, with a mean BMI of 18·6 (sd 4·3) kg/m², were exposed to three experimental conditions in a random order: (1) a day of uninterrupted sitting (Sedentary); (2) a day of sitting interrupted with a 2 min light-intensity walk break every 20 min (Breaks); (3) a day of sitting interrupted with a 2 min light-intensity walk break every 20 min as well as 2 × 20 min of moderate-intensity PA (Breaks+PA). Food intake (ad libitum buffet meal) and PA (accelerometry for 24 h) were assessed following exposure to each experimental condition. Despite significant differences in sedentary behaviour and activity levels during the three in-laboratory sessions (all P< 0·01), we did not observe any differences in ad libitum food intake immediately following exposure to each experimental condition or any changes in the levels of sedentary behaviour or PA in the 24 h following exposure to each experimental condition (all P>0·25). These findings suggest that children and youth may not compensate for an imposed bout of sedentary behaviour by reducing subsequent food intake or increasing PA levels.

  4. Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption

    PubMed Central

    Smith-Anttila, Casey J.A.; Nordenankar, Karin; Arvidsson, Emma; Mahmoudi, Souha; Zampera, André; Wärner Jonsson, Hanna; Bergquist, Jonas; Lévesque, Daniel; Andersson, Malin; Dumas, Sylvie

    2016-01-01

    The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson’s disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system. PMID:27699212

  5. 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.

  6. Periodontal Treatment Reduces Matrix Metalloproteinase Levels in Localized Aggressive Periodontitis

    PubMed Central

    Gonçalves, Patricia Furtado; Huang, Hong; McAninley, Suzanna; Alfant, Barnett; Harrison, Peter; Aukhil, Ikramuddin; Walker, Clay; Shaddox, Luciana Macchion

    2015-01-01

    Background Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal destruction and inflammation. We have previously reported high MMP levels in African-American children with localized aggressive periodontitis (LAP). However, little is known about MMP reductions in gingival crevicular fluid (GCF) after therapy. This study aimed to evaluate MMP levels in the GCF following treatment of LAP and to correlate these levels with clinical response. Methods GCF samples were collected from 29 African-American individuals diagnosed with LAP. GCF was collected from one diseased site (pocket depth [PD]>4mm, bleeding on probing [BoP] and clinical attachment level [CAL] ≥2mm) and one healthy site (PD≤3mm, no BoP) from each individual at baseline, 3 and 6 months after periodontal treatment, which consisted of full-mouth SRP and systemic antibiotics. The volume of GCF was controlled using a calibrated gingival fluid meter and levels of MMP-1, 2, 3, 8, 9, 12 and 13 were assessed using fluorometric kits. Results MMP-1, 8, 9 12, and 13 levels were reduced significantly up to 6 months, at which point were comparable with healthy sites. Significant correlations were noted between MMP-2, 3, 8, 9, 12 and 13 levels and % of sites with PD>4mm. MMP-3, 12 and 13 levels also correlated with mean pocket depth of affected sites. Conclusion Treatment of LAP with SRP and systemic antibiotics was effective in reducing the local levels specific MMPs in African-American individuals, which correlated positively with some clinical parameters. PMID:23537121

  7. Reducing Indoor Noise Levels Using People's Perception on Greenery

    NASA Astrophysics Data System (ADS)

    Mediastika, Christina E.; Binarti, Floriberta

    2013-12-01

    Employees working in cubicles of open-plan offices in Indonesia were studied in regard to their perception on the ability of indoor greenery to reduce noise levels. Sansevieria trifasciata and Scindapsus sp were used. Each was placed in the cubicle and noise levels were measured without plants, with Sansevieria, and with Scindapsus in place. The meters showed very insignificant difference. However, responses to surveys indicated a perception of lower noise in the presence of greenery. This seemed to be supported by prior knowledge and preconception and may be useful in creating a "quieter" indoor environment.

  8. 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

  9. Mucin Binding Reduces Colistin Antimicrobial Activity.

    PubMed

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

    2015-10-01

    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.

  10. [Phytosterols: another way to reduce LDL cholesterol levels].

    PubMed

    Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror

    2013-12-01

    Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

  11. 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

  12. Dimensions of Temperamental Activity Level and Adjustment

    ERIC Educational Resources Information Center

    Teglasi, Hedwig; French, Mila; Lohr, Lauren; Miller, Karen J.; Erwin, Holly Drewer; Rothman, Lee; Denny, Michelle

    2008-01-01

    The relationship between children's activity level and adjustment has been based on a one-dimensional conceptualization of activity level and warrants re-examination. Current questionnaires conflate amount of physical movement with its appropriateness to the context, making it impossible to tell which aspect of activity level accounts for its…

  13. 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

  14. 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

  15. Reduced serum levels of adiponectin in tension-type headache.

    PubMed

    Domingues, Renan B; Duarte, Halina; Rocha, Natália P; Teixeira, Antonio L

    2015-04-01

    Inflammatory mediators have been studied in tension type headache (TTH) pathophysiology; however, their role is not yet well established. The aim of the present study was to investigate adiponectin (ADP) and its association with clinical parameters and psychiatric comorbidities in TTH patients. This was a cross sectional study including TTH patients and controls. Beck Depression (BDI) and Anxiety (BAI) Inventories, and Headache Impact Test (HIT-6) were recorded. Serum levels of ADP were measured by ELISA. Forty-eight TTH patients and forty-eight controls without headache were enrolled in the study. ADP levels were significantly lower among patients with TTH [31.1 (20.4-69.20) versus 37.8 (24.9-71.4) ng/mL (P=0.008)]. ADP levels were not influenced by BDI and BAI scores, body mass index (BMI), or HIT-6. ADP levels were reduced in TTH, independently of psychiatric comorbidities, BMI, and headache impact. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. 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

  17. 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.

  18. 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.

  19. Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders.

    PubMed

    Rubin, Leah H; Carter, C Sue; Bishop, Jeffrey R; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Hill, S Kristian; Ruocco, Anthony C; Keedy, Sarah K; Reilly, James L; Keshavan, Matcheri S; Pearlson, Godfrey D; Tamminga, Carol A; Gershon, Elliot S; Sweeney, John A

    2014-11-01

    Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h(2) = 0.79, P = 3.97e-15) and AVP (h(2) = 0.78, P = 3.93e-11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

    PubMed Central

    Rubin, Leah H.; Carter, C. Sue; Bishop, Jeffrey R.; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L.; Hill, S. Kristian; Ruocco, Anthony C.; Keedy, Sarah K.; Reilly, James L.; Keshavan, Matcheri S.; Pearlson, Godfrey D.; Tamminga, Carol A.; Gershon, Elliot S.; Sweeney, John A.

    2014-01-01

    Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h 2 = 0.79, P = 3.97e−15) and AVP (h 2 = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high. PMID:24619535

  1. 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)

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Lower levels of sodium intake and reduced cardiovascular risk.

    PubMed

    Cook, Nancy R; Appel, Lawrence J; Whelton, Paul K

    2014-03-04

    Recent studies have raised the possibility of adverse effects of low sodium, particularly <2300 mg/d, on cardiovascular disease; however, these paradoxical findings might have resulted from suboptimal measurement of sodium and potential biases related to indication or reverse causation. Phases 1 and 2 of the Trials of Hypertension Prevention (TOHP) collected multiple 24-hour urine specimens among prehypertensive individuals. During extended post-trial surveillance, 193 cardiovascular events or cardiovascular disease deaths occurred among 2275 participants not in a sodium reduction intervention with 10 (TOHP II) or 15 (TOHP I) years of post-trial follow-up. Median sodium excretion was 3630 mg/d, with 1.4% of the participants having intake <1500 mg/d and 10% <2300 mg/d, consistent with national levels. Compared with those with sodium excretion of 3600 to <4800 mg/d, risk for those with sodium <2300 mg/d was 32% lower after multivariable adjustment (hazard ratio, 0.68; 95% confidence interval, 0.34-1.37; P for trend=0.13). There was a linear 17% increase in risk per 1000 mg/d increase in sodium (P=0.05). Spline curves supported a linear association of sodium with cardiovascular events, which continued to decrease from 3600 to 2300 and 1500 mg/d, although the data were sparse at the lowest levels. Controlling for creatinine levels had little effect on these results. Results from the TOHP studies, which overcome the major methodological challenges of prior studies, are consistent with overall health benefits of reducing sodium intake to the 1500 to 2300 mg/d range in the majority of the population, in agreement with current dietary guidelines.

  9. High levels of B cell activating factor during the peritransplantation period are associated with a reduced incidence of acute graft-versus-host disease following myeloablative allogeneic stem cell transplantation.

    PubMed

    Cho, Byung-Sik; Min, Chang-Ki; Kim, Hee-Je; Lee, Seok; Kim, Yoo-Jin; Lim, Ji-Young; Jeong, Dae-Chul; Cho, Bin; Kim, Hack-Ki; Eom, Ki-Seong; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Kim, Chun-Choo; Chung, Nak-Gyun

    2010-05-01

    B cell activating factor (BAFF), also known as B cell survival and activation factor, is associated with autoimmune disease and chronic graft-versus-host disease (cGVHD). T cells are known to be modulated by soluble BAFF (sBAFF). Considering the possible association of sBAFF with T cell as well as B cell function, sBAFF during the peritransplantation period may affect the development of acute GVHD (aGVHD). To test this hypothesis, we evaluated 45 patients who had undergone myeloablative (MA) allogeneic stem cell transplantation (SCT) for hematologic malignancy. Serum sBAFF levels were measured before conditioning and on day 0, day +7, and day +14. Thirty-three of the 45 patients (cumulative incidence, 73%) developed aGVHD between 16 days and 98 days posttransplantation. Repeated-measures analysis of variance revealed significantly lower sBAFF levels during the peritransplantation period in patients with aGVHD than in those without aGVHD (P=.001). Receiver operating characteristic curve analysis revealed that sBAFF levels at every time point were available for the prediction of aGVHD development, and that patients with a sBAFF level >43 pg/mL at each time point (which could ensure 75% sensitivity and 73%-82% specificity for the prediction of aGVHD at every time point) had a significantly lower cumulative incidence of aGVHD. This study is the first to demonstrate that sBAFF level during the peritransplantation period not only may be predictive of aGVHD, but also may have a protective effect against aGVHD in humans. Further investigation is needed to confirm our findings. Copyright 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. 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

  12. Cytoplasmic localized infected cell protein 0 (bICP0) encoded by bovine herpesvirus 1 inhibits beta interferon promoter activity and reduces IRF3 (interferon response factor 3) protein levels

    PubMed Central

    da Silva, Leticia Frizzo; Gaudreault, Natasha; Jones, Clinton

    2011-01-01

    Bovine herpesvirus 1 (BHV-1), an alpha-herpesvirinae subfamily member, establishes a life-long latent infection in sensory neurons. Periodically, BHV-1 reactivates from latency, infectious virus is spread, and consequently virus transmission occurs. BHV-1 acute infection causes upper respiratory track infections and conjunctivitis in infected cattle. As a result of transient immunesuppression, BHV-1 infections can also lead to life-threatening secondary bacterial pneumonia that is referred to as bovine respiratory disease. The infected cell protein 0 (bICP0) encoded by BHV-1 reduces human beta-interferon (IFN-β) promoter activity, in part, by inducing degradation of interferon response factor 3 (IRF3) and interacting with IRF7. In contrast to humans, cattle contain three IFN-β genes. All three bovine IFN-β proteins have anti-viral activity: but each IFN-β gene has a distinct transcriptional promoter. We have recently cloned and characterized the three bovine IFN-β promoters. Relative to the human IFN-β promoter, each of the three IFN-β promoters contain differences in the four positive regulatory domains that are required for virus-induced activity. In this study, we demonstrate that bICP0 effectively inhibits bovine IFN-β promoter activity following transfection of low passage bovine cells with interferon response factor 3 (IRF3) or IRF7. A bICP0 mutant that localizes to the cytoplasm inhibits bovine IFN-β promoter activity as efficiently as wt bICP0. The cytoplasmic localized bICP0 protein also induced IRF3 degradation with similar efficiency as wt bICP0. In summary, these studies suggested that cytoplasmic localized bICP0 plays a role in inhibiting the IFN-β response during productive infection. PMID:21689696

  13. 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.

  14. 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

  15. Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

    PubMed

    Ng, Wan-Fai; Miller, Ariana; Bowman, Simon J; Price, Elizabeth J; Kitas, George D; Pease, Colin; Emery, Paul; Lanyon, Peter; Hunter, John; Gupta, Monica; Giles, Ian; Isenberg, David; McLaren, John; Regan, Marian; Cooper, Annie; Young-Min, Steven A; McHugh, Neil; Vadivelu, Saravanan; Moots, Robert J; Coady, David; MacKay, Kirsten; Dasgupta, Bhaskar; Sutcliffe, Nurhan; Bombardieri, Michele; Pitzalis, Costantino; Griffiths, Bridget; Mitchell, Sheryl; Miyamoto, Samira Tatiyama; Trenell, Michael

    2017-04-01

    The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

  16. Myo-inositol reduces β-catenin activation in colitis

    PubMed Central

    Bradford, Emily M; Thompson, Corey A; Goretsky, Tatiana; Yang, Guang-Yu; Rodriguez, Luz M; Li, Linheng; Barrett, Terrence A

    2017-01-01

    AIM To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-cateninS552 as a biomarker of recurrent dysplasia. METHODS We examined the effects of dietary myo-inositol treatment on inflammation, pβ-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, pβ-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, pβ-cateninS552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION Enumerating crypts with increased numbers of pβ-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials. PMID:28811707

  17. 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

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

    PubMed

    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

    2015-03-10

    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.

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

    DTIC Science & Technology

    2009-05-01

    decibels at a moderate airspeed, level flight condition at 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, generating counter-acting acoustic pulses that partially offset the negative...by up to 6 decibels at a moderate airspeed, level flight condition at advance ratio of 0.30. Reduced noise levels were attributed to selective active

  20. Active gas aspiration to reduce pain after laparoscopic cholecystectomy.

    PubMed

    Atak, Ibrahim; Ozbagriacik, Mustafa; Akinci, Omer Faruk; Bildik, Nejdet; Subasi, Ismail Ege; Ozdemir, Mehtap; Ayta, Nejla Inan

    2011-04-01

    To investigate to what effect active subdiaphragmatic gas aspiration reduces pain after a laparoscopic cholecystectomy. A total of 104 patients undergoing laparoscopic cholecystectomy were randomly placed into 2 groups. Group I included active subdiaphragmatic gas aspiration (n=52) while group II included simple evacuation (n=52) without any additional procedures. Postoperative analgesic requirements were recorded and the level of postoperative abdominal and shoulder pain was assessed using a numeric scale after 24 postoperative hours. Data were analyzed using the χ test for nonparametric data and Student t test for parametric data. Age, volume of CO2 used during surgery, and operation duration were similar in the 2 groups. The simple evacuation group (group II) experienced more shoulder and abdominal pain postoperatively when compared with the active subdiaphragmatic aspiration group (group I) and had a higher use of analgesics during the postoperative period. Active subdiaphragmatic gas aspiration after a laparoscopic cholecystectomy is a simple procedure that can effectively reduce postoperative abdominal and shoulder pain and as a result the need for analgesics.

  1. 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

  2. Reduced serum hepcidin levels in patients with chronic hepatitis C

    PubMed Central

    Girelli, Domenico; Pasino, Michela; Goodnough, Julia B.; Nemeth, Elizabeta; Guido, Maria; Castagna, Annalisa; Busti, Fabiana; Campostrini, Natascia; Martinelli, Nicola; Vantini, Italo; Corrocher, Roberto; Ganz, Tomas; Fattovich, Giovanna

    2009-01-01

    Background/Aims Patients with chronic hepatitis C (CHC) often have increased liver iron, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is the major regulator of iron metabolism and inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin). Methods Using a recently validated immunoassay, we measured s-hepcidin levels in 81 untreated CHC patients and 57 controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score. Results S-hepcidin was significantly lower in CHC patients than in controls (geometric means with 95% confidence intervals: 33.7, 21.5–52.9 vs. 90.9, 76.1–108.4 ng/mL, respectively; p < 0.001). In CHC patients, s-hepcidin significantly correlated with serum ferritin and histological total iron score, but not with s-interleukin-6. After stratification for ferritin quartiles, s-hepcidin increased significantly across quartiles in both controls and CHC patients (chi for trend, p < 0.001). However, in CHC patients, s-hepcidin was significantly lower than in controls for each corresponding quartile (analysis of variance, p < 0.001). Conclusions These results, together with very recent studies in animal and cellular models, indicate that although hepcidin regulation by iron stores is maintained in CHC, the suppression of this hormone by hepatitis C virus is likely an important factor in liver iron accumulation in this condition. PMID:19729219

  3. 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…

  4. Reduced Arylsulfatase B Activity in Leukocytes from Cystic Fibrosis Patients

    PubMed Central

    Sharma, Girish; Burke, Jenifer; Bhattacharyya, Sumit; Sharma, Neha; Katyal, Shivani; Park, R. Lucy; Tobacman, Joanne

    2013-01-01

    Summary The enzyme Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) removes 4-sulfate groups from chondroitin-4-sulfate and dermatan sulfate and is required for the degradation of these sulfated glycosaminoglycans (GAGs). Since these GAGs accumulate in patients with Cystic Fibrosis (CF), we investigated the activity of ARSB in leukocytes of patients with CF, to consider if reduced activity of ARSB might contribute to the pathophysiology of CF. Previous cell-based experiments had demonstrated that when the deficiency of the cystic fibrosis transmembrane regulator (CFTR) was corrected in bronchial epithelial cells, the ARSB activity increased significantly. De-identified, citrated blood samples were collected from 16 children with cystic fibrosis and 31 control subjects, seen in the Pediatric Clinic at Rush University Medical Center. Polymorphonuclear (PMN) and mononuclear cell (MC) populations were separated by density gradient, and blinded determinations of ARSB activity were performed using the exogenous substrate 4-methylumbilliferyl sulfate. Interleukin-6 was measured in the plasma samples by ELISA. ARSB activity was significantly less in the PMN and MC from the CF patients than controls (p<0.0001, unpaired t-test, two-tailed). Interleukin-6 levels in plasma were significantly greater in the CF population (p<0.001). Mean age, age range, and male:female ratio of CF patients and controls were similar, and no association of ARSB activity with age, gender, or CFTR genotype was evident. Since recombinant human ARSB is used successfully for replacement therapy in Mucopolysaccharidosis VI, it may be useful to restore ARSB activity to normal levels and increase degradation of sulfated GAGs in CF patients. PMID:22550062

  5. DNA end joining activity is reduced in Alzheimer's disease.

    PubMed

    Shackelford, Deborah A

    2006-04-01

    Evidence indicates that oxidative stress-induced damage to DNA, protein, and other cellular components contributes to the progression of Alzheimer's disease (AD). Several studies indicate that postmitotic neurons have a reduced capacity for some types of DNA repair, which is further compromised by aging. Thus in AD, the cellular response to increased oxidative DNA damage may be inadequate to protect the genome. Mammalian cells use several mechanisms to repair DNA damage generated during normal oxidative metabolism or by genotoxic insults. The predominant mechanism to repair double strand breaks is non-homologous end joining (NHEJ) which utilizes the DNA-dependent protein kinase (DNA-PK) complex. A cell-free DNA end joining assay was employed to determine if NHEJ was reduced in nuclear cortical extracts from brains of AD versus normal subjects. This report demonstrates that end joining activity and protein levels of DNA-PK catalytic subunit are significantly lower in AD brains compared to normal controls. The amount of end joining activity correlates with the expression of DNA-PK and is dependent on DNA-PK catalytic activity. This indicates that repair of DNA double-strand breaks by the DNA-PK-dependent NHEJ pathway may be deficient in AD.

  6. Serum thymus and activation-regulated chemokine level monitoring may predict disease relapse detected by PET scan after reduced-intensity allogeneic stem cell transplantation in patients with Hodgkin lymphoma.

    PubMed

    Farina, Lucia; Rezzonico, Francesca; Spina, Francesco; Dodero, Anna; Mazzocchi, Arabella; Crippa, Flavio; Alessi, Alessandra; Dalto, Serena; Viviani, Simonetta; Corradini, Paolo

    2014-12-01

    Patients with relapsed and refractory Hodgkin lymphoma (HL) may experience long-term survival after allogeneic stem cell transplantation (alloSCT), but disease recurrence represents the main cause of treatment failure. Positron-emission tomography (PET)-positive patients after alloSCT have a dismal outcome. Serum thymus and activation-regulated chemokine (TARC) is produced by Reed-Sternberg cells and may be a marker of disease. Our study aimed at assessing whether TARC levels after alloSCT correlated with disease status and whether TARC monitoring could increase the ability to predict relapse. Twenty-four patients were evaluated in a prospective observational study. TARC serum level and PET were assessed before and after alloSCT during the follow-up (median, 30 months; range, 2 to 54). Before alloSCT, the median TARC level was 721 pg/mL (range, 209 to 1332) in PET-negative patients and 2542 pg/mL (range, 94 to 13,870) in PET-positive patients. After alloSCT, TARC was 620 pg/mL (range, 12 to 4333) in persistently PET-negative patients compared with 22,397 pg/mL (range, 602 to 106,578) in PET-positive patients (P < .0001). In 7 patients who relapsed after alloSCT, TARC level increased progressively even before PET became positive, with a median fold increase of 3.19 (range, 1.66 to 7.11) at relapse. The cut-off value of 1726 pg/mL had a sensitivity of 100% and a specificity of 71% for PET positivity. Patients with at least 1 TARC value above 1726 pg/mL during the first year after alloSCT had a worse progression-free survival (P = .031). In conclusion, TARC was correlated with disease status and its monitoring may be able to predict PET positivity after alloSCT, thus potentially allowing an early immune manipulation.

  7. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

    PubMed Central

    Sung, Nak Yoon

    2015-01-01

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

  8. Reduced ING1 levels in breast cancer promotes metastasis

    PubMed Central

    Chen, Jie; Tran, Uyen; Yang, Yang; Salazar, Carolina; Magliocco, Anthony; Klimowicz, Alexander; Jirik, Frank R.; Riabowol, Karl

    2014-01-01

    INhibitor of Growth 1 (ING1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. ING1 levels were quantified in >500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering ING levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. ING1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in ER- or Her2+ patients. In these patients ING1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by ING1 was breast cancer (p = 0.0008). Decreasing levels of ING1 increased, and increasing levels decreased, migration and invasion of MDA-MB231 cells in vitro. ING1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that ING1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that ING1 may have a therapeutic role for inhibiting metastasis of breast cancer. PMID:24962136

  9. LLMapReduce: Multi-Level Map-Reduce for High Performance Data Analysis

    DTIC Science & Technology

    2016-05-23

    Lexington, MA, U.S.A Abstract— The map-reduce parallel programming model has become extremely popular in the big data community. Many big data ...to big data users running on a supercomputer. LLMapReduce dramatically simplifies map-reduce programming by providing simple parallel programming...SLURM; LSF I. INTRODUCTION Large scale computing is currently dominated by four ecosystems: supercomputing, database, enterprise, and big data [1

  10. Techniques for Reducing Gun Blast Noise Levels: An Experimental Study

    DTIC Science & Technology

    1981-04-01

    gun muzzle blast noise level were in- vestigated experimentally to determine potential effectiveness and utility for existing major-caliber guns...impact on training and testing operations was to be minimized. Most of the noise reduction techniques that were investigated involve the use of some type ...shock noise level at the earth’s surface varies according to a complicated dependence upon projectile trajectory, projectile speed along the trajectory

  11. Reduced-activation steels: Future development for improved creep strength

    NASA Astrophysics Data System (ADS)

    Klueh, R. L.

    2008-08-01

    Reduced-activation steels for fusion applications were developed in the 1980s to replace the elevated-temperature commercial steels first considered. The new steels were patterned after the commercial steels, with the objective that the new steels have yield stress and ultimate tensile strength and impact toughness in a Charpy test comparable to or better than the steels they replaced. That objective was achieved in reduced-activation steels developed in Japan, Europe, and the United States. Although tensile and impact toughness of the reduced-activation steels exceed those of the commercial steels they were patterned after, their creep-rupture properties are inferior to some commercial steels they replaced. They are even more inferior to commercial steels developed since the 1980s. In this paper, compositional differences between reduced-activation steels and new commercial steels are examined, and compositions are proposed for development of new-and-improved reduced-activation steels.

  12. Identification of Dihydropyridines That Reduce Cellular Tau Levels

    PubMed Central

    Evans, Christopher G.; Jinwal, Umesh K.; Makley, Leah N.

    2011-01-01

    A series of dihydropyridines were identified that have an effect on the accumulation of tau, an important target in Alzheimer's disease. The dihydropyridine collection was expanded using the Hantzsch multicomponent reaction to develop preliminary structure-activity relationships. PMID:21082080

  13. Identification of dihydropyridines that reduce cellular tau levels.

    PubMed

    Evans, Christopher G; Jinwal, Umesh K; Makley, Leah N; Dickey, Chad A; Gestwicki, Jason E

    2011-01-07

    A series of dihydropyridines were identified that have an effect on the accumulation of tau, an important target in Alzheimer's disease. The dihydropyridine collection was expanded using the Hantzsch multicomponent reaction to develop preliminary structure-activity relationships.

  14. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

    PubMed

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

  15. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice*

    PubMed Central

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice. PMID:25559957

  16. Physical activity level, waist circumference, and mortality

    PubMed Central

    Staiano, Amanda E.; Reeder, Bruce A.; Elliott, Susan; Joffres, Michel R.; Pahwa, Punam; Kirkland, Susan A.; Paradis, Gilles; Katzmarzyk, Peter T.

    2014-01-01

    This study predicted all-cause mortality based on physical activity level (active or inactive) and waist circumference (WC) in 8208 Canadian adults in Alberta, Manitoba, Nova Scotia, and Saskatchewan, surveyed between 1986–1995 and followed through 2004. Physically inactive adults had higher mortality risk than active adults overall (hazard ratio, 95% confidence interval = 1.20, 1.05–1.37) and within the low WC category (1.51, 1.19–1.92). Detrimental effects of physical inactivity and high WC demonstrate the need for physical activity promotion. PMID:22703160

  17. Dissociating speech perception and comprehension at reduced levels of awareness.

    PubMed

    Davis, Matthew H; Coleman, Martin R; Absalom, Anthony R; Rodd, Jennifer M; Johnsrude, Ingrid S; Matta, Basil F; Owen, Adrian M; Menon, David K

    2007-10-09

    We used functional MRI and the anesthetic agent propofol to assess the relationship among neural responses to speech, successful comprehension, and conscious awareness. Volunteers were scanned while listening to sentences containing ambiguous words, matched sentences without ambiguous words, and signal-correlated noise (SCN). During three scanning sessions, participants were nonsedated (awake), lightly sedated (a slowed response to conversation), and deeply sedated (no conversational response, rousable by loud command). Bilateral temporal-lobe responses for sentences compared with signal-correlated noise were observed at all three levels of sedation, although prefrontal and premotor responses to speech were absent at the deepest level of sedation. Additional inferior frontal and posterior temporal responses to ambiguous sentences provide a neural correlate of semantic processes critical for comprehending sentences containing ambiguous words. However, this additional response was absent during light sedation, suggesting a marked impairment of sentence comprehension. A significant decline in postscan recognition memory for sentences also suggests that sedation impaired encoding of sentences into memory, with left inferior frontal and temporal lobe responses during light sedation predicting subsequent recognition memory. These findings suggest a graded degradation of cognitive function in response to sedation such that "higher-level" semantic and mnemonic processes can be impaired at relatively low levels of sedation, whereas perceptual processing of speech remains resilient even during deep sedation. These results have important implications for understanding the relationship between speech comprehension and awareness in the healthy brain in patients receiving sedation and in patients with disorders of consciousness.

  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. 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…

  20. Maintaining reduced noise levels in a resource-constrained neonatal intensive care unit by operant conditioning.

    PubMed

    Ramesh, A; Denzil, S B; Linda, R; Josephine, P K; Nagapoornima, M; Suman Rao, P N; Swarna Rekha, A

    2013-03-01

    To evaluate the efficacy of operant conditioning in sustaining reduced noise levels in the neonatal intensive care unit (NICU). Quasi-experimental study on quality of care. Level III NICU of a teaching hospital in south India. 26 staff employed in the NICU. (7 Doctors, 13 Nursing staff and 6 Nursing assistants). Operant conditioning of staff activity for 6 months. This method involves positive and negative reinforcement to condition the staff to modify noise generating activities. Comparing noise levels in decibel: A weighted [dB (A)] before conditioning with levels at 18 and 24 months after conditioning. Decibel: A weighted accounts for noise that is audible to human ears. Operant conditioning for 6 months sustains the reduced noise levels to within 62 dB in ventilator room 95% CI: 60.4 - 62.2 and isolation room (95% CI: 55.8 - 61.5). In the preterm room, noise can be maintained within 52 dB (95% CI: 50.8 - 52.6). This effect is statistically significant in all the rooms at 18 months (P = 0.001). At 24 months post conditioning there is a significant rebound of noise levels by 8.6, 6.7 and 9.9 dB in the ventilator, isolation and preterm room, respectively (P =0.001). Operant conditioning for 6 months was effective in sustaining reduced noise levels. At 18 months post conditioning, the noise levels were maintained within 62 dB (A), 60 dB (A) and 52 dB (A) in the ventilator, isolation and pre-term room, respectively. Conditioning needs to be repeated at 12 months in the ventilator room and at 18 months in the other rooms.

  1. Promoter-proximal polyadenylation sites reduce transcription activity

    PubMed Central

    Andersen, Pia K.; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500 base pairs of the promoter. In contrast, promoter-proximal positioning of a pA site-independent histone gene terminator supports high transcription levels. We propose that optimal communication between a pA site-dependent gene terminator and its promoter critically depends on gene length and that short RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels. PMID:23028143

  2. 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.

  3. Dissociating speech perception and comprehension at reduced levels of awareness

    PubMed Central

    Davis, Matthew H.; Coleman, Martin R.; Absalom, Anthony R.; Rodd, Jennifer M.; Johnsrude, Ingrid S.; Matta, Basil F.; Owen, Adrian M.; Menon, David K.

    2007-01-01

    We used functional MRI and the anesthetic agent propofol to assess the relationship among neural responses to speech, successful comprehension, and conscious awareness. Volunteers were scanned while listening to sentences containing ambiguous words, matched sentences without ambiguous words, and signal-correlated noise (SCN). During three scanning sessions, participants were nonsedated (awake), lightly sedated (a slowed response to conversation), and deeply sedated (no conversational response, rousable by loud command). Bilateral temporal-lobe responses for sentences compared with signal-correlated noise were observed at all three levels of sedation, although prefrontal and premotor responses to speech were absent at the deepest level of sedation. Additional inferior frontal and posterior temporal responses to ambiguous sentences provide a neural correlate of semantic processes critical for comprehending sentences containing ambiguous words. However, this additional response was absent during light sedation, suggesting a marked impairment of sentence comprehension. A significant decline in postscan recognition memory for sentences also suggests that sedation impaired encoding of sentences into memory, with left inferior frontal and temporal lobe responses during light sedation predicting subsequent recognition memory. These findings suggest a graded degradation of cognitive function in response to sedation such that “higher-level” semantic and mnemonic processes can be impaired at relatively low levels of sedation, whereas perceptual processing of speech remains resilient even during deep sedation. These results have important implications for understanding the relationship between speech comprehension and awareness in the healthy brain in patients receiving sedation and in patients with disorders of consciousness. PMID:17938125

  4. [Oral or trandsdermanl hormone replacement therapy reduces interleukine-6 levels].

    PubMed

    Saucedo García, Renata; Basurto Acevedo, Lourdes; Rico Rosillo, Guadalupe; Galván, Rosa E; Zárate Treviño, Arturo

    2006-03-01

    To compare the effect of oral and transdermal estrogen replacement therapy (ET) on circulating interleukin-6 (IL-6) in post-menopausal women. Prospective open trial study in 55 healthy hysterectomized postmenopausal women with a mean age of 52 years. Twenty-seven women received oral conjugated equine estrogens (0.625 mg daily) and the remaining 28 received transdermal estrogen replacement therapy (50 microg/day) during 6 months. At baseline both groups were similar as to age, body weight, and body mass index as well as serum levels of LH, FSH, 17-beta estradiol (E2) and IL-6. Baseline elevated IL-6 levels decreased significantly (p<0.05) after both oral and transdermal estrogen replacement therapy; this decrement showed no difference between the two groups. After the follow-up there were no differences in body weight and body mass index between groups; however, in the oral group there was a trend to increment this parameters. Serum levels of E2 and IL-6 were negatively correlated in the two groups and IL-6 was positively correlated with body mass index in untreated women and this correlation was the same in women with estrogen replacement therapy. The decrement of IL-6 after estrogen replacement therapy was similar for both routes of administration; in addition IL-6 had a negative correlation with E2 and a positive correlation with body mass index.

  5. [Subliminal perception and the levels of activation].

    PubMed

    Borgeat, F; Chabot, R; Chaloult, L

    1981-06-01

    The influence of the auditory subliminal messages on the level of activation has been evaluated through a double-blind study. Twenty consenting subjects were alternately submitted to activating and deactivating subliminal messages. Activation changes were estimated through the variations in the scores at the Mood Adjective Check List. Five out of this test's six factors concerned by the content of the subliminal messages responded differently according to the nature of these messages; four factors did so to a statistically significant degree. These results tend to indicate that auditory subliminal perceptions can influence the level of activation. The authors raise several questions, especially stressing that the parameters regulating subliminal response and susceptibility remain largely undefined and in need of systematic investigation.

  6. 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. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. Locomotor activity and tissue levels following acute ...

    EPA Pesticide Factsheets

    Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administ

  9. 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.

  10. Neck Muscle Activation Levels During Frontal Impacts

    DTIC Science & Technology

    2004-09-01

    right and left upper trapezius and sternocleidomastoid . Amplitude and frequency components of the signals were evaluated to determine the amount of...Gx acceleration levels. The trapezius produced more force than the sternocleidomastoid . Activity of both muscle groups was synchronized, by their...dynamic environment. The role of upper trapezius and sternocleidomastoid (SCM) during long-duration head and neck loading situations has been

  11. Recreational Activities to Reduce Behavioural Symptoms in Dementia

    PubMed Central

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

    2009-01-01

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

  12. 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

  13. Reduced Switching Frequency Active Harmonic Elimination for Multilevel Converters

    SciTech Connect

    Du, Zhong; Tolbert, Leon M; Chiasson, John N; Ozpineci, Burak

    2008-01-01

    This paper presents a reduced switching-frequency active-harmonic-elimination method (RAHEM) to eliminate any number of specific order harmonics of multilevel converters. First, resultant theory is applied to transcendental equations to eliminate low-order harmonics and to determine switching angles for a fundamental frequency-switching scheme. Next, based on the number of harmonics to be eliminated, Newton climbing method is applied to transcendental equations to eliminate high-order harmonics and to determine switching angles for the fundamental frequency-switching scheme. Third, the magnitudes and phases of the residual lower order harmonics are computed, generated, and subtracted from the original voltage waveform to eliminate these low-order harmonics. Compared to the active-harmonic-elimination method (AHEM), which generates square waves to cancel high-order harmonics, RAHEM has lower switching frequency. The simulation results show that the method can effectively eliminate all the specific harmonics, and a low total harmonic distortion (THD) near sine wave is produced. An experimental 11-level H-bridge multilevel converter with a field-programmable gate-array controller is employed to experimentally validate the method. The experimental results show that RAHEM does effectively eliminate any number of specific harmonics, and the output voltage waveform has low switching frequency and low THD.

  14. Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

    PubMed

    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.

  15. Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes

    PubMed Central

    SIVILS, JEFFREY C.; GONZALEZ, IVEN; BAIN, LISA J.

    2010-01-01

    The multidrug resistance-associated protein 1 (MRP1/ABCC1) is a member of the ABC active transporter family that can transport several steroid hormone conjugates, including 17β-estradiol glucuronide, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate. The present study investigated the role that MRP1 plays in maintaining proper hormone levels in the serum and testes. Serum and testicular steroid hormone levels were examined in both wild-type mice and Mrp1 null mice. Serum testosterone levels were reduced 5-fold in mice lacking Mrp1, while testicular androstenedione, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were significantly reduced by 1.7- to 4.5-fold in Mrp1 knockout mice. Investigating the mechanisms responsible for the reduction in steroid hormones in Mrp1-/- mice revealed no differences in the expression or activity of enzymes that inactivate steroids, the sulfotransferases or glucuronosyltransferases. However, steroid biosynthetic enzyme levels in the testes were altered. Cyp17 protein levels were increased by 1.6-fold, while Cyp17 activity using progesterone as a substrate was also increased by 1.4-2.0-fold in mice lacking Mrp1. Additionally, the ratio of 17β-hydroxysteroid dehydrogenase to 3β-hydroxysteroid dehydrogenase, and steroidogenic factor 1 to 3βhydroxysteroid dehydrogenase were significantly increased in the testes of Mrp1-/- mice. These results indicate that Mrp1-/- mice have lowered steroid hormones levels, and suggests that upregulation of steroid biosynthetic enzymes may be an attempt to maintain proper steroid hormone homeostasis. PMID:20178799

  16. The impact of pregnancy on physical activity level.

    PubMed

    Fell, Deshayne B; Joseph, K S; Armson, B Anthony; Dodds, Linda

    2009-09-01

    The purpose of this study was to compare women's levels of physical activity during early pregnancy and during the year before pregnancy, and to identify characteristics associated with discontinuing sports and exercise among women previously active during the year before pregnancy. Data collected from 1,737 women enrolled in a prospective cohort study and who had no contraindications for exercise were included in this analysis. Measures of physical activity (including household and care-giving activities, active living and sports and exercise activities) during early pregnancy were compared to the year before pregnancy. Log binomial regression was used to identify factors associated with discontinuing sports and exercise during pregnancy. There was a statistically significant decrease in all summary measures of physical activity during early pregnancy. The largest decreases were observed in sports and exercise activity. Among women active before pregnancy, age <35 years, multiparity, less than university education, pre-pregnancy body mass index (BMI) > or = 30 kg/m(2) and lower levels of pre-pregnancy exercise were associated with discontinuing sports and exercise activities during pregnancy. Most women reduced their physical activity level during the first 20 weeks of pregnancy compared with their level of activity during the year prior to pregnancy, particularly for sports and exercise, although a small proportion of women in this study actually increased their activity in this area during early pregnancy. Participation in sports and exercise activity during pregnancy is potentially modifiable and could favorably impact perinatal health and maternal post-partum weight. The results of this study suggests that pregnancy is an event that leads to a decrease in physical activity.

  17. 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.

  18. Effortful Retrieval Reduces Hippocampal Activity and Impairs Incidental Encoding

    PubMed Central

    Reas, Emilie T.; Brewer, James B.

    2014-01-01

    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

  19. Very low activated factor VII and reduced factor VII antigen in familial abetalipoproteinaemia.

    PubMed

    Miller, G J; Mitropoulos, K A; Nanjee, M N; Howarth, D J; Martin, J C; Esnouf, M P; Reeves, B E; Miller, N E; Cooper, J A

    1998-08-01

    Abetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyceride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 micromol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients' mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

  20. Fermented soy permeate reduces cytokine level and oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Malardé, Ludivine; Groussard, Carole; Lefeuvre-Orfila, Luz; Vincent, Sophie; Efstathiou, Théo; Gratas-Delamarche, Arlette

    2015-01-01

    Oxidative stress and inflammation are involved in the development of type 1 diabetes and its complications. Because two compounds found in soy, that is, isoflavones and alpha-galactooligosaccharides, have been shown to exert antioxidant and anti-inflammatory effects, this study aimed to assess the effects of a dietary supplement containing these two active compounds, the fermented soy permeate (FSP). We hypothesized that FSP would be able to reduce in vivo oxidative stress and inflammation in streptozotocin (STZ)-induced type 1 diabetic rats. Thirty male Wistar rats were divided into the control placebo, diabetic placebo, and diabetic FSP-supplemented groups. They received daily, by oral gavage, water (placebo groups) or diluted FSP (0.1 g/day; FSP-supplemented group). After 3 weeks, glycemic regulation (glycemia and fructosamine level); the plasma level of carboxymethyllysine (CML), a marker of systemic oxidative stress in diabetes; and the plasma levels of inflammatory markers (CRP, IL-1β, IL-6, and uric acid) were evaluated. Markers of oxidative damage (isoprostanes and GSH/GSSG), antioxidant enzymatic activity (SOD and GPX), and Mn-SOD content were determined in skeletal muscle (gastrocnemius). Diabetic placebo rats exhibited higher CML levels, lower SOD and GPX activities, and decreased Mn-SOD contents. FSP supplementation in diabetic animals normalized the CML and antioxidant enzymatic activity levels and tended to increase Mn-SOD expression. The markers of inflammation whose levels were increased in the diabetic placebo group were markedly decreased by FSP (IL-1β: -75%, IL-6: -46%, and uric acid: -17%), except for CRP. Our results demonstrate that FSP exhibited antioxidant and anti-inflammatory properties in vivo in STZ-induced diabetic rats.

  1. Is it possible to reduce the knee joint compression force during level walking with hiking poles?

    PubMed

    Jensen, S B; Henriksen, M; Aaboe, J; Hansen, L; Simonsen, E B; Alkjaer, T

    2011-12-01

    Walking with hiking poles has become a popular way of exercising. Walking with poles is advocated as a physical activity that significantly reduces the loading of the hip, knee and ankle joints. We have previously observed that pole walking does not lead to a reduction of the load on the knee joint. However, it is unclear whether an increased force transmitted through the poles can reduce the load on the knee joint. Thus, the purpose of the present study was to investigate if an increased load transmitted through the arms to the poles could reduce the knee joint compression force during level walking with poles. We hypothesized that an increased pole force would result in a reduction of the knee joint compression force. Gait analyses from 10 healthy subjects walking with poles were obtained. The pole force was measured simultaneously during the gait analyses. The knee joint compression forces were estimated by using a biomechanical knee joint model. The results showed that the subjects were able to increase the pole force by 2.4 times the normal pole force. However, this did not lead to a reduction in the knee joint compressive force and we rejected our hypothesis. In conclusion, the use of poles during level walking does not seem to reduce knee joint compressive loads. However, it is possible that the use of poles in other populations (e.g. osteoarthritis patients) and in terrain would unload the knee joint. This should be investigated in the future.

  2. Hydrogen gas alleviates oxygen toxicity by reducing hydroxyl radical levels in PC12 cells

    PubMed Central

    Yu, Junchao; Yu, Qiuhong; Liu, Yaling; Zhang, Ruiyun; Xue, Lianbi

    2017-01-01

    Hyperbaric oxygen (HBO) therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA) is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS), breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H2) can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H2 on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H2 on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H2 at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H2 promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O2•-, H2O2, or NO• in PC12 cells during HBO therapy. These results indicated that H2 effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H2 could be potentially used as an antioxidant during HBO therapy. PMID:28362819

  3. Hydrogen gas alleviates oxygen toxicity by reducing hydroxyl radical levels in PC12 cells.

    PubMed

    Yu, Junchao; Yu, Qiuhong; Liu, Yaling; Zhang, Ruiyun; Xue, Lianbi

    2017-01-01

    Hyperbaric oxygen (HBO) therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA) is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS), breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H2) can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H2 on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H2 on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H2 at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H2 promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O2•-, H2O2, or NO• in PC12 cells during HBO therapy. These results indicated that H2 effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H2 could be potentially used as an antioxidant during HBO therapy.

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

    PubMed

    Lee, Younhee; Joo, Nami

    2016-04-01

    The purpose of this study was to find out the level of knowledge on sugar-related nutrition among mothers with preschool children. 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. 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. 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.

  5. Study of Using Excess Stock to Reduce Naval Aviation Depot-Level Repairable Piece Part Backorders

    DTIC Science & Technology

    2016-12-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA MBA PROFESSIONAL REPORT STUDY OF USING EXCESS STOCK TO REDUCE NAVAL AVIATION... STUDY OF USING EXCESS STOCK TO REDUCE NAVAL AVIATION DEPOT-LEVEL REPAIRABLE PIECE PART BACKORDERS 5. FUNDING NUMBERS 6. AUTHOR(S) Jennifer L...unlimited. STUDY OF USING EXCESS STOCK TO REDUCE NAVAL AVIATION DEPOT-LEVEL REPAIRABLE PIECE PART BACKORDERS Jennifer L. Custard, Lieutenant

  6. 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

  7. 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.

  8. Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia.

    PubMed

    Hofherr, Sean E; Mok, Hoyin; Gushiken, Francisca C; Lopez, Jose A; Barry, Michael A

    2007-09-01

    Thrombocytopenia is one of the complications for in vivo administration of adenovirus serotype 5 (Ad5) vectors after intravenous injection. In this paper, we investigated the mechanism of Ad5-induced thrombocytopenia and how these effects are attenuated by polyethylene glycol (PEG) modification of Ad5 (Ad-PEG). After intravenous injection, accelerated platelet loss was observed in Ad-injected mice but not in their Ad-PEG-injected counterparts. This platelet loss induced by Ad5 corresponded with increases in coagulation D-dimer levels, splenomegaly, and, later, production of megakaryocytes in the bone marrow. In contrast, these responses were blunted or ablated after injection of Ad-PEG. Ad5 activated both platelets and endothelial cells directly in vitro as evidenced by induction of P-selectin and the formation of von Willebrand factor-platelet strings and in vivo as evidenced by the induction of E-selectin messenger RNA. PEGylation blunted these observed activations. These data suggest that Ad5 may induce thrombocytopenia by direct activation of endothelial cells in addition to its direct effects on platelets. This link provides an important clue for the understanding of the mechanisms of thrombocytopenia associated with Ad5. Given that PEGylation blunted interactions of Ad with platelets and endothelial cells, reduced D-dimer formation, reduced thrombocytopenia, and reduced splenomegaly, these data suggest that this simple vector modification may have utility to improve the safety of Ad vectors for human gene therapy.

  9. CAV1 siRNA Reduces Membrane Estrogen Receptor-α Levels and Attenuates Sexual Receptivity

    PubMed Central

    Christensen, Amy

    2012-01-01

    Although classic estrogen receptors (ER) have been proposed to mediate estradiol signaling, it has been relatively recently that mechanisms of trafficking these receptors have been elucidated. ERα is palmitoylated and associates with caveolin proteins to be targeted to the cell membrane. Caveolins are scaffold proteins that not only traffic ERα to the membrane but also are involved in establishing metabotropic glutamate receptor interactions that are necessary for activating G protein signaling. To demonstrate the role of caveolin proteins in regulating an estradiol-dependent behavior, sexual receptivity, we used small interfering RNA to knock down caveolin-1 (CAV1) expression in the arcuate nucleus of the hypothalamus. In CAV1 knockdown rats, membrane, but not intracellular levels of ERα, were significantly reduced. As expected, estrogenic stimulation of the arcuate nucleus of the hypothalamus to medial preoptic nucleus projection was abrogated in CAV1 knockdown rats, indicating that the membrane-initiated activation of this circuit was compromised. Moreover, estradiol-induced lordosis behavior that is dependent on activation of μ-opioid receptors in the medial preoptic nucleus was also significantly reduced. Thus, CAV1-mediated ERα trafficking to the cell membrane is required for estradiol activation of circuits underlying female sexual receptivity. PMID:22669893

  10. 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.

  11. Azilsartan is associated with increased circulating angiotensin-(1-7) levels and reduced renovascular 20-HETE levels.

    PubMed

    Carroll, Mairéad A; Kang, YounJung; Chander, Praveen N; Stier, Charles T

    2015-05-01

    Activation of angiotensin (ANG) II type 1 receptors (AT1R) promotes vasoconstriction, inflammation, and renal dysfunction. In this study, we addressed the ability of azilsartan (AZL), a new AT1R antagonist, to modulate levels of plasma ANG-(1-7) and renal epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE). Sprague-Dawley rats were infused with ANG II (125 ng/min) or vehicle (VEH). AZL (3 mg/kg/day) or VEH was administered starting 1 day prior to ANG II or VEH infusion. On day 10, plasma was obtained for measurement of ANG-(1-7) and kidneys for isolation of microvessels for EET and 20-HETE determination and histological evaluation. Mean 24-hour blood pressure (BP) was not different between VEH and AZL treatment groups, whereas the BP elevation with ANG II infusion (121 ± 5 mm Hg) was completely normalized with AZL cotreatment (86 ± 3 mm Hg). The ANG II-induced renal damage was attenuated and cardiac hypertrophy prevented with AZL cotreatment. Plasma ANG-(1-7) levels (pg/ml) were increased with AZL treatment (219 ± 22) and AZL + ANG II infusion (264 ± 93) compared to VEH controls (74.62 ± 8). AZL treatment increased the ratio of EETs to their dihydroxyeicosatrienoic acid (DHET) metabolites and reduced 20-HETE levels. Treatment with AZL completely antagonized the elevation of BP induced by ANG II, prevented cardiac hypertrophy, attenuated renal damage, and increased ANG-(1-7) and EET/DHET ratio while diminishing 20-HETE levels. Increased ANG-(1-7) and EETs levels may emerge as novel therapeutic mechanisms contributing to the antihypertensive and antihypertrophic actions of AZL treatment and their relative role compared to AT1R blockade may depend on the etiology of the hypertension. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. 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,…

  13. Salmonella in chicken: current and developing strategies to reduce contamination at farm level.

    PubMed

    Vandeplas, S; Dubois Dauphin, R; Beckers, Y; Thonart, P; Théwis, A

    2010-04-01

    Salmonella is a human pathogen that frequently infects poultry flocks. Consumption of raw or undercooked contaminated poultry products can induce acute gastroenteritis in humans. Faced with the public health concerns associated with salmonellosis, the European Union has established a European regulation forcing member states to implement control programs aimed at reducing Salmonella prevalence in poultry production, especially at the primary production level. The purpose of the present review article is to summarize the current research and to suggest future developments in the area of Salmonella control in poultry, which may be of value to the industry in the coming years. The review will focus especially on preventive strategies that have been developed and that aim at reducing the incidence of Salmonella colonization in broiler chickens at the farm level. In addition to the usual preventive hygienic measures, other strategies have been investigated, such as feed and drinking water acidification with organic acids and immune strategies based on passive and active immunity. Modification of the diet by changing ingredients and nutrient composition with the intent of reducing a bird's susceptibility to Salmonella infection also has been examined. Because in ovo feeding accelerates small intestine development and enhances epithelial cell function, this approach could be an efficient tool for controlling enteric pathogens. Feed additives such as antibiotics, prebiotics, probiotics, and synbiotics that modify the intestinal microflora are part of another field of investigation, and their success depends on the additive used. Other control methods such as the use of chlorate products and bacteriophages also are under study.

  14. Enterovirus 71 Disrupts Interferon Signaling by Reducing the Level of Interferon Receptor 1

    PubMed Central

    Lu, Jing; Yi, Lina; Zhao, Jin; Yu, Jun; Chen, Ying; Lin, Marie C.; Kung, Hsiang-Fu

    2012-01-01

    The recent outbreak of enterovirus 71 (EV71) infected millions of children and caused over 1,000 deaths. To date, neither an effective vaccine nor antiviral treatment is available for EV71 infection. Interferons (IFNs) have been successfully applied to treat patients with hepatitis B and C viral infections for decades but have failed to treat EV71 infections. Here, we provide the evidence that EV71 antagonizes type I IFN signaling by reducing the level of interferon receptor 1 (IFNAR1). We show that the host cells could sense EV71 infection and stimulate IFN-β production. However, the induction of downstream IFN-stimulated genes is inhibited by EV71. Also, only a slight interferon response and antiviral effects could be detected in cells treated with recombinant type I IFNs after EV71 infection. Further studies reveal that EV71 blocks the IFN-mediated phosphorylation of STAT1, STAT2, Jak1, and Tyk2 by reducing IFNAR1. Finally, we identified the 2A protease encoded by EV71 as an antagonist of IFNs and show that the protease activity is required for reducing IFNAR1 levels. Taken together, our study for the first time uncovers a mechanism used by EV71 to antagonize type I IFN signaling and provides new targets for future antiviral strategies. PMID:22258259

  15. Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies.

    PubMed

    Barrachina, Marta; Castaño, Esther; Dalfó, Esther; Maes, Tamara; Buesa, Carlos; Ferrer, Isidro

    2006-05-01

    Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein and ubiquitin in protein aggregates conforming Lewy bodies and Lewy neurites. Ubiquitin C-terminal hydrolase-1 (UCHL-1) disassembles polyubiquitin chains to increase the availability of free monomeric ubiquitin to the ubiquitin proteasome system (UPS) thus favoring protein degradation. Since mutations in the UCHL-1 gene, reducing UPS activity by 50%, have been reported in autosomal dominant PD, and UCHL-1 inhibition results in the formation of alpha-synuclein aggregates in mesencephalic cultured neurons, the present study was initiated to test UCHL-1 mRNA and protein levels in post-mortem frontal cortex (area 8) of PD and DLB cases, compared with age-matched controls. TaqMan PCR assays, and Western blots demonstrated down-regulation of UCHL-1 mRNA and UCHL-1 protein in the cerebral cortex in DLB (either in pure forms, not associated with Alzheimer disease: AD, and in common forms, with accompanying AD changes), but not in PD, when compared with age-matched controls. Interestingly, UCHL-1 mRNA and protein expressions were reduced in the medulla oblongata in the same PD cases. Moreover, UCHL-1 protein was decreased in the substantia nigra in cases with Lewy body pathology. UCHL-1 down-regulation was not associated with reduced protein levels of several proteasomal subunits, including 20SX, 20SY, 19S and 11Salpha. Yet UCHL-3 expression was reduced in the cerebral cortex of PD and DLB patients. Together, these observations show reduced UCHL-1 expression as a contributory factor in the abnormal protein aggregation in DLB, and points UCHL-1 as a putative therapeutic target in the treatment of DLB.

  16. Can Graduated Compressive Stockings Reduce Muscle Activity during Running?

    ERIC Educational Resources Information Center

    Lucas-Cuevas, Ángel Gabriel; Priego Quesada, José Ignacio; Giménez, José Vicente; Aparicio, Inmaculada; Cortell-Tormo, Juan Manuel; Pérez-Soriano, Pedro

    2017-01-01

    Purpose: Graduated compressive stockings (GCS) have been suggested to influence performance by reducing muscle oscillations and improving muscle function and efficiency. However, no study to date has analyzed the influence of GCS on muscle activity during running. The objective of the study was to analyze the influence of GCS on the perception of…

  17. Activity of sulfate-reducing bacteria under simulated reservoir conditions

    SciTech Connect

    Rosnes, J.T.; Graue, A.; Lien, T. )

    1991-05-01

    This paper reports on sulfate-reducing bacteria (SRB) that have been isolated from hot oilfield waters from subsea oil reservoirs in the North Sea. Experiments with these bacteria in a reservoir simulator indicate that SRB may maintain their activity in the conditions found in most North Sea reservoirs and, if precautions are not taken, may contribute to souring of the oil and gas.

  18. A reduced energy supply strategy in active vibration control

    NASA Astrophysics Data System (ADS)

    Ichchou, M. N.; Loukil, T.; Bareille, O.; Chamberland, G.; Qiu, J.

    2011-12-01

    In this paper, a control strategy is presented and numerically tested. This strategy aims to achieve the potential performance of fully active systems with a reduced energy supply. These energy needs are expected to be comparable to the power demands of semi-active systems, while system performance is intended to be comparable to that of a fully active configuration. The underlying strategy is called 'global semi-active control'. This control approach results from an energy investigation based on management of the optimal control process. Energy management encompasses storage and convenient restitution. The proposed strategy monitors a given active law without any external energy supply by considering purely dissipative and energy-demanding phases. Such a control law is offered here along with an analysis of its properties. A suboptimal form, well adapted for practical implementation steps, is also given. Moreover, a number of numerical experiments are proposed in order to validate test findings.

  19. Cost of reducing aromatics and sulfur levels in motor-vehicle fuels. Volume 2. Final report

    SciTech Connect

    Felten, J.R.; McCarthy, K.M.

    1988-08-01

    Linear-programming (LP) models were developed for five refineries representative of the California refining industry and validated against historic operation. Process options to reduce gasoline and diesel contaminants were selected and represented in the LP models. Costs were estimated to separately reduce aromatics levels in automotive gasoline, aromatics in diesel, and sulfur in diesel for 1991 and 1995. Cost impacts were scaled up to obtain the overall cost impact in California. Estimates were made of total aromatics and benzene levels in gasoline and of sulfur, aromatics, and cetane levels in diesel. Estimates were made of the impact on refinery emissions, automotive emissions, and automotive performance. The cost to reduce diesel sulfur level to .05% was 6.3 cents/gallon. The cost to reduce diesel aromatics level to 10% was 27.6 cents/gallon. The cost to reduce gasoline aromatics levels by 18% was 7.0 cents/gallon.

  20. Activation of the AMP-activated protein kinase reduces inflammatory nociception.

    PubMed

    Russe, Otto Quintus; Möser, Christine V; Kynast, Katharina L; King, Tanya S; Stephan, Heike; Geisslinger, Gerd; Niederberger, Ellen

    2013-11-01

    The activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) has been associated with beneficial effects such as improvement of hyperglycemic states in diabetes as well as reduction of obesity and inflammatory processes. Recent studies provide evidence for a further role of AMPK in models of acute and neuropathic pain. In this study, we investigated the impact of AMPK on inflammatory nociception. Using 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin as AMPK activators, we observed anti-inflammatory and antinociceptive effects in 2 models of inflammatory nociception. The effects were similar to those observed with the standard analgesic ibuprofen. The mechanism appears to be based on regulation of the AMPKα2 subunit of the kinase because AMPKα2 knockout mice showed increased nociceptive responses that could not be reversed by the AMPK activators. On the molecular level, antinociceptive effects are at least partially mediated by reduced activation of different MAP-kinases in the spinal cord and a subsequent decrease in pain-relevant induction of c-fos, which constitutes a reliable marker of elevated activity in spinal cord neurons following peripheral noxious stimulation. In summary, our results indicate that activation of AMPKα2 might represent a novel therapeutic option for the treatment of inflammation-associated pain, providing analgesia with fewer unwanted side effects. AMPK activation is associated with beneficial effects on diabetes and obesity. In addition, we have shown analgesic properties of pharmacologic AMPK activation in inflammatory nociception, indicating that AMPK might serve as a novel therapeutic target in pain with fewer unwanted side effects. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase.

    PubMed

    Park, Chan Sun; Bang, Bo-Ram; Kwon, Hyouk-Soo; Moon, Keun-Ai; Kim, Tae-Bum; Lee, Ki-Young; Moon, Hee-Bom; Cho, You Sook

    2012-12-15

    Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease. To investigate the underlying mechanism of metformin, oxidative stress levels and AMP-activated protein kinase (AMPK) activation were assessed. To further elucidate the role of AMPK, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) as a specific activator of AMPK and employed AMPKα1-deficient mice as an asthma model. The role of metformin and AMPK in tissue fibrosis was evaluated using a bleomycin-induced acute lung injury model and in vitro experiments with cultured fibroblasts. Metformin suppressed eosinophilic inflammation and significantly reduced peribronchial fibrosis, smooth muscle layer thickness, and mucin secretion. Enhanced AMPK activation and decreased oxidative stress in lungs was found in metformin-treated asthmatic mice. Similar results were observed in the AICAR-treated group. In addition, the enhanced airway inflammation and fibrosis in heterozygous AMPKα1-deficient mice were induced by both allergen and bleomycin challenges. Fibronectin and collagen expression was diminished by metformin through AMPKα1 activation in cultured fibroblasts. Therefore metformin reduced both airway inflammation and remodeling at least partially through the induction of AMPK activation and decreased oxidative stress. These data provide insight into the beneficial role of metformin as a novel therapeutic drug for chronic asthma.

  2. Global physical activity levels: surveillance progress, pitfalls, and prospects.

    PubMed

    Hallal, Pedro C; Andersen, Lars Bo; Bull, Fiona C; Guthold, Regina; Haskell, William; Ekelund, Ulf

    2012-07-21

    To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes to increase activity levels and to reduce the burden of non-communicable diseases.

  3. Active learning reduces annotation time for clinical concept extraction.

    PubMed

    Kholghi, Mahnoosh; Sitbon, Laurianne; Zuccon, Guido; Nguyen, Anthony

    2017-10-01

    To investigate: (1) the annotation time savings by various active learning query strategies compared to supervised learning and a random sampling baseline, and (2) the benefits of active learning-assisted pre-annotations in accelerating the manual annotation process compared to de novo annotation. There are 73 and 120 discharge summary reports provided by Beth Israel institute in the train and test sets of the concept extraction task in the i2b2/VA 2010 challenge, respectively. The 73 reports were used in user study experiments for manual annotation. First, all sequences within the 73 reports were manually annotated from scratch. Next, active learning models were built to generate pre-annotations for the sequences selected by a query strategy. The annotation/reviewing time per sequence was recorded. The 120 test reports were used to measure the effectiveness of the active learning models. When annotating from scratch, active learning reduced the annotation time up to 35% and 28% compared to a fully supervised approach and a random sampling baseline, respectively. Reviewing active learning-assisted pre-annotations resulted in 20% further reduction of the annotation time when compared to de novo annotation. The number of concepts that require manual annotation is a good indicator of the annotation time for various active learning approaches as demonstrated by high correlation between time rate and concept annotation rate. Active learning has a key role in reducing the time required to manually annotate domain concepts from clinical free text, either when annotating from scratch or reviewing active learning-assisted pre-annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Latrepirdine (Dimebon™) enhances autophagy and reduces intracellular GFP-Aβ42 levels in yeast

    PubMed Central

    Bharadwaj, Prashant R.; Verdile, Giuseppe; Barr, Renae K.; Gupta, Veer; Steele, John W.; Lachenmayer, M. Lenard; Yue, Zhenyu; Ehrlich, Michelle E.; Petsko, Gregory; Ju, Shulin; Ringe, Dagmar; Sankovich, Sonia E.; Caine, Joanne M.; Macreadie, Ian G.; Gandy, Sam; Martins, Ralph N.

    2012-01-01

    Latrepirdine (Dimebon™), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation of aggregated or misfolded protein such as Alzheimer’s disease (AD) and has been shown to promote the removal of α-synuclein protein aggregates in vivo. An important pathway for removal of aggregated or misfolded proteins is the autophagy-lysosomal pathway, which has been implicated in AD pathogenesis, and enhancing this pathway has been shown to have therapeutic potential in AD and other proteinopathies. Here we use a yeast model Saccharomyces cerevisiae, to investigate whether latrepirdine can enhance autophagy and reduce levels of Aβ42 aggregates. Latrepirdine was shown to up-regulate yeast vacuolar (lysosomal) activity and promote transport of the autophagic marker (Atg8) to the vacuole. Using an in vitro GFP tagged Aβ yeast expression system, we investigated whether latrepirdine-enhanced autophagy was associated with a reduction in levels of intracellular GFP-Aβ42. GFP-Aβ42 was localized into punctate patterns compared to the diffuse cytosolic pattern of GFP and the GFP-Aβ42 (19:34), which does not aggregate. In the autophagy deficient mutant (Atg8Δ), GFP-Aβ42 showed a more diffuse cytosolic localization, reflecting the inability of this mutant to sequester GFP-Aβ42. Similar to rapamycin, we observed that latrepirdine significantly reduced GFP-Aβ42 in wild-type compared to the Atg8Δ mutant. Further, latrepirdine treatment attenuated Aβ42-induced toxicity in wild-type cells but not in the Atg8Δ mutant. Together, our findings provide evidence for a novel mechanism of action for latrepirdine in inducing autophagy and reducing intracellular levels of GFP-Aβ42. PMID:22903131

  5. Increased iron level in phytase-supplemented diets reduce performance and nutrient utilisation in broiler chickens.

    PubMed

    Akter, M; Iji, P A; Graham, H

    2017-04-11

    1. The effect of different levels of dietary iron on phytase activity and its subsequent effect on broiler performance was investigated in a 3 x 2 factorial arrangement. A total of 360 day-old Ross 308 male broiler chicks were distributed to 6 experimental diets, formulated with three levels of Fe (60, 80 and 100 mg/kg) and two levels of phytase (0, 500 FTU/kg). 2. Phytase supplemented to mid-Fe diets increased feed consumption more than the non-supplemented diet at d 24. From hatch to d 35, Fe x phytase interaction significantly influenced the FI, BWG and FCR. The high-Fe diet supplemented with phytase significantly reduced FI and BWG of broilers than those supplemented with low or mid-Fe diets. The overall FCR was significantly better in birds fed on the mid-Fe diets with phytase supplementation. 3. A significant improvement in ileal digestibility of N, P, Mg and Fe was observed in birds feed diets containing 60 mg Fe/kg, with significant interaction between Fe and phytase. 4. Phytase improved the bone breaking strength when supplemented to low or mid-Fe diets, compared to the non-supplemented diets. There was a significant Fe x phytase interaction effect. Tibia Fe content was higher in birds fed on phytase-free diets with high Fe but the reverse was the case when phytase was added and their interaction was significant. High dietary Fe significantly increased the accumulation of Fe in liver. 5. Phytase improved Ca-Mg-ATPase, Ca-ATPase and Mg-ATPase activities in jejunum when supplemented to the diet containing 80 mg Fe/kg. 6. This study indicates that high (100 mg/kg) dietary Fe inhibited phytase efficacy and subsequently reduced the overall performance and nutrient utilisation of broilers.

  6. Biological activity of oxidized and reduced iodinated bombesins

    SciTech Connect

    Vigna, S.R.; Giraud, A.S.; Reeve, J.R. Jr.; Walsh, J.H.

    1988-07-01

    A method is reported for preparing oxidized and reduced iodinated Tyr4-bombesin. Iodogen was used to iodinate Tyr4-bombesin and the reaction products were separated by reverse-phase HPLC. The peak of oxidized label was then reduced by incubation with 725 mM dithiothreitol at 80 degrees C (pH 8.0) for one hour and the reaction products separated by HPLC as before. The reduced but not oxidized peaks of /sup 125/I-Tyr4-bombesin stimulated amylase release from rat pancreatic acini in vitro. We conclude that oxidation of bombesin producing C-terminal methionine sulfoxide destroys the biological activity of the peptide and that this form of oxidation can be reversed.

  7. Novel active noise-reducing headset using earshell vibration control.

    PubMed

    Rafaely, Boaz; Carrilho, Joao; Gardonio, Paolo

    2002-10-01

    Active noise-reducing (ANR) headsets are available commercially in applications varying from aviation communication to consumer audio. Current ANR systems use passive attenuation at high frequencies and loudspeaker-based active noise control at low frequencies to achieve broadband noise reduction. This paper presents a novel ANR headset in which the external noise transmitted to the user's ear via earshell vibration is reduced by controlling the vibration of the earshell using force actuators acting against an inertial mass or the earshell headband. Model-based theoretical analysis using velocity feedback control showed that current piezoelectric actuators provide sufficient force but require lower stiffness for improved low-frequency performance. Control simulations based on experimental data from a laboratory headset showed that good performance can potentially be achieved in practice by a robust feedback controller, while a single-frequency real-time control experiment verified that noise reduction can be achieved using earshell vibration control.

  8. Mutagenic activation reduces carcinogenic activity of ortho-aminoazotoluene for mouse liver.

    PubMed

    Ovchinnikova, L P; Bogdanova, L A; Kaledin, V I

    2013-03-01

    Pentachlorophenol (aromatic amine and azo stain metabolic stimulation inhibitor) reduced the hepatocarcinogenic activity of 4-aminoazobenzene and reduced that of ortho-aminoazotoluene in suckling mice. Both 4-aminoazobenzene and ortho-aminoazotoluene exhibited mutagenic activity in Ames' test in vitro on S. typhimurium TA 98 strain with activation with liver enzymes; this mutagenic activity was similarly suppressed by adding pentachlorophenol into activation medium. Induction of xenobiotic metabolism enzymes, stimulating the mutagenic activity of ortho-aminoazotoluene, suppressed its carcinogenic effect on mouse liver. Hence, ortho-aminotoluene (the initial compound), but not its mutagenic metabolites, was the direct active hepatocarcinogen for mice.

  9. 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.

  10. Reducing Igf-1r Levels Leads To Paradoxical and Sexually Dimorphic Effects in HD Mice

    PubMed Central

    Corrochano, Silvia; Renna, Maurizio; Osborne, Georgina; Carter, Sarah; Stewart, Michelle; May, Joel; Bates, Gillian P.; Brown, Steve D. M.; Rubinsztein, David C.; Acevedo-Arozena, Abraham

    2014-01-01

    Many of the neurodegenerative diseases that afflict people in later life are associated with the formation of protein aggregates. These so-called “proteinopathies” include Alzheimer’s disease (AD) and Huntington’s disease (HD). The insulin/insulin-like growth factor signalling (IIS) pathway has been proposed to modulate such diseases in model organisms, as well as the general ageing process. In this pathway, insulin-like growth factor binds to insulin-like growth factor receptors, such as the insulin-like growth factor 1 receptor (IGF-1R). Heterozygous deletion of Igf-1r has been shown to lead to increased lifespan in mice. Reducing the activity of this pathway had benefits in a HD C. elegans model, and some of these may be attributed to the expected inhibition of mTOR activity resulting in an increase in autophagy, which would enhance mutant huntingtin clearance. Thus, we tested if heterozygous deletion of Igf-1r would lead to benefits in HD related phenotypes in the mouse. Surprisingly, reducing Igf-1r levels led to some beneficial effects in HD females, but also led to some detrimental effects in HD males. Interestingly, Igf-1r deficiency had no discernible effects on downstream mTOR signalling in HD mice. These results do not support a broad beneficial effect of diminishing the IIS pathway in HD pathology in a mammalian system. PMID:25140802

  11. 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.

  12. Loneliness Predicts Reduced Physical Activity: Cross-Sectional & Longitudinal Analyses

    PubMed Central

    Hawkley, Louise C.; Thisted, Ronald A.; Cacioppo, John T.

    2009-01-01

    Objective To determine cross-sectional and prospective associations between loneliness and physical activity, and to evaluate the roles of social control and emotion regulation as mediators of these associations. Design A population-based sample of 229 White, Black, and Hispanic men and women, age 50 to 68 years at study onset, were tested annually for each of 3 years. Main Outcome Measures Physical activity probability, and changes in physical activity probability over a 3-year period. Results Replicating and extending prior cross-sectional research, loneliness was associated with a significantly reduced odds of physical activity (OR = 0.65 per SD of loneliness) net of sociodemographic variables (age, gender, ethnicity, education, income), psychosocial variables (depressive symptoms, perceived stress, hostility, social support), and self-rated health. This association was mediated by hedonic emotion regulation, but not by social control as indexed by measures of social network size, marital status, contact with close ties, group membership, or religious group affiliation. Longitudinal analyses revealed that loneliness predicted diminished odds of physical activity in the next two years (OR = 0.61), and greater likelihood of transitioning from physical activity to inactivity (OR = 1.58). Conclusion Loneliness among middle and older age adults is an independent risk factor for physical inactivity and increases the likelihood that physical activity will be discontinued over time. PMID:19450042

  13. Sequential activation of multiple grounding pads reduces skin heating.

    PubMed

    Schutt, D J; Haemmerich, D

    2006-01-01

    Radio frequency (RF) tumor ablation has become an accepted treatment modality for tumors not amenable to surgery. The need for larger ablation zones has required increase in RF generator power, with current generation devices delivering 200-250 W. Skin burns due to ground pad heating have become a common complication and are now a limiting factor for further increase in ablation zone and generator power. We performed ex vivo experiments with three ground pads (5 x 5 cm) placed on a tissue phantom. We applied 100 W of power for 12 min between the pads, and an RF electrode while we measured leading edge temperature below each pad, and temperature profile on the pads using temperature-sensitive LCD-paper. We compared conventional operation (i.e. simultaneous connection of all three pads) to sequential activation of the pads where each pad is only active for approximately 0.5 s. The timing during sequential activation was adjusted to keep leading edge temperature equal between the pads. Temperature rise below the leading edge for proximal, middle and distal ground pad was 10.7 +/- 1.04, 1.0 +/- 0.15 and 0.3 +/- 0.07 degrees C for conventional operation, and 4.8 +/- 0.16, 4.4 +/- 0.20 and 4.5 +/- 0.35 degrees C for sequentially activated operation. The maximum leading edge temperature rise was more than twice as high for conventional compared to switched operation (p<0.001). Sequential activation of multiple ground pads resulted in reduced maximum leading edge temperature, and allows control of each pad such that leading edge temperature of all pads is the same. This may reduce the incidence of ground pad burns by allowing each pad to reach same temperatures independent of location, and may allow higher power RF generators due to reduced skin heating.

  14. Thrombotic risk of reduced ADAMTS13 activity in patients with antiphospholipid antibodies.

    PubMed

    Lee, Seung Jun; Kim, Ji-Eun; Han, Kyou-Sup; Kim, Hyun Kyung

    2016-12-01

    Antiphospholipid syndrome (APS) is an autoimmune disease in which antiphospholipid antibodies (aPLs) are generated. Previous studies show concurrence of APS and thrombotic thrombocytopenic purpura; therefore it is plausible to assume that anti-ADAMTS13 autoantibody is also involved in the pathophysiology of APS. We investigated the clinical significance of ADAMTS13 activity and anti-ADAMTS13 antibody in patients with aPLs. Two hundred and sixteen patients with positive lupus anticoagulant and/or anticardiolipin antibody were included. ADAMTS13 activity and anti-ADAMTS13 antibody were measured using fluorescence resonance energy-transfer technology and ELISA, respectively. Reduced ADAMTS13 activity was observed in 40.3% (87/216) of patients with aPLs. Although 33.8% (73/216) of patients were positive for anti-ADAMTS13 antibody, 41 of these 73 patients had normal levels of ADAMTS13 activity. Reduced ADAMTS13 activity was a significant risk factor for thrombotic events. Thrombotic events and age contributed to the reduced level of ADAMTS13 activity. Presence of anti-ADAMTS13 antibody did not show any association with the level of ADAMTS13 activity. Patients with autoimmune diseases tended to show higher levels of anti-ADAMTS13 antibody. Our findings suggest that reduced ADAMTS13 activity is a significant thrombotic risk factor in patients with aPLs irrespective of the presence of anti-ADAMTS13 antibody. Presence of anti-ADAMTS13 antibody is not seen with reduced activity and it tends to be increased in patients with autoimmune diseases.

  15. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels

    PubMed Central

    Jiang, Xian-cheng; Bruce, Can; Mar, Jefferson; Lin, Min; Ji, Yong; Francone, Omar L.; Tall, Alan R.

    1999-01-01

    It has been proposed that the plasma phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids and cholesterol from triglyceride-rich lipoproteins (TRL) into high-density lipoproteins (HDL). To evaluate the in vivo role of PLTP in lipoprotein metabolism, we used homologous recombination in embryonic stem cells and produced mice with no PLTP gene expression. Analysis of plasma of F2 homozygous PLTP–/– mice showed complete loss of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and partial loss of free cholesterol transfer activities. Moreover, the in vivo transfer of [3H]phosphatidylcholine ether from very-low-density proteins (VLDL) to HDL was abolished in PLTP–/– mice. On a chow diet, PLTP–/– mice showed marked decreases in HDL phospholipid (60%), cholesterol (65%), and apo AI (85%), but no significant change in non-HDL lipid or apo B levels, compared with wild-type littermates. On a high-fat diet, HDL levels were similarly decreased, but there was also an increase in VLDL and LDL phospholipids (210%), free cholesterol (60%), and cholesteryl ester (40%) without change in apo B levels, suggesting accumulation of surface components of TRL. Vesicular lipoproteins were shown by negative-stain electron microscopy of the free cholesterol– and phospholipid-enriched IDL/LDL fraction. Thus, PLTP is the major factor facilitating transfer of VLDL phospholipid into HDL. Reduced plasma PLTP activity causes markedly decreased HDL lipid and apoprotein, demonstrating the importance of transfer of surface components of TRL in the maintenance of HDL levels. Vesicular lipoproteins accumulating in PLTP–/– mice on a high-fat diet could influence the development of atherosclerosis. PMID:10079112

  16. 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

  17. Tumor hypoxia causes DNA hypermethylation by reducing TET activity

    PubMed Central

    Kuchnio, Anna; Ploumakis, Athanasios; Ghesquière, Bart; Van Dyck, Laurien; Boeckx, Bram; Schoonjans, Luc; Hermans, Els; Amant, Frederic; Kristensen, Vessela N.; Peng Koh, Kian; Mazzone, Massimiliano; Coleman, Mathew; Carell, Thomas; Carmeliet, Peter; Lambrechts, Diether

    2016-01-01

    Summary Hypermethylation of tumor suppressor gene (TSG) promoters confers growth advantages to cancer cells, but how these changes arise is poorly understood. Here, we report that tumor hypoxia reduces the activity of oxygen-dependent TET enzymes, which catalyze DNA de-methylation through 5-methylcytosine oxidation. This occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, HIF activity or reactive oxygen, but directly depends on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. Also in patients, TSG promoters are markedly more methylated in hypoxic tumors, independently of proliferation, stromal cell infiltration and tumor characteristics. Our data suggest cellular selection of hypermethylation events, with almost half of them being ascribable to hypoxia across tumor types. Accordingly, increased hypoxia after vessel pruning in murine breast tumors increases hypermethylation, while restored tumor oxygenation by vessel normalization abrogates this effect. Tumor hypoxia thus acts as a novel regulator underlying DNA methylation. PMID:27533040

  18. 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

  19. Novel weight-reducing activity of Galega officinalis in mice.

    PubMed

    Palit, P; Furman, B L; Gray, A I

    1999-11-01

    Galega officinalis (galega, Goat's Rue, French Lilac) is well known for its hypoglycaemic action and has been used as part of a plant mixture in the treatment of diabetes mellitus. During pharmacological investigations of an ethanolic extract of a powdered mixture of equal proportions of G. officinalis, Cressa cretica, Mangifera indica and Syzygium jambolanum, a weight reducing effect of galega was discovered. In this study we have investigated the novel weight reducing effect of galega in mice. Galega herb (10% w/w in the diet) caused a significant reduction in body weight in both normal and genetically obese (ob/ob) animals treated for 28 days when compared with respective controls (P < 0.01). In normal mice, the weight loss was reversible and initially associated with a transient reduction in food intake but was then maintained even in the presence of increased eating above the control level. Pair-fed normal mice receiving galega for seven days also showed significant weight loss (P < 0.01, compared with the control) in the presence of increasing food intake. In sharp contrast, weight loss in galega-treated ob/ob mice was accompanied by a persistent reduction in food intake over the 28-day treatment period. Post-mortem examinations of all galega-treated mice revealed a striking absence of body fat. Serum glucose was significantly reduced in both strains of mice receiving galega for 28 days (P < 0.01), whereas serum insulin was significantly reduced only in obese mice (P < 0.01). In summary, together with its established hypoglycaemic effects, galega has a novel weight reducing action that, in normal mice, is largely independent of a reduction in food intake. The mechanism of the weight reducing action of galega is unclear but involves loss of body fat.

  20. Reduced activation in isometric muscle action after lengthening contractions is not accompanied by reduced performance fatigability

    PubMed Central

    Seiberl, W.; Hahn, D.; Paternoster, F. K.

    2016-01-01

    After active lengthening contractions, a given amount of force can be maintained with less muscle activation compared to pure isometric contractions at the same muscle length and intensity. This increase in neuromuscular efficiency is associated with mechanisms of stretch-induced residual force enhancement. We hypothesized that stretch-related increase in neuromuscular efficiency reduces fatigability of a muscle during submaximal contractions. 13 subjects performed 60 s isometric knee extensions at 60% of maximum voluntary contraction (MVC) with and without prior stretch (60°/s, 20°). Each 60 s trial was preceded and followed by neuromuscular tests consisting of MVCs, voluntary activation (VA) and resting twitches (RT), and there was 4 h rest between sets. We found a significant (p = 0.036) 10% reduction of quadriceps net-EMG after lengthening compared to pure isometric trials. However, increase in neuromuscular efficiency did not influence the development of fatigue. Albeit we found severe reduction of MVC (30%), RT (30%) and VA (5%) after fatiguing trials, there were no differences between conditions with and without lengthening. As the number of subjects showing no activation reduction increased with increasing contraction time, intensity may have been too strenuous in both types of contractions, such that a distinction between different states of fatigue was not possible anymore. PMID:27966620

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

    PubMed

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

    2013-09-03

    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 nonlinear relationships between BDE-209 exposures and thyroid dysfunction.

  2. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

    PubMed Central

    Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

    2011-01-01

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782

  3. Consequences for Ground Level Enhancements (GLEs) from a Reduced Heliomagnetic Field

    NASA Astrophysics Data System (ADS)

    Kahler, S.

    2007-12-01

    A recent assessment of the long-term records of solar energetic particle (SEP) events by McCracken (Space Weather, 2007) has concluded that the frequency of occurrence of large SEP events is smallest for the most active solar cycles. In particular, the E > 4 GeV fluences were ~ 10 times larger and 4 times more frequent in the 20 years preceding the onset of the space era in 1958. A return in the near future to the solar activity level characteristic of the Gleissberg minima of 1800-1820 and 1875-1910 could introduce an era of much more energetic SEP events with longer fluences than those observed since 1958. The working explanation of this variation of SEP event intensity is that the lower solar activity produces weaker magnetic fields, which decrease the coronal Alfven speeds, which reduce the compression ratios of shocks driven by coronal mass ejections (CMEs). This explanation implicitly assumes not only that other variables such as solar wind density and CME speeds are unchanged through a declining heliospheric magnetic field, but also assumes the existence of the controversial long-term increase in the heliospheric field. We examine these assumptions from two points of view: 1) the relationship of solar magnetic fields to CME and solar wind characteristics, and 2) our best knowledge of the long-term variations in solar wind properties.

  4. Human ribosomes from cells with reduced dyskerin levels are intrinsically altered in translation.

    PubMed

    Penzo, Marianna; Rocchi, Laura; Brugiere, Sabine; Carnicelli, Domenica; Onofrillo, Carmine; Couté, Yohann; Brigotti, Maurizio; Montanaro, Lorenzo

    2015-08-01

    Dyskerin is a pseudouridine (ψ) synthase involved in fundamental cellular processes including uridine modification in rRNA and small nuclear RNA and telomere stabilization. Dyskerin functions are altered in X-linked dyskeratosis congenita (X-DC) and cancer. Dyskerin's role in rRNA pseudouridylation has been suggested to underlie the alterations in mRNA translation described in cells lacking dyskerin function, although relevant direct evidences are currently lacking. Our purpose was to establish definitely whether defective dyskerin function might determine an intrinsic ribosomal defect leading to an altered synthetic activity. Therefore, ribosomes from dyskerin-depleted human cells were purified and 1) added to a controlled reticulocyte cell-free system devoid of ribosomes to study mRNA translation; 2) analyzed for protein contamination and composition by mass spectrometry, 3) analyzed for global pseudouridylation levels. Ribosomes purified from dyskerin-depleted cells showed altered translational fidelity and internal ribosome entry site (IRES)-mediated translation. These ribosomes displayed reduced uridine modification, whereas they were not different in terms of protein contamination or ribosomal protein composition with respect to ribosomes from matched control cells with full dyskerin activity. In conclusion, lack of dyskerin function in human cells induces a defect in rRNA uridine modification, which is sufficient to alter ribosome activity.

  5. 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…

  6. 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…

  7. 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

  8. Reduced brain activation in violent adolescents during response inhibition.

    PubMed

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

    2016-02-18

    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.

  9. Raising low 'patient activation' rates among Hispanic immigrants may equal expanded coverage in reducing access disparities.

    PubMed

    Cunningham, Peter J; Hibbard, Judith; Gibbons, Claire B

    2011-10-01

    There is a growing consensus that activating consumers to become better managers of their health is an essential component of US health care reform. We measured how activated blacks, whites, and Hispanics are-that is, how confident, skillful, and knowledgeable they are about taking an active role in improving their health and health care. We found that patient activation among blacks and Hispanics was low, relative to that of whites. For example, 24.8 percent of Hispanics were at the highest level of patient activation, compared to 39.5 percent of blacks and 45.3 percent of whites. Among Hispanic immigrants, low acculturation and lack of familiarity with the US health care system contribute to low activation. The findings indicate that increasing activation levels among Hispanic immigrants may be as important as expanding insurance coverage in reducing disparities in unmet medical need.

  10. Free 25-hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxyvitamin D levels.

    PubMed

    Bikle, D D; Halloran, B P; Gee, E; Ryzen, E; Haddad, J G

    1986-09-01

    We determined the free fraction of 25-dihydroxyvitamin D (25OHD) in the serum of subjects with clinical evidence of liver disease and correlated these measurements to the levels of vitamin D binding protein and albumin. These subjects when compared to normal individuals had lower total 25OHD levels, higher percent free 25OHD levels, but equivalent free 25OHD levels. These subjects also had reduced vitamin D binding protein and albumin concentrations. The total concentration of 25OHD correlated positively with both vitamin D binding protein and albumin, whereas the percent free 25OHD correlated negatively with vitamin D binding protein and albumin. The free 25OHD levels did not correlate with either vitamin D binding protein or albumin. We conclude that total vitamin D metabolite measurements may be misleading in the evaluation of the vitamin D status of patients with liver disease, and recommend that free 25OHD levels also be determined before making a diagnosis of vitamin D deficiency.

  11. 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.

  12. Reduced superoxide dismutase activity in xeroderma pigmentosum fibroblasts

    SciTech Connect

    Nishigori, C.; Miyachi, Y.; Imamura, S.; Takebe, H. )

    1989-10-01

    This study was performed in order to assess the possible protective effect of superoxide dismutase (SOD) on ultraviolet (UV) damage in xeroderma pigmentosum (XP) fibroblasts. SOD activity in fibroblasts originating from seven xeroderma pigmentosum (XP) patients was significantly lower than that in normal cells (p less than 0.005). Average SOD activity in XP cells belonging to complementation group A was 3.68 +/- 0.54 (n = 7) and that in normal human cells was 5.79 +/- 1.59 (n = 6). Addition of SOD before and during UV irradiation (UVB and UVC) to the cells caused no change in the amount of unscheduled DNA synthesis and UV survival. A possible involvement of reduced SOD in XP and a possible protective effect by SOD on UV damage is discussed.

  13. Indoor Physical Activity Reduces All-Cause and Cardiovascular Disease Mortality Among Elderly Women

    PubMed Central

    Park, Soyoung; Lee, Joongyub; Kang, Dong Yoon; Rhee, Chul Woo

    2012-01-01

    Objectives The aim of this study was to investigate whether a medium to high degree of total physical activity and indoor physical activity were associated with reduced all-cause and cardiovascular mortality among elderly Korean women. Methods A prospective cohort study was done to evaluate the association between physical activity and mortality. The cohort was made up of elderly (≥65 years of age) subjects. Baseline information was collected with a self-administered questionnaire and linked to death certificates retrieved from a database. Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence interval (CI) levels. Results Women who did not suffer from stroke, cancer, or ischemic heart disease were followed for a median of 8 years (n=5079). A total of 1798 all-cause deaths were recorded, of which 607 (33.8%) were due to cardiovascular disease. The group with the highest level of total physical activity and indoor physical activity was significantly associated to a reduced all-cause mortality (HR, 0.60; 95% CI, 0.51 to 0.71 and HR, 0.58; 95% CI, 0.50 to 0.67, respectively) compared to the group with the lowest level of total physical activity and indoor physical activity. Additionally, the group with the highest level of total physical activity and indoor physical activity was significantly associated to a lower cardiovascular disease mortality (HR, 0.53; 95% CI, 0.40 to 0.71 and HR, 0.51; 95% CI, 0.39 to 0.67, respectively) compared to the group with the lowest level of total physical activity and indoor physical activity. Conclusions Our study showed that regular indoor physical activity among elderly Korean women has healthy benefits. PMID:22389755

  14. 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.

  15. 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.

  16. 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.

  17. Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease.

    PubMed

    Lim, M A; Selak, M A; Xiang, Z; Krainc, D; Neve, R L; Kraemer, B C; Watts, J L; Kalb, R G

    2012-01-18

    A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease.

  18. Tumour hypoxia causes DNA hypermethylation by reducing TET activity.

    PubMed

    Thienpont, Bernard; Steinbacher, Jessica; Zhao, Hui; D'Anna, Flora; Kuchnio, Anna; Ploumakis, Athanasios; Ghesquière, Bart; Van Dyck, Laurien; Boeckx, Bram; Schoonjans, Luc; Hermans, Els; Amant, Frederic; Kristensen, Vessela N; Peng Koh, Kian; Mazzone, Massimiliano; Coleman, Mathew; Carell, Thomas; Carmeliet, Peter; Lambrechts, Diether

    2016-09-01

    Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, hypoxia-inducible factor activity or reactive oxygen species, and depends directly on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. In patients, tumour suppressor gene promoters are markedly more methylated in hypoxic tumour tissue, independent of proliferation, stromal cell infiltration and tumour characteristics. Our data suggest that up to half of hypermethylation events are due to hypoxia, with these events conferring a selective advantage. Accordingly, increased hypoxia in mouse breast tumours increases hypermethylation, while restoration of tumour oxygenation abrogates this effect. Tumour hypoxia therefore acts as a novel regulator of DNA methylation.

  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. 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.

  1. 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

  2. Phenotypic Diversity and Altered Environmental Plasticity in Arabidopsis thaliana with Reduced Hsp90 Levels

    PubMed Central

    Sangster, Todd A.; Bahrami, Adam; Wilczek, Amity; Watanabe, Etsuko; Schellenberg, Kurt; McLellan, Catherine; Kelley, Alicia; Kong, Sek Won; Queitsch, Christine; Lindquist, Susan

    2007-01-01

    The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to preventing the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by the necessity of reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, increases morphological diversity, and decreases the developmental stability of repeated characters. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a

  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. COPE Method Implementation Program to Reduce Communication Apprehension Level in Full Day Yunior High School Students

    NASA Astrophysics Data System (ADS)

    Prasetyo, A. R.

    2017-02-01

    This study was aimed to explore the effect of COPE method to reduce communication apprehension level of students in Early Adolescence who become Full Day Junior High School students. Full Day Junior High School students, especially in Surabaya coastal area, have more demands to develop the communication aspects such as group discussions and presentations and extracurricular activities. Higher demands to develop such aspects of communication may cause them to experience communication apprehension. The subject was Full Day School students totaling 31 students. The design of the research was experimental design. The experimental method used was a non-randomized pretest posttest control group design and purposive sampling was also used. COPE method is a process that consists of four main stages where people are trying to deal with and control of stressful situations as a result of the problem being faced by conducting cognitive and behavioral changes. Four main stages COPE method is Calming the nervous system, Originating an imaginative plan, Persisting in the face of obstacles and failure, and Evaluating and adjusting the plan. Results of quantitative analysis based on U-Mann Whitney Test shows significant effect on the COPE Method to decrease anxiety levels of communication (0.000 <0.005).

  5. Human Development Program: Level V Activity Guide.

    ERIC Educational Resources Information Center

    Ball, Geraldine

    The curriculum guide presents the activities component of the Human Development Program for grade 5. The Human Development Program (HDP) is an affective curricular approach developed by psychologists to help teachers instill responsibility and self-confidence in children. The activity guide presents topics and directions for 180 sequential Human…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  7. Reduced administered activity, reduced acquisition time, and preserved image quality for the new CZT camera.

    PubMed

    Oddstig, Jenny; Hedeer, Fredrik; Jögi, Jonas; Carlsson, Marcus; Hindorf, Cecilia; Engblom, Henrik

    2013-02-01

    For a 1-day myocardial perfusion SPECT (MPS) the recommendations for administered activity stated in the EANM guidelines results in an effective dose of up to 16 mSv per patient. Recently, a gamma camera system, based on cadmium zinc telluride (CZT) technology, was introduced. This technique has the potential to reduce the effective dose and scan time compared to the conventional NaI gamma camera. The aim of this study was to investigate if the effective dose can be reduced with a preserved image quality using CZT technology in MPS. In total, 150 patients were included in the study. All underwent a 1-day (99m)Tc-tetrofosmin stress-rest protocol and were divided into three subgroups (n = 50 in each group) with 4, 3, and 2.5 MBq/kg body weight of administered activity in the stress examination, respectively. The acquisition time was increased in proportion to the decrease in administered activity. All examinations were analyzed for image quality by visual grading on a 4-point scale (1 = poor, 2 = adequate, 3 = good, 4 = excellent), by two expert readers. The total effective dose (stress + rest) decreased from 9.3 to 5.8 mSv comparing 4 to 2.5 MBq/kg body weight. For the patients undergoing stress examination only (35%) the effective dose, administrating 2.5 MBq/kg, was 1.4 mSv. The image acquisition times for 2.5 MBq/kg body weight were 475 and 300 seconds (stress and rest) compared to 900 seconds for each when using conventional MPS. The average image quality was 3.7 ± 0.5, 3.8 ± 0.5, and 3.8 ± 0.4 for the stress images and 3.5 ± 0.6, 3.6 ± 0.6, and 3.5 ± 0.6 for the rest images and showed no statistically significant difference (P = .62) among the 4, 3, and 2.5 MBq/kg groups. The new CZT technology can be used to considerably decrease the effective dose and acquisition time for MPS with preserved high image quality.

  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. Postmenopausal therapy reduces catalase activity and attenuates cardiovascular risk.

    PubMed

    Castanho, Vera S; Nakamura, Rui Tsutomu; Pinto-Neto, Aarão M; Faria, Eliana Cotta de

    2012-11-01

    Menopause can lead to alterations in women's health, with changes in the oxidative status of postmenopausal women in whom information regarding the influence of hormone therapy (HT) on antioxidant enzyme activities is limited. To evaluate the influence of HT on catalase activity; concentrations of lipids and lipoprotein, cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, nitrates, high-sensitivity C-reactive protein and carotid thickness in postmenopausal women. Ninety-four consecutive women were allocated to one of four groups, without HT and with HT. The latter group was subdivided into women using estrogen and those using estrogen plus progestogen therapy. Plasma biochemical parameters and common carotid intima-media thickness measurements were performed. HT antagonized the decrease in catalase activity after menopause, but had no effect on the levels of cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, lipid peroxide, nitrate, high-sensitivity C-reactive protein, or on the common carotid intima-media thickness. Multivariate analysis showed that estrogen-based HT attenuated the relationship between cardiovascular risk factors and the intima-media thickness of the common carotid. This study indicates that HT in postmenopausal women produces beneficial antioxidant and anti-atherosclerotic effects by ameliorating the plasma lipid and lipoprotein profiles, increasing plasma catalase activity and attenuating the association between cardiovascular risk factors and early atherosclerosis.

  10. ActivityAware: An App for Real-Time Daily Activity Level Monitoring on the Amulet Wrist-Worn Device.

    PubMed

    Boateng, George; Batsis, John A; Halter, Ryan; Kotz, David

    2017-03-01

    Physical activity helps reduce the risk of cardiovascular disease, hypertension and obesity. The ability to monitor a person's daily activity level can inform self-management of physical activity and related interventions. For older adults with obesity, the importance of regular, physical activity is critical to reduce the risk of long-term disability. In this work, we present ActivityAware, an application on the Amulet wrist-worn device that measures daily activity levels (sedentary, moderate and vigorous) of individuals, continuously and in real-time. The app implements an activity-level detection model, continuously collects acceleration data on the Amulet, classifies the current activity level, updates the day's accumulated time spent at that activity level, logs the data for later analysis, and displays the results on the screen. We developed an activity-level detection model using a Support Vector Machine (SVM). We trained our classifiers using data from a user study, where subjects performed the following physical activities: sit, stand, lay down, walk and run. With 10-fold cross validation and leave-one-subject-out (LOSO) cross validation, we obtained preliminary results that suggest accuracies up to 98%, for n=14 subjects. Testing the ActivityAware app revealed a projected battery life of up to 4 weeks before needing to recharge. The results are promising, indicating that the app may be used for activity-level monitoring, and eventually for the development of interventions that could improve the health of individuals.

  11. 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.

  12. Bird activity levels related to weather

    USGS Publications Warehouse

    Robbins, C.S.; Ralph, C. John; Scott, J. Michael

    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

  13. Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism.

    PubMed

    Tang, M W; van Nierop, F S; Koopman, F A; Eggink, H M; Gerlag, D M; Chan, M W; Zitnik, R; Vaz, F M; Romijn, J A; Tak, P P; Soeters, M R

    2017-04-08

    A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.

  14. Tumour reducing and anticarcinogenic activity of selected spices.

    PubMed

    Unnikrishnan, M C; Kuttan, R

    1990-05-15

    Tumour reducing activity of extracts of eight commonly used spices in India were studied in mice transplanted intraperitoneally with Ehrlich ascites tumour. Oral administration of extracts of black pepper, asafoetida, pippali and garlic could increase the percentage of life span in these mice by 64.7%, 52.9%, 47% and 41.1%, respectively. However intraperitoneal administration of spice extracts did not produce any significant reduction in tumour growth except for sesame (38.8%). Garlic extract and asafoetida extracts also inhibited two stage chemical carcinogenesis induced by 7,12 dimethyl benzanthracene and croton oil on mice skin with significant reduction in papiloma formation. These results indicate the potential use of spices as anti-cancer agents as well as anti-tumour promoters.

  15. 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

  16. Monthly variations of the Caspian sea level and solar activity.

    NASA Astrophysics Data System (ADS)

    Romanchuk, P. R.; Pasechnik, M. N.

    The connection between 11-year cycle of solar activity and the Caspian sea level is investigated. Seasonal changes of the Caspian sea level and annual variations of the sea level with variations of solar activity are studied. The results of the verifications of the sea level forecasts obtained with application of the rules discovered by the authors are given.

  17. 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.

  18. Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

    PubMed

    Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

    2017-08-01

    Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N  (G)-nitro-l-arginine methyl ester (eNOS inhibitor; P<0.05) but not by N-(3-(aminomethyl) bezyl) acetamidine) (inducible nitric oxide synthase inhibitor). STBEV-eNOS catalytic activity was confirmed by visualizing eNOS dimerization. STBEV-eNOS was more abundant in uterine vein compared with peripheral blood, indicating placental origin. STBEV isolated from preeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; P<0.05) and overall lower NO activity (STBMV, not significant; syncytiotrophoblast extracellular exosomes, P<0.05) compared with those from NP. Circulating plasma STBMV from preeclampsia women had lower STBEV-eNOS expression compared with that from NP women (P<0.01). This is the first observation of functional eNOS expressed on STBEV from NP and preeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO

  19. 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…

  20. 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…

  1. Can co-activation reduce kinematic variability? A simulation study.

    PubMed

    Selen, Luc P J; Beek, Peter J; van Dieën, Jaap H

    2005-11-01

    Impedance modulation has been suggested as a means to suppress the effects of internal 'noise' on movement kinematics. We investigated this hypothesis in a neuro-musculo-skeletal model. A prerequisite is that the muscle model produces realistic force variability. We found that standard Hill-type models do not predict realistic force variability in response to variability in stimulation. In contrast, a combined motor-unit pool model and a pool of parallel Hill-type motor units did produce realistic force variability as a function of target force, largely independent of how the force was transduced to the tendon. To test the main hypothesis, two versions of the latter model were simulated as an antagonistic muscle pair, controlling the position of a frictionless hinge joint, with a distal segment having realistic inertia relative to the muscle strength. Increasing the impedance through co-activation resulted in less kinematic variability, except for the lowest levels of co-activation. Model behavior in this region was affected by the noise amplitude and the inertial properties of the model. Our simulations support the idea that muscular co-activation is in principle an effective strategy to meet accuracy demands.

  2. 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

  3. 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…

  4. 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…

  5. Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

    PubMed

    Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

    2016-12-01

    Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

  6. Nitrate reducing activity pervades surface waters during upwelling

    NASA Astrophysics Data System (ADS)

    Fernandes, Sheryl Oliveira; Halarnekar, Reena; Malik, Ashish; Vijayan, Vijitha; Varik, Sandesh; Kumari, Ritu; V. K., Jineesh; Gauns, Manguesh U.; Nair, Shanta; LokaBharathi, P. A.

    2014-09-01

    Nitrate reducing activity (NRA) is known to be mediated by microaerophilic to anaerobic bacteria and generally occurs in the sub-surface waters. However, we hypothesize that NRA could become prominent in the surface waters during upwelling. Hence, we examined nitrification and nitrate reduction along with hydrographic and environmental parameters off Trivandrum and Kochi, south-west-India in June 2010. Shoaling isolines of temperature, density, and nutrients revealed the onset of upwelling off Trivandrum. Shoaling of these signatures was absent in the northern transect off Kochi. The degree of nutrient consumption (DNC) was low emphasizing the presence of newly upwelled water off Trivandrum. A significant increase in NRA (df = 1, p < 0.05) was observed off Trivandrum than at Kochi. Moreover, as hypothesized, NRA at Trivandrum was pronounced at the surface with a maximum rate of 0.85 (± 0.02) μmol L1 h- 1 nearshore which was ~ 29 × higher than that at Kochi. Further, an inverse relationship between NRA and NO3- concentration (n = 34, r = - 0.415, p < 0.01) suggested transformation of the upwelled nutrient. Nitrification/NRA was ~ 10 × lower at 0.28 off Trivandrum indicating a discernible shift towards reduction. Such contribution from bacterial activity could be a response towards restoration of homeostasis.

  7. Reduced maternal and cord nerve growth factor levels in preterm deliveries.

    PubMed

    Dhobale, Madhavi; Mehendale, Savita; Pisal, Hemlata; Nimbargi, Vandana; Joshi, Sadhana

    2012-04-01

    Nerve growth factor (NGF) is a neurotrophin, which exerts an important role in the development and function of the central and peripheral nervous system. There is limited information regarding the levels of NGF during pregnancy and its role in fetal development. We have earlier reported increased oxidative stress in pregnancy complications. The present study examines the levels of NGF in maternal and cord samples in preterm deliveries and its association with oxidative stress marker. A total number of 96 women delivering preterm (<37 weeks gestation) and 94 women delivering at term (control group) (≥37 weeks gestation) were recruited. Plasma NGF levels were measured in both mother and cord plasma using the Emax Immuno Assay System Promega kit. Maternal and cord plasma NGF levels were significantly reduced (p<0.05 for both) in women delivering preterm as compared to term. There was a positive association between maternal and cord plasma NGF levels (p=0.022). Maternal NGF levels were negatively (p=0.017) associated with maternal malondialdehyde (MDA) levels. Reduced cord NGF levels may affect fetal growth in preterm deliveries which may have implications for the neurodevelopmental pathologies in later life. Circulating maternal NGF levels in preterm pregnancies may be a useful marker to predict NGF levels in the neonate.

  8. Reduced autonomic activity during stepwise exposure to high altitude.

    PubMed

    Sevre, K; Bendz, B; Hankø, E; Nakstad, A R; Hauge, A; Kåsin, J I; Lefrandt, J D; Smit, A J; Eide, I; Rostrup, M

    2001-12-01

    Several studies have shown increased sympathetic activity during acute exposure to hypobaric hypoxia. In a recent field study we found reduced plasma catecholamines during the first days after a stepwise ascent to high altitude. In the present study 14 subjects were exposed to a simulated ascent in a hypobaric chamber to test the hypothesis of a temporary reduction in autonomic activity. The altitude was increased stepwise to 4500 m over 3 days. Heart rate variability (HRV) was assessed continuously in seven subjects. Baroreceptor reflex sensitivity (BRS) was determined in eight subjects with the 'Transfer Function' method at baseline, at 4500 m and after returning to baseline. Resting plasma catecholamines and cardiovascular- and plasma catecholamine- responses to cold pressor- (CPT) and mental stress-test (MST) were assessed daily in all and 12 subjects, respectively. Data are mean +/- SEM. Compared with baseline at 4500 m there were lower total power (TP) (35 457 +/- 26 302 vs. 15 001 +/- 11 176 ms2), low frequency (LF) power (3112 +/- 809 vs. 1741 +/- 604 ms2), high frequency (HF) power (1466 +/- 520 vs. 459 +/- 189 ms2) and HF normalized units (46 +/- 0.007 vs. 44 +/- 0.006%), P < or = 0.001. Baroreceptor reflex sensitivity decreased (15.6 +/- 2.1 vs. 9.5 +/- 2.6 ms mmHg(-1), P = 0.015). Resting noradrenaline (NA) decreased (522 +/- 98 vs. 357 +/- 60 pmol L(-1), P = 0.027). The increase in systolic blood pressure (SBP) and NA during mental stress was less pronounced (21 +/- 4 vs. 10 +/- 2% and 25 +/- 9 vs. -2 +/- 8%, respectively, P < 0.05). The increase in SBP during cold pressor test decreased (16 +/- 3 vs. 1 +/- 6%, P = 0.03). Diastolic blood pressure, HR and adrenaline displayed similar tendencies. We conclude that a transient reduction in parasympathetic and sympathetic activity was demonstrated during stepwise exposure to high altitude.

  9. Promoting physical activity and reducing climate change: opportunities to replace short car trips with active transportation.

    PubMed

    Maibach, Edward; Steg, Linda; Anable, Jillian

    2009-10-01

    Automobile use is a significant contributor to climate change, local air pollution, pedestrian injuries and deaths, declines in physical activity and obesity. A significant proportion of car use is for short trips that can relatively easily be taken with active transportation options--walking or cycling--or with public transportation. In this commentary, we review a number of immediate, practical opportunities to implement policies and programs that reduce short car trips and increase active transportation.

  10. Modulation of ABCA1 by an LXR Agonist Reduces Beta-Amyloid Levels and Improves Outcome after Traumatic Brain Injury

    PubMed Central

    Loane, David J.; Washington, Patricia M.; Vardanian, Lilit; Pocivavsek, Ana; Hoe, Hyang-Sook; Duff, Karen E.; Cernak, Ibolja; Rebeck, G. William; Faden, Alan I.

    2011-01-01

    Abstract Traumatic brain injury (TBI) increases brain beta-amyloid (Aβ) in humans and animals. Although the role of Aβ in the injury cascade is unknown, multiple preclinical studies have demonstrated a correlation between reduced Aβ and improved outcome. Therefore, therapeutic strategies that enhance Aβ clearance may be beneficial after TBI. Increased levels of ATP-binding cassette A1 (ABCA1) transporters can enhance Aβ clearance through an apolipoprotein E (apoE)-mediated pathway. By measuring Aβ and ABCA1 after experimental TBI in C57BL/6J mice, we found that Aβ peaked early after injury (1–3 days), whereas ABCA1 had a delayed response (beginning at 3 days). As ABCA1 levels increased, Aβ levels returned to baseline levels—consistent with the known role of ABCA1 in Aβ clearance. To test if enhancing ABCA1 levels could block TBI-induced Aβ, we treated TBI mice with the liver X-receptor (LXR) agonist T0901317. Pre- and post-injury treatment increased ABCA1 levels at 24 h post-injury, and reduced the TBI-induced increase in Aβ. This reduction in Aβ was not due to decreased amyloid precursor protein processing, or a shift in the solubility of Aβ, indicating enhanced clearance. T0901317 also limited motor coordination deficits in injured mice and reduced brain lesion volume. These data indicate that activation of LXR can reduce Aβ accumulation after TBI, and is accompanied by improved functional recovery. PMID:21175399

  11. 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

  12. Levels of atherogenic lipoproteins are unexpectedly reduced in interstitial fluid from type 2 diabetes patients.

    PubMed

    Apro, Johanna; Parini, Paolo; Broijersén, Anders; Angelin, Bo; Rudling, Mats

    2015-08-01

    At a given level of serum cholesterol, patients with T2D have an increased risk of developing atherosclerosis compared with nondiabetic subjects. We hypothesized that T2D patients have an increased interstitial fluid (IF)-to-serum gradient ratio for LDL, due to leakage over the vascular wall. Therefore, lipoprotein profiles in serum and IF from 35 T2D patients and 35 healthy controls were assayed using fast performance liquid chromatography. The IF-to-serum gradients for VLDL and LDL cholesterol, as well as for apoB, were clearly reduced in T2D patients compared with healthy controls. No such differences were observed for HDL cholesterol. Contrary to our hypothesis, the atherogenic VLDL and LDL particles were not increased in IF from diabetic patients. Instead, they were relatively sparser than in healthy controls. The most probable explanation to our unexpected finding is that these lipoproteins are more susceptible to retainment in the extravascular space of these patients, reflecting a more active uptake by, or adhesion to, tissue cells, including macrophages in the vascular wall. Further studies are warranted to further characterize the mechanisms underlying these observations, which may be highly relevant for the understanding of why the propensity to develop atherosclerosis is increased in T2D. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

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

    PubMed

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

    2015-06-01

    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.

  14. 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

  15. Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness.

    PubMed

    Watling, Christopher N; Smith, Simon S; Horswill, Mark S

    2014-11-01

    The purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15-min nap break or a 15-min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break.

  16. Free 25-hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxyvitamin D levels.

    PubMed Central

    Bikle, D D; Halloran, B P; Gee, E; Ryzen, E; Haddad, J G

    1986-01-01

    We determined the free fraction of 25-dihydroxyvitamin D (25OHD) in the serum of subjects with clinical evidence of liver disease and correlated these measurements to the levels of vitamin D binding protein and albumin. These subjects when compared to normal individuals had lower total 25OHD levels, higher percent free 25OHD levels, but equivalent free 25OHD levels. These subjects also had reduced vitamin D binding protein and albumin concentrations. The total concentration of 25OHD correlated positively with both vitamin D binding protein and albumin, whereas the percent free 25OHD correlated negatively with vitamin D binding protein and albumin. The free 25OHD levels did not correlate with either vitamin D binding protein or albumin. We conclude that total vitamin D metabolite measurements may be misleading in the evaluation of the vitamin D status of patients with liver disease, and recommend that free 25OHD levels also be determined before making a diagnosis of vitamin D deficiency. PMID:3745436

  17. A multi coding technique to reduce transition activity in VLSI circuits

    NASA Astrophysics Data System (ADS)

    Vithyalakshmi, N.; Rajaram, M.

    2014-02-01

    Advances in VLSI technology have enabled the implementation of complex digital circuits in a single chip, reducing system size and power consumption. In deep submicron low power CMOS VLSI design, the main cause of energy dissipation is charging and discharging of internal node capacitances due to transition activity. Transition activity is one of the major factors that also affect the dynamic power dissipation. This paper proposes power reduction analyzed through algorithm and logic circuit levels. In algorithm level the key aspect of reducing power dissipation is by minimizing transition activity and is achieved by introducing a data coding technique. So a novel multi coding technique is introduced to improve the efficiency of transition activity up to 52.3% on the bus lines, which will automatically reduce the dynamic power dissipation. In addition, 1 bit full adders are introduced in the Hamming distance estimator block, which reduces the device count. This coding method is implemented using Verilog HDL. The overall performance is analyzed by using Modelsim and Xilinx Tools. In total 38.2% power saving capability is achieved compared to other existing methods.

  18. Evaluation of methods to reduce formaldehyde levels of cadavers in the dissection laboratory.

    PubMed

    Whitehead, Mark C; Savoia, Maria C

    2008-01-01

    Dissection of conventionally embalmed cadavers exposes students, staff, and faculty to formaldehyde, a probable carcinogen. Therefore, prudent practices should seek to minimize formaldehyde exposure. In this study, we evaluated two commercially available chemicals, InfuTrace and Perfect Solution, for their effectiveness in reducing ambient formaldehyde levels. Four cadavers embalmed conventionally with formaldehyde and/or with the above agents were compared for their formaldehyde levels under conditions that strictly controlled for air circulation and for locations and methods of testing, and during activities that simulated student dissecting. For InfuTrace, one cadaver was reinfused with InfuTrace after initial standard perfusion with formaldehyde; a second cadaver had InfuTrace injected into the thoracic and abdominal body cavities after formaldehyde perfusion. For Perfect Solution, the product was used for embalming a third cadaver in lieu of formaldehyde. For a control, a fourth cadaver was embalmed with the standard formaldehyde solution. Testing of personal and ambient room air samples and of fluid obtained from the cadavers was performed and analyzed in a blinded fashion. Results indicated that both Perfect Solution, substituted for standard formaldehyde embalming, and InfuTrace infused through the vasculature after formaldehyde embalming, resulted in lower concentrations of formaldehyde than embalming with formaldehyde solution alone or in combination with body cavity injection of InfuTrace. These differences in formaldehyde concentrations are consistent across measuring methods, for example, of room air, of breathing zone air during cadaver handling and dissection, and of liquid samples obtained from the cadavers. Perfect Solution yielded suboptimum fixation and a different texture, color, and smell than the formaldehyde treatments. (c) 2007 Wiley-Liss, Inc.

  19. Reduced levels of Cacna1c attenuate mesolimbic dopamine system function.

    PubMed

    Terrillion, C E; Dao, D T; Cachope, R; Lobo, M K; Puche, A C; Cheer, J F; Gould, T D

    2017-06-01

    Genetic variation in CACNA1C, which codes for the L-type calcium channel (LTCC) Cav 1.2, is associated with clinical diagnoses of bipolar disorder, depression and schizophrenia. Dysregulation of the mesolimbic-dopamine (ML-DA) system is linked to these syndromes and LTCCs are required for normal DAergic neurotransmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc). It is unclear, however, how variations in CACNA1C genotype, and potential subsequent changes in expression levels in these regions, modify risk. Using constitutive and conditional knockout mice, and treatment with the LTCC antagonist nimodipine, we examined the role of Cacna1c in DA-mediated behaviors elicited by psychomotor stimulants. Using fast-scan cyclic voltammetry, DA release and reuptake in the NAc were measured. We find that subsecond DA release in Cacna1c haploinsufficient mice lacks normal sensitivity to inhibition of the DA transporter (DAT). Constitutive haploinsufficiency of Cacna1c led to attenuation of hyperlocomotion following acute administration of stimulants specific to DAT, and locomotor sensitization of these mice to the DAT antagonist GBR12909 did not reach the same level as wild-type mice. The maintenance of sensitization to GBR12909 was attenuated by administration of nimodipine. Sensitization to GBR12909 was attenuated in mice with reduced Cacna1c selectively in the VTA but not in the NAc. Our findings show that Cacna1c is crucial for normal behavioral responses to DA stimulants and that its activity in the VTA is required for behavioral sensitization. Cacna1c likely exerts these effects through modifications to presynaptic ML-DA system function. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  20. Creating a Culture of Safety by Reducing Noise Levels in the OR.

    PubMed

    Hogan, Lisa J; Harvey, Renee L

    2015-10-01

    We implemented a quality improvement project to reduce noise levels in the OR in response to complaints from the anesthesia staff members at two community hospitals. Excessive noise has been shown to increase staff member stress, fatigue, distraction, and ineffective communication, which can lead to medical errors. We measured noise levels during anesthesia induction and emergence for 118 different surgical procedures and compared noise levels before and after the improvement project intervention. Staff member education and noise reduction strategies, which included signage, prominent noise meters, and specific suggestions to staff members, helped to significantly reduce the noise level during the anesthetic induction and emergence phases of OR procedures. Copyright © 2015 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  1. Chronic ethanol perturbs testicular folate metabolism and dietary folate deficiency reduces sex hormone levels in the Yucatan micropig.

    PubMed

    Wallock-Montelius, Lynn M; Villanueva, Jesus A; Chapin, Robert E; Conley, A J; Nguyen, Hung P; Ames, Bruce N; Halsted, Charles H

    2007-03-01

    Although alcoholism causes changes in hepatic folate metabolism that are aggravated by folate deficiency, male reproductive effects have never been studied. We evaluated changes in folate metabolism in the male reproductive system following chronic ethanol consumption and folate deficiency. Twenty-four juvenile micropigs received folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE or FDE) for 14 wk, and the differences between the groups were determined by ANOVA. Chronic ethanol consumption (FSE and FDE compared with FS and FD groups) reduced testis and epididymis weights, testis sperm concentrations, and total sperm counts and circulating FSH levels. Folate deficiency (FD and FDE compared with FS and FSE groups) reduced circulating testosterone, estradiol and LH levels, and also testicular 17,20-lyase and aromatase activities. There was histological evidence of testicular lesions and incomplete progression of spermatogenesis in all treated groups relative to the FS control, with the FDE group being the most affected. Chronic ethanol consumption increased testis folate concentrations and decreased testis methionine synthase activity, whereas folate deficiency reduced total testis folate levels and increased methionine synthase activity. In all pigs combined, testicular methionine synthase activity was negatively associated with circulating estradiol, LH and FSH, and 17,20-lyase activity after controlling for ethanol, folate deficiency, and their interaction. Thus, while chronic ethanol consumption primarily impairs spermatogenesis, folate deficiency reduces sex hormones, and the two treatments have opposite effects on testicular folate metabolism. Furthermore, methionine synthase may influence the hormonal regulation of spermatogenesis.

  2. 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.

  3. 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

  4. Inhibition of gamma-secretase activity reduces Abeta production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease.

    PubMed

    Sheng, Baiyang; Gong, Kai; Niu, Ying; Liu, Lingling; Yan, Yufang; Lu, Guangyuan; Zhang, Lihai; Hu, Min; Zhao, Nanming; Zhang, Xiufang; Tang, Peifu; Gong, Yandao

    2009-05-15

    It has been argued that gamma-secretase should be considered as a pharmacological target, as there are few mechanism-based experimental and clinical studies on gamma-secretase treatment. In this study, we found that N2a cells bearing APP695 or its Swedish mutant exhibited increased basal levels of ROS, nitric oxide (NO), protein carbonyls, MDA and intracellular calcium, as well as reduced level of the mitochondrial membrane potential and ATP. When the activity of gamma-secretase was inhibited by expression of the D385A PS1 variant, cells (N2a/Swe.D385A) showed reduced basal levels of ROS, nitric oxide (NO), protein carbonyls, MDA and intracellular calcium, as well as increased mitochondrial membrane potential and ATP level. In addition, N2a/Swe.D385A cells showed reduced vulnerability to H(2)O(2)-induced apoptosis. The Bcl-2 and JNK/ERK pathways were proven to be involved in the change of vulnerability to H(2)O(2)-induced apoptosis. Moreover, we discovered that inhibition of gamma-secretase by DAPT would lead to a reduction of ROS levels and stabilization of mitochondrial function in APP (N2a/APP695) and APP Swedish mutant (N2a/APPswe) transfected cells. At last, it was shown that Abeta antibody and antiserum prevented increase of ROS and reduction of mitochondrial membrane potential in N2a/Swe.DeltaE9 cells but not in N2a/Swe.D385A cells, which indicated that reduced formation of Abeta was the reason for reduction of ROS formation and increase of mitochondrial membrane potential when PS-1 activity was impaired in N2a/Swe.D385A cells. We concluded that neurotoxicity was positively correlated with the activity of gamma-secretase, which suggested inhibition of gamma-secretase is a rational pharmacological target for Alzheimer's disease treatment.

  5. Sound-Level Measurements of a Light Airplane Modified to Reduce Noise Reaching the Ground

    NASA Technical Reports Server (NTRS)

    Vogeley, A W

    1949-01-01

    An Army liaison-type airplane, representative of personal airplanes in the 150 to 200 horsepower class, has been modified to reduce propeller and engine noise according to known principles of airplane-noise reduction. Noise-level measurements demonstrate that, with reference to an observer on the ground, a noisy airplane of this class can be made quiet -- perhaps more quiet than necessary. In order to avoid extreme and unnecessary modifications, acceptable noise levels must be determined.

  6. Modification of activity level through biofeedback and operant conditioning.

    PubMed Central

    Schulman, J L; Stevens, T M; Suran, B G; Kupst, M J; Naughton, M J

    1978-01-01

    The biomotometer, an electronic device that simultaneously measures activity and provides auditory feedback to the subject, was used in combination with material reinforcers in two experiments attempting to modify activity level in children. In the first study the activity level of an 11-year-old highly active boy was decreased below mean baseline during conditioning in a classroom setting. His level of activity returned to baseline when feedback was withdrawn. In the second study, activity level of a 10-year-old hypoactive boy was increased over mean baseline level during conditioning in a free-play setting, and returned to slightly below baseline during five extinction trials. Results of these studies indicate that the biomotometer is a useful instrument for modification of activity level. PMID:649522

  7. Exogenous folate ameliorates ethanol-induced brain hyperhomocysteinemia and exogenous ethanol reduces taurine levels in chick embryos.

    PubMed

    Barnett, Robert K; Booms, Stephanie L; Gura, Tracy; Gushrowski, Mara; Miller, Robert R

    2009-07-01

    The effects of exogenous ethanol and/or folic acid on endogenous homocysteine (HoCys) and SAM (S-adenosylmethionine)/SAH (S-adenosylhomocysteine) levels in chick brains were studied at 11 days of development. Embryonic EtOH (3.0 mmol/kg egg) exposure caused a 1.6-fold increase in brain HoCys levels and a 9-fold decrease in brain SAM/SAH levels as compared to controls (plevels returned to control values when injected with a mixture of EtOH and folic acid (3.0 mmol EtOH/kg egg and 34 mumol folic acid/kg egg). The effects of exogenous EtOH on the remethylation pathway, as measured by 10-formyltetrahydrofolate dehydrogenase (10-FTHF DH) activities, and the transsulfuration pathway, as measured by taurine levels, were studied at 18 days of development. A single dosage of EtOH (3.0 mmol/kg egg; E(0)) and two daily dosages of EtOH (E(0-1)) failed to influence brain and hepatic 10-FTHF DH activities when compared to controls. However, three daily dosages of EtOH (E(0-2)) caused approximately a two-fold increase in brain 10-FTHF DH activities and a three-fold increase in hepatic 10-FTHF DH activities as compared to controls (preduced taurine levels in both brain and hepatic tissues (preduced hepatic taurine levels as compared to controls (p

  8. Cathepsin D levels are reduced in patients with preeclampsia in Korean population.

    PubMed

    Kim, Ho Yeon; Lee, Maria; Kang, Hye Won; Moon, ChongSoo

    2013-12-01

    To compare the circulating levels of cathepsin D in preeclamptic and normotensive pregnancies. Fifty pregnant and 20 healthy non-pregnant patients were enrolled in this study. Of the 50 pregnant patients, 15 were preeclamptic and 35 patients were normotensive. Serum levels of soluble cathepsin D were measured with an enzyme-linked immunosorbent assay (ELISA) kit. Cathepsin D levels were significantly lower in preeclamptic patients than normotensive pregnant patients (p=0.033). The serum levels of cathepsin D in preeclamptic and non-pregnant healthy patients showed similar results. The serum levels of cathepsin D were not positively correlated with preeclampsia severity or the incidence of delivery of small for gestational age infants. We conclude that a reduced cathepsin D level is an important factor that may contribute to the pathogenesis of preeclampsia, possibly by inhibiting normal trophoblastic invasion. These results contribute to the understanding of this serious obstetric problem. © 2013. Published by Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

  11. Physical activity levels in the treatment of juvenile fibromyalgia.

    PubMed

    Sherry, David D

    2013-01-01

    Physical activity is paramount in the treatment of juvenile fibromyalgia, although some interventions use indirect methods to increase activity levels rather than address physical dysfunction head-on. New research explores the effects of a psychotherapeutic approach on levels of physical activity in adolescents with fibromyalgia.

  12. Multi-Level Reduced Order Modeling Equipped with Probabilistic Error Bounds

    NASA Astrophysics Data System (ADS)

    Abdo, Mohammad Gamal Mohammad Mostafa

    model parameters, responses, or state variables, are projected onto lower dimensional subspaces, referred to as the "active subspaces", which are selected to capture a user-defined portion of the snapshots variations. Once determined, the ROM model application involves constraining the variables to the active subspaces. In doing so, the contribution from the variables discarded components can be estimated using a fundamental theorem from random matrix theory which has its roots in Dixon's theory, developed in 1983. This theory was initially presented for linear matrix operators. The thesis extends this theorem's results to allow reduction of general smooth nonlinear operators. The result is an approach by which the adequacy of a given active subspace determined using a given set of snapshots, generated either using the full high fidelity model, or other models with lower fidelity, can be assessed, which provides insight to the analyst on the type of snapshots required to reach a reduction that can satisfy user-defined preset tolerance limits on the reduction errors. Reactor physics calculations are employed as a test bed for the proposed developments. The focus will be on reducing the effective dimensionality of the various data streams such as the cross-section data and the neutron flux. The developed methods will be applied to representative assembly level calculations, where the size of the cross-section and flux spaces are typically large, as required by downstream core calculations, in order to capture the broad range of conditions expected during reactor operation. (Abstract shortened by ProQuest.).

  13. Mercury Reduces the Enzymatic Activity of Neprilysin in Differentiated SH-SY5Y Cells

    PubMed Central

    Chin-Chan, Miguel; Segovia, José; Quintanar, Liliana; Arcos-López, Trinidad; Hersh, Louis B.; Chow, K. Martin; Rodgers, David W.; Quintanilla-Vega, Betzabet

    2015-01-01

    Levels of amyloid beta (Aβ) in the central nervous system are regulated by the balance between its synthesis and degradation. Neprilysin (NEP) is associated with Alzheimer’s disease (AD) by its ability to degrade Aβ. Some studies have involved the exposure to mercury (Hg) in AD pathogenesis; therefore, our aim was to investigate the effects on the anabolism and catabolism of Aβ in differentiated SH-SY5Y cells incubated with 1–20 μM of Hg. Exposure to 20 µM of Hg induced an increase in Aβ-42 secretion, but did not increase the expression of the amyloid precursor protein (APP). Hg incubation (10 and 20 µM) increased NEP protein levels; however, it did not change NEP mRNA levels nor the levels of the amyloid intracellular domain peptide, a protein fragment with transcriptional activity. Interestingly, Hg reduced NEP activity at 10 and 20 µM, and circular dichroism analysis using human recombinant NEP showed conformational changes after incubation with molar equivalents of Hg. This suggests that the Hg-induced inhibition of NEP activity may be mediated by a conformational change resulting in reduced Aβ-42 degradation. Finally, the comparative effects of lead (Pb, 50 μM) were evaluated. We found a significant increase in Aβ-42 levels and a dramatic increase in APP protein levels; however, no alteration in NEP levels was observed nor in the enzymatic activity of this metalloprotease, despite the fact that Pb slightly modified the rhNEP conformation. Overall, our data suggest that Hg and Pb increase Aβ levels by different mechanisms. PMID:25673500

  14. Mercury Reduces the Enzymatic Activity of Neprilysin in Differentiated SH-SY5Y Cells.

    PubMed

    Chin-Chan, Miguel; Segovia, José; Quintanar, Liliana; Arcos-López, Trinidad; Hersh, Louis B; Chow, K Martin; Rodgers, David W; Quintanilla-Vega, Betzabet

    2015-05-01

    Levels of amyloid beta (Aβ) in the central nervous system are regulated by the balance between its synthesis and degradation. Neprilysin (NEP) is associated with Alzheimer's disease (AD) by its ability to degrade Aβ. Some studies have involved the exposure to mercury (Hg) in AD pathogenesis; therefore, our aim was to investigate the effects on the anabolism and catabolism of Aβ in differentiated SH-SY5Y cells incubated with 1-20 μM of Hg. Exposure to 20 µM of Hg induced an increase in Aβ-42 secretion, but did not increase the expression of the amyloid precursor protein (APP). Hg incubation (10 and 20 µM) increased NEP protein levels; however, it did not change NEP mRNA levels nor the levels of the amyloid intracellular domain peptide, a protein fragment with transcriptional activity. Interestingly, Hg reduced NEP activity at 10 and 20 µM, and circular dichroism analysis using human recombinant NEP showed conformational changes after incubation with molar equivalents of Hg. This suggests that the Hg-induced inhibition of NEP activity may be mediated by a conformational change resulting in reduced Aβ-42 degradation. Finally, the comparative effects of lead (Pb, 50 μM) were evaluated. We found a significant increase in Aβ-42 levels and a dramatic increase in APP protein levels; however, no alteration in NEP levels was observed nor in the enzymatic activity of this metalloprotease, despite the fact that Pb slightly modified the rhNEP conformation. Overall, our data suggest that Hg and Pb increase Aβ levels by different mechanisms.

  15. 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…

  16. Inquiry Based Method: A Case Study to Reduce Levels of Resistance

    ERIC Educational Resources Information Center

    Mthethwa-Sommers, Shirley

    2010-01-01

    This article is based on a case study exploring the effectiveness of inquiry-based method of teaching to reduce levels of student resistance to diversity issues and increase students' willingness to become activists. The case study draws from a one-year action research conducted in a Foundations of Education class. Data were collected through…

  17. 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…

  18. Reduced heme levels underlie the exponential growth defect of the Shewanella oneidensis hfq mutant.

    PubMed

    Brennan, Christopher M; Mazzucca, Nicholas Q; Mezoian, Taylor; Hunt, Taylor M; Keane, Meaghan L; Leonard, Jessica N; Scola, Shelby E; Beer, Emma N; Perdue, Sarah; Pellock, Brett J

    2014-01-01

    The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA) function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA), the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step.

  19. 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…

  20. 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…

  1. Reduced Heme Levels Underlie the Exponential Growth Defect of the Shewanella oneidensis hfq Mutant

    PubMed Central

    Mezoian, Taylor; Hunt, Taylor M.; Keane, Meaghan L.; Leonard, Jessica N.; Scola, Shelby E.; Beer, Emma N.; Perdue, Sarah; Pellock, Brett J.

    2014-01-01

    The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA) function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA), the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step. PMID:25356668

  2. 8-Iso-prostaglandin f(2alpha) reduces trophoblast invasion and matrix metalloproteinase activity.

    PubMed

    Staff, A C; Ranheim, T; Henriksen, T; Halvorsen, B

    2000-06-01

    Preeclampsia is a common pregnancy complication in the latter half of gestation diagnosed by hypertension and proteinuria. A key feature of preeclampsia is an altered placentation with reduced trophoblast invasion. Normal placentation requires controlled invasion of trophoblasts into the maternal uterine wall, with secretion of specific proteolytic enzymes able to degrade basement membranes and extracellular matrix, such as the matrix metalloproteinases (MMPs). 8-Iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo and is biologically active. We have recently reported an elevated content of free 8-iso-PGF(2alpha) in preeclamptic gestational tissue at delivery. Assuming an elevated level of 8-iso-PGF(2alpha) during the invasion period of the pregnancy, we hypothesized that 8-iso-PGF(2alpha) could reduce invasion of JAR cells, a choriocarcinoma cell line. We investigated JAR cell invasion with 2 types of Transwell assays and demonstrated that 8-iso-PGF(2alpha) (10 micromol/L) resulted in reduced cell invasion in both the colorimetric and radioactivity Transwell assays (P<0.01). Zymograms revealed reduced MMP-2 and MMP-9 activity in conditioned media from JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) (P<0.02). 8-Iso-PGF(2alpha) (10 micromol/L) also reduced the collagenase type IV activity in the conditioned media of JAR cells (P=0.04). No effects on MMP-2 and MMP-9 mRNA levels were observed after incubation with 8-iso-PGF(2alpha) (10 micromol/L), whereas protein levels were significantly decreased (P<0.02), suggesting a posttranscriptional regulation. We hypothesize a potential role for 8-iso-PGF(2alpha) in the reduced trophoblast invasion in preeclampsia.

  3. Offshore suspension relaying to reduce levels of Vibrio vulnificus in oysters (Crassostrea virginica).

    PubMed Central

    Motes, M L; DePaola, A

    1996-01-01

    Oysters naturally contaminated with 10(3) to 10(4) most probable numbers (MPN) of Vibrio vulnificus per g were relayed to offshore waters (salinity, 30 to 34 ppt), where they were suspended in racks at a depth of 7.6 m. V. vulnificus counts in oysters were reduced to < 10 MPN/g within 7 to 17 days in five of the six studies. At the end of the studies (17 to 49 days), V. vulnificus levels were reduced further and ranged from a mean of 0.23 to 2.6 MPN/g. Oyster mortalities during relaying were < 6%. The reduction of V. vulnificus in relayed oysters is associated with exposure to high-salinity environments essentially devoid of V. vulnificus. Offshore suspension relaying may be a method that industry can employ to reduce V. vulnificus levels in raw Gulf Coast oysters. PMID:8837445

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

    PubMed

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

    2016-03-01

    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. Using the New York City (NYC) 2009 YRBS, we created school-level poverty quartiles to append to individual YRBS records by ranking schools by %FRPM. We compared this with 2 other school-level poverty measures using students' home and school neighborhood-level poverty and measured the association of these 3 school-level proxies with individual's household income. Last, we evaluated health outcomes by race/ethnicity and poverty to demonstrate the importance of accounting for poverty. The school-level measure that used %FRPM had the strongest association with household income. When the school-level individual poverty proxy was included in illustrative analyses using YRBS data, patterns by poverty within race/ethnicity emerged that were not seen when looking at race/ethnicity alone. Using a poverty measure to analyze school-based data will provide a better understanding of the impact of SES on health outcomes. Based on our evaluation, when individual-level information is not available, we propose using school-level %FRPM, which are publicly available throughout the United States. © 2016, American School Health Association.

  5. Effect of reduced water activity and reduced matric potential on the germination of xerophilic and non-xerophilic fungi.

    PubMed

    Huang, Yang; Begum, Mariam; Chapman, Belinda; Hocking, Ailsa D

    2010-05-30

    Reduction in water activity (a(w)) is used as a microbiological hurdle to prevent food spoilage. To minimize the levels of salt and sugar, which are commonly used to reduce a(w), the potential of food structure as a microbiological hurdle needs to be assessed. The concept of matric potential (Psi(m)) is used to measure the effect of food structure on water movement. This study reports the effect of reduced a(w) and reduced Psi(m) on the germination of xerophilic fungi (represented by Eurotium herbariorum) and non-xerophilic fungi (represented by Aspergillus niger) on model glycerol agar media. Germination curves were plotted with the percentage of germinated spores against time. The germination time (t(G)), which is defined as the time at which 50% of the total viable spores have germinated, was estimated using the Gompertz model. Total viable spores was defined as those spores that were able to germinate under the optimum a(w) and Psi(m) conditions for each species, i.e. 0.95 a(w) and 2.5% agar for E. herbariorum and 0.98 a(w) and 2.5% agar for A. niger. As a(w) decreased from 0.90 to 0.85 a(w), t(G) increased significantly for both the xerophilic fungi and non-xerophilic species at equivalent matric potential values. When matric potential was reduced from -12 kPa (2.5% agar) to -38 kPa (12.5% agar), t(G) of A. niger was significantly extended at 0.90 a(w); however, t(G) remained the same for A. niger at 0.85 a(w), and for E. herbariorum at 0.80, 0.85 and 0.90 a(w). This study demonstrated that the germination time for non-xerophilic and xerophilic fungi was extended by reduced a(w), however the effect of reduced Psi(m) was limited. (c) 2010. Published by Elsevier B.V. All rights reserved.

  6. 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

  7. Predicting bone remodeling around tissue- and bone-level dental implants used in reduced bone width.

    PubMed

    Eser, Atilim; Tonuk, Ergin; Akca, Kivanc; Dard, Michel M; Cehreli, Murat Cavit

    2013-09-03

    The objective of this study was to predict time-dependent bone remodeling around tissue- and bone-level dental implants used in patients with reduced bone width. The remodeling of bone around titanium tissue-level, and titanium and titanium-zirconium alloy bone-level implants was studied under 100 N oblique load for one month by implementing the Stanford theory into three-dimensional finite element models. Maximum principal stress, minimum principal stress, and strain energy density in peri-implant bone and displacement in x- and y- axes of the implant were evaluated. Maximum and minimum principal stresses around tissue-level implant were higher than bone-level implants and both bone-level implants experienced comparable stresses. Total strain energy density in bone around titanium implants slightly decreased during the first two weeks of loading followed by a recovery, and the titanium-zirconium implant showed minor changes in the axial plane. Total strain energy density changes in the loading and contralateral sides were higher in tissue-level implant than other implants in the cortical bone at the horizontal plane. The displacement values of the implants were almost constant over time. Tissue-level implants were associated with higher stresses than bone-level implants. The time-dependent biomechanical outcome of titanium-zirconium alloy bone-level implant was comparable to the titanium implant. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Contactin-1 reduces E-cadherin expression via activating AKT in lung cancer.

    PubMed

    Yan, Judy; Wong, Nicholas; Hung, Claudia; Chen, Wendy Xin-Yi; Tang, Damu

    2013-01-01

    Contactin-1 has been shown to promote cancer metastasis. However, the underlying mechanisms remain unclear. We report here that knockdown of contactin-1 in A549 lung cancer cells reduced A549 cell invasion and the cell's ability to grow in soft agar without affecting cell proliferation. Reduction of contactin-1 resulted in upregulation of E-cadherin, consistent with E-cadherin being inhibitive of cancer cell invasion. In an effort to investigate the mechanisms whereby contactin-1 reduces E-cadherin expression, we observed that contactin-1 plays a role in AKT activation, as knockdown of contactin-1 attenuated AKT activation. Additionally, inhibition of AKT activation significantly enhanced E-cadherin expression, an observation that mimics the situation observed in contactin-1 knockdown, suggesting that activation of AKT plays a role in contactin-1-mediated downregulation of E-cadherin. In addition, we were able to show that knockdown of contactin-1 did not further reduce A549 cell's invasion ability, when AKT activation was inhibited by an AKT inhibitor. To further support our findings, we overexpressed CNTN-1 in two CNTN-1 null breast cancer cell lines expressing E-cadherin. Upon overexpression, CNTN-1 reduced E-cadherin levels in one cell line and increased AKT activation in the other. Furthermore, in our study of 63 primary lung cancers, we observed 65% of primary lung cancers being contactin-1 positive and in these carcinomas, 61% were E-cadherin negative. Collectively, we provide evidence that contactin-1 plays a role in the downregulation of E-cadherin in lung cancer and that AKT activation contributes to this process. In a study of mechanisms responsible for contactin-1 to activate AKT, we demonstrated that knockdown of CNTN-1 in A549 cells did not enhance PTEN expression but upregulated PHLPP2, a phosphatase that dephosphorylates AKT. These observations thus suggest that contactin-1 enhances AKT activation in part by preventing PHLPP2-mediated AKT

  9. Effect of self-glazing on reducing the radioactivity levels of red mud based ceramic materials.

    PubMed

    Qin, Shuo; Wu, Bolin

    2011-12-30

    Self-glazing red mud based ceramic materials (RMCM) were produced by normal pressure sintering process using the main raw materials of red mud. The properties of the RMCM samples were investigated by the measurements of mechanical properties, radiation measurement, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results show that the self-glazing RMCM have good mechanical properties (water absorption and apparent porosity approached zero; bulk density, 2.94 g/cm(3); compressive strength, 78.12 MPa). The radiation level has clear change regularity that the radioactivity levels of red mud (6360 Bq) is obvious declined, and can be reduced to that of the natural radioactive background of Guilin Karst landform, China (3600 Bq). It will not only consume large quantities of red mud, but also decrease the production cost of self-glazing RMCM. And the statement of this paper will offer effective ways to reduce the radioactivity level of red mud.

  10. Restricted cell elongation in Arabidopsis hypocotyls is associated with a reduced average pectin esterification level

    PubMed Central

    Derbyshire, Paul; McCann, Maureen C; Roberts, Keith

    2007-01-01

    Background Cell elongation is mainly limited by the extensibility of the cell wall. Dicotyledonous primary (growing) cell walls contain cellulose, xyloglucan, pectin and proteins, but little is known about how each polymer class contributes to the cell wall mechanical properties that control extensibility. Results We present evidence that the degree of pectin methyl-esterification (DE%) limits cell growth, and that a minimum level of about 60% DE is required for normal cell elongation in Arabidopsis hypocotyls. When the average DE% falls below this level, as in two gibberellic acid (GA) mutants ga1-3 and gai, and plants expressing pectin methyl-esterase (PME1) from Aspergillus aculeatus, then hypocotyl elongation is reduced. Conclusion Low average levels of pectin DE% are associated with reduced cell elongation, implicating PMEs, the enzymes that regulate DE%, in the cell elongation process and in responses to GA. At high average DE% other components of the cell wall limit GA-induced growth. PMID:17572910

  11. Prenatal androgen exposure and children's aggressive behavior and activity level.

    PubMed

    Spencer, Debra; Pasterski, Vickie; Neufeld, Sharon; Glover, Vivette; O'Connor, Thomas G; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L; Hines, Melissa

    2017-09-19

    Some human behaviors, including aggression and activity level, differ on average for males and females. Here we report findings from two studies investigating possible relations between prenatal androgen and children's aggression and activity level. For study 1, aggression and activity level scores for 43 girls and 38 boys, aged 4 to 11years, with congenital adrenal hyperplasia (CAH, a genetic condition causing increased adrenal androgen production beginning prenatally) were compared to those of similarly-aged, unaffected relatives (41 girls, 31 boys). Girls with CAH scored higher on aggression than unaffected girls, d=0.69, and unaffected boys scored higher on activity level than unaffected girls, d=0.50. No other group differences were significant. For study 2, the relationship of amniotic fluid testosterone to aggression and activity level was investigated in typically-developing children (48 girls, 44 boys), aged 3 to 5years. Boys scored higher than girls on aggression, d=0.41, and activity level, d=0.50. However, amniotic fluid testosterone was not a significant predictor of aggression or activity level for either sex. The results of the two studies provide some support for an influence of prenatal androgen exposure on children's aggressive behavior, but not activity level. The within-sex variation in amniotic fluid testosterone may not be sufficient to allow reliable assessment of relations to aggression or activity level. Copyright © 2017. Published by Elsevier Inc.

  12. Lost in distractors: Reduced Autobiographical Memory Specificity and dispersed activation spreading over distractors in working memory.

    PubMed

    Takano, Keisuke; Moriya, Jun; Raes, Filip

    2017-07-01

    Studies on autobiographical memory retrieval highlight the prominence of rapid and direct access to a specific event memory. Because it has been believed that autobiographical memory retrieval mostly relies on an effortful generative process, there is little empirical evidence on the early stage of information processing that contributes to autobiographical memory specificity (AMS). Therefore, we investigated the associations between AMS and automatic activation of information stimulated by rapid presentation of emotional words. Study 1 involved a visual search task to assess activation of various distractors in working memory. Participants with reduced AMS showed a tendency to activate distractors that were not semantically associated with preceding cues. In Study 2, we manipulated the levels of AMS by using a computerized version of Memory Specificity Training (c-MeST) to observe the changes in the activation of distractors. Results showed that increases in AMS were associated with decreases in activation of cue-unassociated distractors. These findings suggest that reduced AMS can be characterized by dispersed activation spreading over semantically unassociated distractors in automatic information selection of working memory. Because we also found an association between depressive symptoms and AMS, the role of automatic information processing in the relation between reduced AMS and depression is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

    PubMed

    Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

    2015-10-01

    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

    PubMed

    Lindblom, Jonas; Kindlundh, Anna M S; Nyberg, Fred; Bergström, Lena; Wikberg, Jarl E S

    2003-10-03

    Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Characterization of the conformational alterations, reduced anticoagulant activity, and enhanced antiangiogenic activity of prelatent antithrombin.

    PubMed

    Richard, Benjamin; Swanson, Richard; Schedin-Weiss, Sophia; Ramirez, Ben; Izaguirre, Gonzalo; Gettins, Peter G W; Olson, Steven T

    2008-05-23

    A conformationally altered prelatent form of antithrombin that possesses both anticoagulant and antiangiogenic activities is produced during the conversion of native to latent antithrombin (Larsson, H., Akerud, P., Nordling, K., Raub-Segall, E., Claesson-Welsh, L., and Björk, I. (2001) J. Biol. Chem. 276, 11996-12002). Here, we show that the previously characterized prelatent antithrombin is a mixture of native antithrombin and a modified, true prelatent antithrombin that are resolvable by heparin-agarose chromatography. Kinetic analyses revealed that prelatent antithrombin is an intermediate in the conversion of native to latent antithrombin whose formation is favored by stabilizing anions of the Hofmeister series. Purified prelatent antithrombin had reduced anticoagulant function compared with native antithrombin, due to a reduced heparin affinity and consequent impaired ability of heparin to either bridge prelatent antithrombin and coagulation proteases in a ternary complex or to induce full conformational activation of the serpin. Significantly, prelatent antithrombin possessed an antiangiogenic activity more potent than that of latent antithrombin, based on the relative abilities of the two forms to inhibit endothelial cell growth. The prelatent form was conformationally altered from native antithrombin as judged from an attenuation of tryptophan fluorescence changes following heparin activation and a reduced thermal stability. The alterations are consistent with the limited structural changes involving strand 1C observed in a prelatent form of plasminogen activator inhibitor-1 (Dupont, D. M., Blouse, G. E., Hansen, M., Mathiasen, L., Kjelgaard, S., Jensen, J. K., Christensen, A., Gils, A., Declerck, P. J., Andreasen, P. A., and Wind, T. (2006) J. Biol. Chem. 281, 36071-36081), since the (1)H NMR spectrum, electrophoretic mobility, and proteolytic susceptibility of prelatent antithrombin most resemble those of native rather than those of latent antithrombin

  20. Do school-based physical activity interventions increase or reduce inequalities in health?

    PubMed

    Vander Ploeg, Kerry A; Maximova, Katerina; McGavock, Jonathan; Davis, Wendy; Veugelers, Paul

    2014-07-01

    Little is known about the effectiveness of school-based health promotion on physical activity inequalities among children from low-income areas. This study compared the two-year change in physical activity among 10-11 year-old children attending schools with and without health promotion programs by activity level, body weight status, and socioeconomic backgrounds to assess whether health promotion programs reduce or exacerbate health inequalities. This was a quasi-experimental trial of a Comprehensive School Health (CSH) program implemented in schools located in socioeconomically disadvantaged neighbourhoods in Edmonton, Alberta, Canada. In the spring of 2009 and 2011, pedometer (7 full days) and demographic data were collected from cross-sectional samples of grade five children from 10 intervention and 20 comparison schools. Socioeconomic status was determined from parent self-report. Low-active, active, and high-active children were defined according to step-count tertiles. Multilevel linear regression methods adjusted for potential confounders were used to assess the relative inequity in physical activity and were compared between groups and over-time. In 2009, a greater proportion of students in the intervention schools were overweight (38% vs. 31% p = 0.03) and were less active (10,827 vs. 12,265 steps/day p < 0.001). Two years later, the relative difference in step-counts between intervention and comparison schools reduced from -15.5% to 0% among low-active students, from -13.4% to 0% among active students, and from -15.1% to -2.7% among high-active students. The relative difference between intervention and comparison schools reduced from -11.1% to -1.6% among normal weight students, from -16.8% to -1.4% among overweight students, and was balanced across socioeconomic subgroups. These findings demonstrate that CSH programs implemented in socioeconomically disadvantaged neighbourhoods reduced inequalities in physical activity. Investments in school

  1. Reduced plantarflexor specific torque in the elderly is associated with a lower activation capacity.

    PubMed

    Morse, Christopher I; Thom, Jeanette M; Davis, Mark G; Fox, Ken R; Birch, Karen M; Narici, Marco V

    2004-06-01

    Previous studies have reported a decrease in muscle torque per cross-sectional area in old age. This investigation aimed at determining the influence of agonists muscle activation and antagonists co-activation on the specific torque of the plantarflexors (PF) in recreationally active elderly males (EM) and, for comparison, in young men (YM). Twenty-one EM, aged 70-82 years, and 14 YM, aged 19-35 years, performed isometric maximum voluntary contractions (MVC). Activation was assessed by comparing the amplitude of interpolated supramaximal twitch doublets at MVC, with post-tetanic doublet peak torque. Co-activation of the tibialis anterior (TA) was evaluated as the ratio of TA-integrated EMG (IEMG) activity during PF MVC compared to TA IEMG during maximal voluntary dorsiflexion. Triceps surae muscle volume (VOL) was assessed using magnetic resonance imaging (MRI), and PF peak torque was normalised to VOL (PT/VOL) since the later approximates physiological cross-sectional area (CSA) more closely than anatomical CSA. Also, physical activity level, assessed by accelerometry, was significantly lower (21%) in the elderly males. In comparison to the YM group, a greater difference in PT (39%) than VOL (19%) was found in the EM group. PT/VOL and activation capacity were respectively lower by 25% and 21% in EM compared to YM, whereas co-activation was not significantly different. In EM PT/VOL correlated with activation (R(2)=0.31, P<0.01). In conclusion, a reduction in activation capacity may contribute significantly to the decline in specific torque in the plantar flexors of elderly males. The hypothesis is put forward that reduced physical activity is partialy responsible for the reduced activation capacity in the elderly.

  2. Mouth-level intake of benzo[a]pyrene from reduced nicotine cigarettes.

    PubMed

    Ding, Yan S; Ward, Jennye; Hammond, David; Watson, Clifford H

    2014-11-18

    Cigarette smoke is a known source of exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), especially benzo[a]pyrene (BaP). Exposure to BaP in cigarette smoke is influenced by how a person smokes and factors, such as tobacco blend. To determine whether sustained use of reduced-nicotine cigarettes is associated with changes in exposure to nicotine and BaP, levels of BaP in spent cigarette filter butts were correlated with levels of BaP in cigarette smoke to estimate mouth-level intake (MLI) of BaP for 72 daily smokers given three progressively reduced nicotine content cigarettes. Urinary cotinine, a marker of nicotine exposure, and urinary 1-hydroxypyrene (1-HOP), a marker of PAH exposure, were measured throughout the study. Median daily BaP MLI and urine cotinine decreased in a similar manner as smokers switched to progressively lower nicotine cigarettes, despite relatively constant daily cigarette consumption. 1-HOP levels were less responsive to the use of reduced nicotine content cigarettes. We demonstrate that spent cigarette filter butt analysis is a promising tool to estimate MLI of harmful chemicals on a per cigarette or per-day basis, which partially addresses the concerns of the temporal influence of smoking behavior or differences in cigarette design on exposure.

  3. Mouth-Level Intake of Benzo[a]pyrene from Reduced Nicotine Cigarettes

    PubMed Central

    Ding, Yan S.; Ward, Jennye; Hammond, David; Watson, Clifford H.

    2014-01-01

    Cigarette smoke is a known source of exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), especially benzo[a]pyrene (BaP). Exposure to BaP in cigarette smoke is influenced by how a person smokes and factors, such as tobacco blend. To determine whether sustained use of reduced-nicotine cigarettes is associated with changes in exposure to nicotine and BaP, levels of BaP in spent cigarette filter butts were correlated with levels of BaP in cigarette smoke to estimate mouth-level intake (MLI) of BaP for 72 daily smokers given three progressively reduced nicotine content cigarettes. Urinary cotinine, a marker of nicotine exposure, and urinary 1-hydroxypyrene (1-HOP), a marker of PAH exposure, were measured throughout the study. Median daily BaP MLI and urine cotinine decreased in a similar manner as smokers switched to progressively lower nicotine cigarettes, despite relatively constant daily cigarette consumption. 1-HOP levels were less responsive to the use of reduced nicotine content cigarettes. We demonstrate that spent cigarette filter butt analysis is a promising tool to estimate MLI of harmful chemicals on a per cigarette or per-day basis, which partially addresses the concerns of the temporal influence of smoking behavior or differences in cigarette design on exposure. PMID:25411724

  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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Impact of reduced daily physical activity on conduit artery flow-mediated dilation and circulating endothelial microparticles

    PubMed Central

    Boyle, Leryn J.; Credeur, Daniel P.; Jenkins, Nathan T.; Padilla, Jaume; Leidy, Heather J.; Thyfault, John P.

    2013-01-01

    Physical inactivity promotes the development of cardiovascular diseases. However, few data exist examining the vascular consequences of short-term reductions in daily physical activity. Thus we tested the hypothesis that popliteal and brachial artery flow-mediated dilation (FMD) would be reduced and concentrations of endothelial microparticles (EMPs) would be elevated following reduced daily physical activity. To examine this, popliteal and brachial artery FMD and plasma levels of EMPs suggestive of apoptotic and activated endothelial cells (CD31+/CD42b− and CD62E+ EMPs, respectively) were measured at baseline and during days 1, 3, and 5 of reduced daily physical activity in 11 recreationally active men (25 ± 2 yr). Subjects were instructed to reduce daily physical activity by taking <5,000 steps/day and refraining from planned exercise. Popliteal artery FMD decreased with reduced activity (baseline: 4.7 ± 0.98%, reduced activity day 5: 1.72 ± 0.68%, P < 0.05), whereas brachial artery FMD was unchanged. In contrast, baseline (pre-FMD) popliteal artery diameter did not change, whereas brachial artery diameter decreased (baseline: 4.35 ± 0.12, reduced activity day 5: 4.12 ± 0.11 P < 0.05) following 5 days of reduced daily physical activity. CD31+/CD42b− EMPs were significantly elevated with reduced activity (baseline: 17.6 ± 9.4, reduced activity day 5: 104.1 ± 43.1 per μl plasma, P < 0.05), whereas CD62E+ EMPs were unaltered. Collectively, our results provide evidence for the early and robust deleterious impact of reduced daily activity on vascular function and highlight the vulnerability of the vasculature to a sedentary lifestyle. PMID:24072406

  6. Downregulation of Parvalbumin at Cortical GABA Synapses Reduces Network Gamma Oscillatory Activity

    PubMed Central

    Volman, Vladislav; Behrens, M. Margarita; Sejnowski, Terrence J.

    2012-01-01

    Postmortem and functional imaging studies of patients with psychiatric disorders, including schizophrenia, are consistent with a dysfunction of interneurons leading to compromised inhibitory control of network activity. Parvalbumin (PV)-expressing, fast-spiking interneurons interacting with pyramidal neurons generate cortical gamma oscillations (30 – 80 Hz) that synchronize cortical activity during cognitive processing. In postmortem studies of schizophrenia patients, these interneurons show reduced PV and glutamic acid decarboxylase 67 (GAD67), an enzyme that synthesizes GABA, but the consequences of this downregulation are unclear. We developed a biophysically realistic and detailed computational model of a cortical circuit including asynchronous release from GABAergic interneurons to investigate how reductions in PV and GABA affect gamma oscillations induced by sensory stimuli. Networks with reduced GABA were disinhibited and had altered gamma oscillations in response to stimulation; PV-deficient GABA synapses had increased asynchronous release of GABA, which decreased the level of excitation and reduced gamma-band activity. Combined reductions of PV and GABA resulted in a diminished gamma-band oscillatory activity in response to stimuli, similar to that observed in schizophrenia patients. Our results suggest a mechanism by which reduced GAD67 and PV in fast-spiking interneurons may contribute to cortical dysfunction in schizophrenia and related psychiatric disorders. PMID:22159125

  7. Reduced rat plasma lysophosphatidylglycerol or lysophosphatidic acid level as a biomarker of aristolochic acid-induced renal and adipose dysfunctions.

    PubMed

    Tsutsumi, Toshihiko; Okamoto, Yoko; Yamakawa, Syougo; Bingjun, Cheng; Ishihara, Akira; Tanaka, Tamotsu; Tokumura, Akira

    2016-07-15

    Food products and diet pills containing aristolochic acid (AA) are responsible for a rapid progression of nephropathy associated with reduced body weight in human beings. In this study, we investigated the relationship of dietary NaCl and lysophospholipid (LPL) plasma levels to body weight gain in AA-treated rats. Male rats receiving a salt-deficient chow, normal salt chow or high salt chow were injected intraperitoneally daily with AA for 15days. Body weight, visceral fat mass, food intake, levels of LPL in plasma and its synthesized enzyme were investigated. Body weight gain, visceral fat mass and daily food intake were smaller in AA-treated rats than those of control rats, regardless of dietary salt concentration. AA treatment decreased plasma levels of major lysophosphatidic acid (LPA) molecular species in rats fed the normal or high-salt chow but not the salt-deficient chow, whereas both the plasma lysophospholipase D activity and kidney mRNA level of autotaxin of AA-treated rats fed chow with defined salt concentrations were lower than those of control rats. Plasma levels of major molecular species of lysophosphatidylglycerol (LPG) in AA-treated rat groups fed chow with defined salt concentrations were lower than those of control rats. Plasma levels of LPG and LPA seem to be relevant to the reduced body weight gain and fat mass due to AA treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  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

    2013-05-27

    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.

  9. Inhibition of Hyaluronan Synthesis Reduces Versican and Fibronectin Levels in Trabecular Meshwork Cells

    PubMed Central

    Keller, Kate E.; Sun, Ying Ying; Vranka, Janice A.; Hayashi, Lauren; Acott, Ted S.

    2012-01-01

    Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and is synthesized by three HA synthases (HAS). Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU), or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process. PMID:23139787

  10. Transgenic tobacco plants overexpressing glyoxalase enzymes resist an increase in methylglyoxal and maintain higher reduced glutathione levels under salinity stress.

    PubMed

    Yadav, Sudesh Kumar; Singla-Pareek, Sneh L; Reddy, M K; Sopory, S K

    2005-11-07

    The mechanism behind enhanced salt tolerance conferred by the overexpression of glyoxalase pathway enzymes was studied in transgenic vis-à-vis wild-type (WT) plants. We have recently documented that salinity stress induces higher level accumulation of methylglyoxal (MG), a potent cytotoxin and primary substrate for glyoxalase pathway, in various plant species [Yadav, S.K., Singla-Pareek, S.L., Ray, M., Reddy, M.K. and Sopory, S.K. (2005) MG levels in plants under salinity stress are dependent on glyoxalase I and glutathione. Biochem. Biophys. Res. Commun. 337, 61-67]. The transgenic tobacco plants overexpressing glyoxalase pathway enzymes, resist an increase in the level of MG that increased to over 70% in WT plants under salinity stress. These plants showed enhanced basal activity of various glutathione related antioxidative enzymes that increased further upon salinity stress. These plants suffered minimal salinity stress induced oxidative damage measured in terms of the lipid peroxidation. The reduced glutathione (GSH) content was high in these transgenic plants and also maintained a higher reduced to oxidized glutathione (GSH:GSSG) ratio under salinity. Manipulation of glutathione ratio by exogenous application of GSSG retarded the growth of non-transgenic plants whereas transgenic plants sustained their growth. These results suggest that resisting an increase in MG together with maintaining higher reduced glutathione levels can be efficiently achieved by the overexpression of glyoxalase pathway enzymes towards developing salinity stress tolerant plants.

  11. Plasma Levels of Soluble Interleukin 1 Receptor Accessory Protein Are Reduced in Obesity

    PubMed Central

    Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P.; Carless, Melanie A.; Shields, Katherine A.; Johnson, Matthew P.; Kowlessur, Sudhir; Dyer, Thomas D.; Comuzzie, Anthony G.; Almasy, Laura; Zimmet, Paul; Moses, Eric K.; Göring, Harald H. H.; Curran, Joanne E.; Blangero, John; Jowett, Jeremy B. M.

    2014-01-01

    Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. Objective: The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. Results: A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10−23) within the IL1RAP gene. Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity. PMID:24915116

  12. Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity.

    PubMed

    Bozaoglu, Kiymet; Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P; Carless, Melanie A; Shields, Katherine A; Johnson, Matthew P; Kowlessur, Sudhir; Dyer, Thomas D; Comuzzie, Anthony G; Almasy, Laura; Zimmet, Paul; Moses, Eric K; Göring, Harald H H; Curran, Joanne E; Blangero, John; Jowett, Jeremy B M

    2014-09-01

    Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10(-23)) within the IL1RAP gene. Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

  13. Physical activity levels of children during school playtime.

    PubMed

    Ridgers, Nicola D; Stratton, Gareth; Fairclough, Stuart J

    2006-01-01

    School represents a suitable setting for intervention programmes aiming to promote physical activity to benefit health. During the school day, physical education and school playtime offer children regular opportunities to engage in physical activity. However, there is growing concern that, internationally, curricular time allocated to physical education is not meeting statutory guidelines. The effectiveness of the playground environment to promote physical activity has been considered as a complementary setting to physical education. Physical activity guidelines state that children should engage in at least 1 hour of moderate intensity physical activity a day. Currently no empirically tested guidelines exist for physical activity levels during playtime. However, studies cited in this article indicate that playtime can contribute between 5-40% of recommended daily physical activity levels when no interventions have been utilised. The limited school-based investigations that have been reported in the literature suggest that boys engage in more physical activity during playtime than girls. Studies that have implemented intervention strategies in order to promote physical activity levels indicate that playtime can substantially contribute towards daily optimal physical activity guidelines. Energy expenditure and physical activity levels have increased during playtime following the implementation of playtime-based interventions. In order to advance knowledge of children's physical activity during playtime, a number of key issues for consideration in future research are detailed. Research on children's use of playtime to be physically active and the extent of the contribution of playtime to daily physical activity guidelines is warranted.

  14. Live music reduces stress levels in very low-birthweight infants.

    PubMed

    Schwilling, Diana; Vogeser, Michael; Kirchhoff, Fabian; Schwaiblmair, Frauke; Boulesteix, Anne-Laure; Schulze, Andreas; Flemmer, Andreas W

    2015-04-01

    Music might benefit preterm infants in stressful, intensive care environments. However, data on stress level indicators, determined by salivary cortisol levels, are scarce. We evaluated the effect of live harp music on the stress level indicators of preterm infants in a neonatal intensive care unit (NICU). We exposed 20 stable preterm infants to music for 15 min on three consecutive days. Saliva was collected before the music was played and 25 min and 4 h after it ended. Salivary cortisol levels were measured by liquid chromatography-tandem mass spectrometry and vital signs, oxygen saturation, bradycardia, apnoeas and oxygen desaturations were recorded. Pain levels were assessed by the Bernese Pain Scale for Neonates. Salivary cortisol was significantly lower 25 min (18.9 nmol/L [3.9-35.6] p = 0.001) and 4 h after music (17.4 nmol/L [3.9-35.3] p = 0.003) than at baseline 4 h before exposure (19.5 nmol/L [7.2-51.1]). After music, the number of apnoeas and oxygen desaturations was significantly reduced on all three, days and the number of bradycardia episodes on day one. Pain scores significantly improved after music on all 3 days. Exposure to live music reduced salivary cortisol and had beneficial effects on the physiologic parameters of stable preterm infants in a NICU. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  15. 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.

  16. Modulation of GDP-fucose level for generating proteins with reduced rate of fucosylation (WO2010141855).

    PubMed

    Taupin, Philippe

    2011-09-01

    The application (WO2010141855) is in the field of glycobiology, and involves the control of the rate of fucosylation of proteins by exogenous factors. It aims at controlling the rate of protein fucosylation with inhibitors (drugs or nucleic acid antagonists) of enzymes involved in the synthesis of GDP-fucose. Mammalian cell lines were cultured in the presence of inhibitors, for example, siRNA. The rates of GDP-fucose in cells and during protein fucosylation were characterized. The level of protein fucosylation decreases rapidly in response to a decrease in GDP-fucose level. The relationship between the rate of fucosylation of proteins and the level of GDP-fucose in a cell is non-linear. Reduction in the rate of protein fucosylation can be achieved with a minimal reduction of the level of GDP-fucose in cells. The paradigm may be used to synthesize proteins and antibodies, with a reduced rate of fucosylation. The application claims that the use of drugs or nucleic acid antagonists that inhibit the enzymes involved in GDP-fucose biosynthesis optimizes the level of GDP-fucose present in cells, and reduces the rate of fucosylation of glycoproteins.

  17. 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

    2016-01-01

    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.

  18. Induction of early meconium evacuation: is it effective in reducing the level of neonatal hyperbilirubinemia?

    PubMed

    Bader, David; Yanir, Yoav; Kugelman, Amir; Wilhelm-Kafil, Mira; Riskin, Arieh

    2005-08-01

    This prospective randomized trial evaluated the effect of induction of early meconium evacuation on neonatal jaundice in healthy term neonates. The study group was given glycerin suppository immediately after birth and every 4 hours thereafter, until evacuation of first stool. Glycerin suppository caused faster meconium evacuation but had no effect on mean bilirubin levels at 48 hours. However, males had significantly lower mean bilirubin levels, especially if they also had type A blood group. Glycerin suppository cannot be routinely recommended as a means for reducing the severity of neonatal jaundice. Nonetheless, male newborn with type A blood group may benefit from such a therapy.

  19. Reducing FLI1 Levels in the MRL/lpr Lupus Mouse Model Impacts T Cell Function by Modulating Glycosphingolipid Metabolism

    PubMed Central

    Richard, Erin Morris; Thiyagarajan, Thirumagal; Bunni, Marlene A.; Basher, Fahmin; Roddy, Patrick O.; Siskind, Leah J.; Nietert, Paul J.; Nowling, Tamara K.

    2013-01-01

    Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1+/+ or Fli1+/- T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1+/- lupus T cells compared to animals receiving Fli1+/+ lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1+/- T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1+/+ T cells. Moreover, the Fli1+/- T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1+/+ T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus. PMID:24040398

  20. 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

  1. Suppressing emotions impairs subsequent stroop performance and reduces prefrontal brain activation.

    PubMed

    Friese, Malte; Binder, Julia; 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.

  2. 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

  3. 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).

  4. 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.

  5. 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

  6. 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

    2016-06-06

    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.

  7. 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

  8. 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.

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

    PubMed

    Basavarajappa, Mallikarjuna S; Craig, Zelieann R; Hernández-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 (E₂) 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 E₂ metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E₂, testosterone, androstenedione, and progesterone (P₄) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β 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.

  10. 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.

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

    PubMed

    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.

  12. 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

  13. 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.

  14. AMPK up-activation reduces motility and regulates other functions of boar spermatozoa.

    PubMed

    Hurtado de Llera, A; Martin-Hidalgo, D; Gil, M C; Garcia-Marin, L J; Bragado, M J

    2015-01-01

    We recently demonstrated that AMPK inhibition in spermatozoa regulates motility, plasma membrane organization, acrosome integrity and mitochondrial membrane potential. As AMPK activity varies in different energy conditions induced by sperm environment, this work investigates the functional effects of AMPK activation in boar spermatozoa. Spermatozoa were incubated under non-stimulating (TBM) or Ca(2+) and [Formula: see text]-stimulating (TCM) media in the presence/absence of AMPK activator, A769662, for different times. AMPK activity, evaluated as Thr(172) phosphorylation by western blot, is effectively increased by A769662 in spermatozoa. AMPK activation significantly reduces the percentage of motile spermatozoa under Ca(2+) and/or [Formula: see text]-stimulating conditions. Moreover, AMPK activation in spermatozoa incubated in TBM or TCM significantly reduces curvilinear VCL, straight-line VSL and average VAP velocities, which subsequently lead to a significant decrease in the percentage of rapid spermatozoa (VAP > 80 μm/s). The effect of AMPK activation on motility is intensified by the absence of BSA in the incubation medium. AMPK activation for a short time prevents the decline in cell viability and in the sperm population displaying high mitochondrial membrane potential which is induced by Ca(2+) and [Formula: see text]. Sustained (24 h) AMPK activation under TBM or TCM significantly increases both lipid disorganization and phosphatidylserine externalization in the sperm plasma membrane, and diminishes the acrosome membrane integrity. In summary, AMPK activation modifies essential sperm processes such as motility, viability, mitochondrial membrane potential, acrosome membrane integrity, and organization and fluidity of plasma membrane. As these spermatozoa processes are required under different environmental conditions when transiting through the female reproductive tract to achieve fertilization, we conclude that balanced levels of AMPK activity are

  15. 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

  16. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Stante, A; Dello Russo, P; Torella, R

    1989-01-01

    Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

  18. Reduced Activity of Antioxidant Machinery Is Correlated with Suppression of Totipotency in Plant Protoplasts1

    PubMed Central

    Papadakis, Anastasia K.; Siminis, Charalambos I.; Roubelakis-Angelakis, Kalliopi A.

    2001-01-01

    We previously showed that during protoplast isolation, an oxidative burst occurred and the generation of active oxygen species was differentially mediated in tobacco (Nicotiana tabacum) and grapevine (Vitis vinifera), accompanied by significant quantitative differences (A.K. Papadakis, K.A. Roubelakis-Angelakis [1999] Plant Physiol 127: 197–205). We have now further tested if the expression of totipotency in protoplasts is related to the activity of cellular antioxidant machinery during protoplast culture. Totipotent (T) tobacco protoplasts had 2-fold lower contents of intracellular O2.− and H2O2 and 7-fold lower levels of O2.− and H2O2 in the culture medium, compared with non-totipotent (NT) tobacco protoplasts. Addition of alkaline dimethylsulfoxide, known to generate O2.−, resulted in isolation of tobacco protoplasts with reduced viability and cell division potential during subsequent culture. Active oxygen species levels decreased in tobacco and grapevine protoplasts during culturing, although higher contents of O2.− and H2O2 were still found in NT- compared with T-tobacco protoplasts, after 8 d in culture. In T-tobacco protoplasts, the reduced forms of ascorbate and glutathione predominated, whereas in NT-tobacco and grapevine protoplasts, the oxidized forms predominated. In addition, T-tobacco protoplasts exhibited severalfold lower lipid peroxidation than NT-tobacco and grapevine protoplasts. Furthermore, several antioxidant enzyme activities were increased in T-tobacco protoplasts. Superoxide dismutase activity increased in tobacco, but not in grapevine protoplasts during culturing due to the increased expression of cytoplasmic Cu/Zn-superoxide dismutase. The increase was only sustained in T-tobacco protoplasts for d 8. Together, these results suggest that suppressed expression of totipotency in protoplasts is correlated with reduced activity of the cellular antioxidant machinery. PMID:11351105

  19. Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription

    PubMed Central

    Huang, Haiyan; Joseph, Leroy C.; Gurin, Michael I.; Thorp, Edward B.; Morrow, John P.

    2014-01-01

    Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that Extracellular Signal-regulated Kinase (ERK) 1/2 activation during hypertrophy reduced SERCA2 transcription. Using a neonatal rat ventricular myocyte model of hypertrophy, we found that pharmacologic inhibitors of ERK activation preserve SERCA2 mRNA levels during hypertrophy. ERK activation is sufficient to reduce SERCA2 mRNA. We determined that ERK represses SERCA2 transcription via nuclear factor-kappaB (NFkB), and activation of NFkB is sufficient to reduce SERCA2 mRNA in cardiomyocytes. This work establishes novel connections between ERK, NFkB, and SERCA2 repression during cardiac hypertrophy. This mechanism may have implications for the progression of hypertrophy to heart failure. PMID:25008120

  20. 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

  1. Relationship between activity levels and circadian blood pressure variations.

    PubMed

    Kohno, I; Ishii, H; Nakamura, T; Tamura, K

    1993-01-01

    In 17 healthy Japanese students (14 males and 3 females) an ambulatory activity level monitoring instrument (Actigraph) was attached to the wrist for 48-hour measurement of wrist movement (with 0.01G or higher acceleration). At the same time, an ambulatory blood pressure monitoring apparatus was attached to these subjects to monitor blood pressure (BP) and heart rate (HR) every 30 minutes. Sleeping hours were calculated from the activity levels. The sleeping hours obtained by the Actigraph correlated with those judged from the diary. The correlation was better for the go-to-sleep time than for the awakening time. Activity level, HR and BP showed a similar circadian variation. Activity level differed significantly between the active daytime (4500 counts/hour) and during sleep at night (720 counts/hour). The acrophase of activity level, obtained by the cosinor method, was 235 degrees which did not significantly differ from that of BP and HR. Hourly activity levels correlated with HR and BP at corresponding hours. These results suggest that BP is affected by activity levels even if this rhythm continues to recur in bedrest.

  2. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity

    PubMed Central

    Heinrich, Garrett; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; DeAngelis, Anthony M.; Bowman, Thomas A.; Ghadieh, Hilda E.; Ghanem, Simona S.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species. PMID:28396653

  3. Apathy and APOE4 are associated with reduced BDNF levels in Alzheimer's disease.

    PubMed

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

    2014-01-01

    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 ε4 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.

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

    PubMed

    Taft, Angela; Small, Rhonda

    2014-10-01

    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.

  5. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity.

    PubMed

    Heinrich, Garrett; Muturi, Harrison T; Rezaei, Khadijeh; Al-Share, Qusai Y; DeAngelis, Anthony M; Bowman, Thomas A; Ghadieh, Hilda E; Ghanem, Simona S; Zhang, Deqiang; Garofalo, Robert S; Yin, Lei; Najjar, Sonia M

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.

  6. Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury.

    PubMed

    McKillop, William M; Dragan, Magdalena; Schedl, Andreas; Brown, Arthur

    2013-02-01

    Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock-out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic level 9. One week after injury, Sox9 conditional knock-out mice expressed reduced levels of CSPG biosynthetic enzymes (Xt-1 and C4st), CSPG core proteins (brevican, neurocan, and aggrecan), collagens 2a1 and 4a1, and Gfap, a marker of astrocyte activation, in the injured spinal cord compared with controls. These changes in gene expression were accompanied by improved hind limb function and locomotor recovery as evaluated by the Basso Mouse Scale (BMS) and rodent activity boxes. Histological assessments confirmed reduced CSPG deposition and collagenous scarring at the lesion of Sox9 conditional knock-out mice, and demonstrated increased neurofilament-positive fibers in the lesion penumbra and increased serotonin immunoreactivity caudal to the site of injury. These results suggest that SOX9 inhibition is a potential strategy for the treatment of SCI.

  7. Dual-Level LVDS Technique for Reducing Data Transmission Lines by Half in LCD Driver IC's

    NASA Astrophysics Data System (ADS)

    Kim, Doo-Hwan; Yang, Sung-Hyun; Cho, Kyoung-Rok

    This paper proposes a dual-level low voltage differential signaling (DLVDS) circuit aimed at low power consumption and reducing transmission lines for LCD driver IC's. We apply two-bit binary data to the DLVDS circuit as inputs, and then the circuit converts these two inputs into two kinds of fully differential signal levels. In the DLVDS circuit, two transmission lines are sufficient to transfer two-bit binary inputs while keeping the conventional LVDS features. The receiver recovers the original two-bit binary data through a level decoding circuit. The proposed circuit was fabricated using a commercial 0.25μm CMOS technology. Under a 2.5V supply voltage, the circuit shows a data rate of 1-Gbps/2-line and power consumption of 35mW.

  8. 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…

  9. Demonstrating Reduced Environmental and Genetic Diversity in Human Isolates by Analysis of Blood Lipid Levels

    PubMed Central

    Polašek, Ozren; Kolčić, Ivana; Smoljanović, Ankica; Stojanović, Dražen; Grgić, Matijana; Ebling, Barbara; Klarić, Maja; Milas, Josip; Puntarić, Dinko

    2006-01-01

    Aim To test the hypothesis that phenotypic diversity in isolated human populations is decreased in comparison with general outbred population because of reduced genetic and environmental diversity. To demonstrate this in populations for which reduced genetic and environmental diversity had already been established, by studying the amount of variation in plasma lipid levels. Methods Fasting plasma lipid levels (cholesterol, triglycerides, low density lipoprotein [LDL], and high density lipoprotein [HDL]) were measured in randomly selected 300 inhabitants from 2 isolated human populations, the island of Rab and the neighboring islands of Vis and Lastovo, Croatia. The populations were chosen based on previous analyses of genetic diversity and lifestyle patterns, which were shown to be both less diverse and more uniform than the general Croatian population. We studied whether the 25’-75’ and 5′-95’ interpercentile ranges in observed values were consistently smaller in 2 samples of 300 examinees from isolated populations in comparison with nearly 6000 examinees from an earlier study who were demographically targeted to represent the larger Croatian population. Results General population had much wider range of observed values of triglycerides and HDL than both isolated populations. However, both isolated populations exhibited greater extent of variation in the levels of LDL, while the ranges of cholesterol values were similar. Conclusion Although reduced genetic and environmental diversity in isolated human populations should necessarily reduce the variance in observed phenotypic values, it appears that specific population genetic processes in isolated populations could be acting to maintain the variation. Departure from the Hardy-Weinberg equilibrium due to consanguinity, sub-structuring and differentiation within the isolates, and increased rate of new mutations could theoretically explain this paradox. PMID:16909463

  10. Reducing Jagged 1 and 2 levels prevents cerebral arteriovenous malformations in matrix Gla protein deficiency.

    PubMed

    Yao, Yucheng; Yao, Jiayi; Radparvar, Melina; Blazquez-Medela, Ana M; Guihard, Pierre J; Jumabay, Medet; Boström, Kristina I

    2013-11-19

    Cerebral arteriovenous malformations (AVMs) are common vascular malformations, which may result in hemorrhagic strokes and neurological deficits. Bone morphogenetic protein (BMP) and Notch signaling are both involved in the development of cerebral AVMs, but the cross-talk between the two signaling pathways is poorly understood. Here, we show that deficiency of matrix Gla protein (MGP), a BMP inhibitor, causes induction of Notch ligands, dysregulation of endothelial differentiation, and the development of cerebral AVMs in MGP null (Mgp(-/-)) mice. Increased BMP activity due to the lack of MGP induces expression of the activin receptor-like kinase 1, a BMP type I receptor, in cerebrovascular endothelium. Subsequent activation of activin receptor-like kinase 1 enhances expression of Notch ligands Jagged 1 and 2, which increases Notch activity and alters the expression of Ephrin B2 and Ephrin receptor B4, arterial and venous endothelial markers, respectively. Reducing the expression of Jagged 1 and 2 in the Mgp(-/-) mice by crossing them with Jagged 1 or 2 deficient mice reduces Notch activity, normalizes endothelial differentiation, and prevents cerebral AVMs, but not pulmonary or renal AVMs. Our results suggest that Notch signaling mediates and can modulate changes in BMP signaling that lead to cerebral AVMs.

  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. Active Coping Reduces Reports of Pain from Childbirth.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    1989-01-01

    Examined pain and negative moods during labor in relation to instructions to monitor labor contractions and LaMaze class attendance. In Study 1, pain and negative moods showed sharp decline at Stage 2 (active labor) for women who monitored and LaMaze participants; in Study 2, LaMaze participants reported decline in pain during active labor and…

  13. 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…

  14. 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.

  15. Two-Level Incremental Checkpoint Recovery Scheme for Reducing System Total Overheads

    PubMed Central

    Li, Huixian; Pang, Liaojun; Wang, Zhangquan

    2014-01-01

    Long-running applications are often subject to failures. Once failures occur, it will lead to unacceptable system overheads. The checkpoint technology is used to reduce the losses in the event of a failure. For the two-level checkpoint recovery scheme used in the long-running tasks, it is unavoidable for the system to periodically transfer huge memory context to a remote stable storage. Therefore, the overheads of setting checkpoints and the re-computing time become a critical issue which directly impacts the system total overheads. Motivated by these concerns, this paper presents a new model by introducing i-checkpoints into the existing two-level checkpoint recovery scheme to deal with the more probable failures with the smaller cost and the faster speed. The proposed scheme is independent of the specific failure distribution type and can be applied to different failure distribution types. We respectively make analyses between the two-level incremental and two-level checkpoint recovery schemes with the Weibull distribution and exponential distribution, both of which fit with the actual failure distribution best. The comparison results show that the total overheads of setting checkpoints, the total re-computing time and the system total overheads in the two-level incremental checkpoint recovery scheme are all significantly smaller than those in the two-level checkpoint recovery scheme. At last, limitations of our study are discussed, and at the same time, open questions and possible future work are given. PMID:25111048

  16. 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.

  17. Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease.

    PubMed

    Marzocco, Stefania; Dal Piaz, Fabrizio; Di Micco, Lucia; Torraca, Serena; Sirico, Maria Luisa; Tartaglia, Domenico; Autore, Giuseppina; Di Iorio, Biagio

    2013-01-01

    High levels of indoxyl sulfate (IS) are associated with chronic kidney disease (CKD) progression and increased mortality in CKD patients. The aim of this pilot study was to assess whether a very low protein diet (VLPD; 0.3 g/kg bw/day), with a consequent low phosphorus intake, would reduce IS serum levels compared to a low protein diet (LPD; 0.6 g/kg bw/day) in CKD patients not yet on dialysis. This is a post hoc analysis of a preceding cross-over study aimed to analyze FGF23 during VLPD. Here we performed a prospective randomized controlled crossover study in which 32 patients were randomized to receive either a VLPD (0.3 g/kg bw/day) supplemented with ketoanalogues during the first week and an LPD during the second week (group A, n = 16), or an LPD during the first week and a VLPD during the second week (group B, n = 16 patients). IS serum levels were measured at baseline and at the end of each study period. We compared them to 24 hemodialysis patients (HD) and 14 healthy subjects (control). IS serum concentration was significantly higher in the HD (43.4 ± 12.3 µM) and CKD (11.1 ± 6.6 µM) groups compared to the control group (2.9 ± 1.1 µM; p < 0.001). IS levels also correlated with creatinine values in CKD patients (R(2) = 0.42; p < 0.0001). After only 1 week of a VLPD, even preceded by an LPD, CKD patients showed a significant reduction of IS serum levels (37%). VLPD supplemented with ketoanalogues reduced IS serum levels in CKD patients not yet on dialysis. Copyright © 2013 S. Karger AG, Basel.

  18. Reduced Levels of Nitric Oxide Metabolites in Cerebrospinal Fluid Are Associated with Equine Protozoal Myeloencephalitis

    PubMed Central

    Njoku, Chinedu J.; Saville, William J. A.; Reed, Stephen M.; Oglesbee, Michael J.; Rajala-Schultz, Päivi J.; Stich, Roger W.

    2002-01-01

    Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NOx−) in the cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NOx− levels were measured before and after transport-stressed, acclimated, or dexamethasone-treated horses (n = 3 per group) were experimentally infected with S. neurona sporocysts. CSF NOx− levels were also compared between horses that were diagnosed with EPM after natural infection with S. neurona and horses that did not have clinical signs of disease or that showed no evidence of infection with the parasite (n = 105). Among the experimentally infected animals, the mean CSF NOx− levels of the transport-stressed group, which had the most severe clinical signs, was reduced after infection, while these values were found to increase after infection in the remaining groups that had less severe signs of EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF NOx− concentration than clinically normal horses with antibodies (Abs) against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had a significantly lower mean CSF NOx− concentration than horses that did not have neurologic signs (n = 24). In conclusion, lower CSF NOx− levels were associated with clinical EPM, suggesting that measurement of CSF NOx− levels could improve the accuracy of diagnostic tests that are based upon detection of S. neurona-specific Abs in CSF alone and that reduced NO levels could be causatively related to the development

  19. Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake.

    PubMed

    Fowke, Jay H; Morrow, Jason D; Motley, Saundra; Bostick, Roberd M; Ness, Reid M

    2006-10-01

    Isothiocyanates and indoles (e.g. indole-3-carbinol) from Brassica vegetables (e.g. broccoli) induce Phase I and Phase II enzymes responsible for the oxidation, reduction and metabolism of endogenous and exogenous carcinogens. Brassica vegetables also contain micronutrients that may provide additional DNA protection from reactive oxygen species. This randomized crossover trial (n = 20) compares the effects of a Brassica Vegetable (BV) intervention against a Micronutrient and Fiber Supplementation (M+F) intervention on urinary F2-isoprostane levels (F2-iP), a stable biomarker of systemic oxidative stress. Brassica intake was monitored by repeated 24 h recalls, urinary ITC levels and questionnaire. Urinary F2-iP levels were measured by mass spectrometry from first-morning urine samples collected at Baseline and after each intervention, and change in natural log transformed urinary F2-iP levels were analyzed using repeated measures regression. Brassica consumption increased from 2 grams/day (g/d) during the Baseline or M+F intervention periods to 218 g/d during the BV intervention, whereas exposure to most antioxidant vitamins and minerals was greatest during the M+F intervention. F2-iP levels significantly decreased by 22.0 or 21.8% during the BV intervention compared with Baseline or the M+F intervention (P = 0.05, P = 0.05, respectively). Urinary F2-iP levels did not significantly differ between Baseline and the M+F intervention (difference = 0.2%; P = 0.98). Brassica intake has been associated with reduced risk of colon, lung, bladder, breast, prostate and other cancers. Our results suggest that Brassica consumption reduces systemic oxidative stress independent of the vitamin and mineral content of these vegetables.

  20. Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells.

    PubMed

    Hock, Barry D; MacPherson, Sean A; McKenzie, Judith L

    2017-01-01

    Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways. Caffeine is both an adenosine receptor antagonist and a phosphatidylinositol-3-kinase, p110δ (PI3Kδ) inhibitor and, at physiologically relevant levels, significantly reversed suppression. Significant reversal of suppression was also observed with the PI3Kδ specific inhibitor Idelalisib but not with adenosine receptor specific antagonists. Furthermore, addition of caffeine or Idelalisib to activated CLL cells significantly inhibited phosphorylation of AKT, a downstream kinase of PI3K, but did not affect CLL viability. These results suggest that caffeine, in common with Idelalisib, reduces the immuno-suppressive activity of activated CLL cells by inhibiting PI3Kδ. These findings raise the possibility that these compounds may provide a useful therapeutic adjunct by reducing immuno-suppression within the tumor micro-environment of CLL.

  1. Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells

    PubMed Central

    Hock, Barry D.; MacPherson, Sean A.; McKenzie, Judith L.

    2017-01-01

    Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways. Caffeine is both an adenosine receptor antagonist and a phosphatidylinositol-3-kinase, p110δ (PI3Kδ) inhibitor and, at physiologically relevant levels, significantly reversed suppression. Significant reversal of suppression was also observed with the PI3Kδ specific inhibitor Idelalisib but not with adenosine receptor specific antagonists. Furthermore, addition of caffeine or Idelalisib to activated CLL cells significantly inhibited phosphorylation of AKT, a downstream kinase of PI3K, but did not affect CLL viability. These results suggest that caffeine, in common with Idelalisib, reduces the immuno-suppressive activity of activated CLL cells by inhibiting PI3Kδ. These findings raise the possibility that these compounds may provide a useful therapeutic adjunct by reducing immuno-suppression within the tumor micro-environment of CLL. PMID:28257435

  2. Activation of the Acquired Immune Response Reduces Coupled Bone Formation in Response to a Periodontal Pathogen

    PubMed Central

    Behl, Yugal; Siquiera, Michelle; Ortiz, Javier; Desta, Tesfahun; Faibish, Dan; Graves, Dana T.

    2009-01-01

    Osteoimmunology involves the interaction of the immune system with skeletal elements. This interaction can lead to the formation of osseous lesions. To investigate how the acquired immune response could contribute to osteolytic lesions we injected the periodontal pathogen Porphyromonas gingivalis adjacent to calvarial bone with or without prior immunization against the bacterium. Activation of the acquired immune response increased osteoclastogenesis and decreased coupled bone formation. The latter was accompanied by an increase in nuclear translocation of the transcription factor FOXO1 in vivo, increased apoptosis of bone-lining cells and a decrease in bone lining cell density. Further studies were carried out with MC3T3 osteoblastic cells. Apoptosis and increased FOXO1 DNA binding activity were induced when a combination of cytokines was tested, IL-β, TNF-α, and IFN-γ. Knockdown of FOXO1 by siRNA significantly reduced cytokine stimulated apoptosis, cleaved caspase-3/7 activity and decreased mRNA levels of the proapoptotic genes, TNF-α, FADD, caspase-3, -8 and -9. These results indicate that activation of the acquired immunity by a periodontal pathogen reduces the coupling of bone formation and resorption. This may occur by enhancing bone lining cell apoptosis through a mechanism that involves increased FOXO1 activation. These studies give insight into inflammatory bone diseases such as periodontal disease and arthritis were the formation of lytic lesions occurs in conjunction with deficient bone formation and activation of an acquired immune response. PMID:19050291

  3. Antiretroviral treatment effect on immune activation reduces cerebrospinal fluid HIV-1 infection.

    PubMed

    Sinclair, Elizabeth; Ronquillo, Rollie; Lollo, Nicole; Deeks, Steven G; Hunt, Peter; Yiannoutsos, Constantin T; Spudich, Serena; Price, Richard W

    2008-04-15

    To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations. Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1-infected subjects divided into 3 groups: not on ART (termed "offs"), on ART with plasma HIV-1 RNA >500 copies/mL ("failures"), and on ART with plasma HIV-1 RNA activation was measured by coexpression of CD38 and human leukocyte antigen DR (HLA-DR). Other measurements included CSF neopterin and white blood cell (WBC) counts. CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels. The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels.

  4. Do productive activities reduce inflammation in later life? Multiple roles, frequency of activities, and C-reactive protein.

    PubMed

    Kim, Seoyoun; Ferraro, Kenneth F

    2014-10-01

    The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. The study uses a representative survey of adults aged 57-85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Productive activities-and frequent volunteering in particular-may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. 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.

  6. Barley sprout extracts reduce hepatic lipid accumulation in ethanol-fed mice by activating hepatic AMP-activated protein kinase.

    PubMed

    Kim, Yeon-Ji; Hwang, Su Hyeon; Jia, Yaoyao; Seo, Woo-Duck; Lee, Sung-Joon

    2017-11-01

    Chronic alcohol consumption leads to hepatic lipid accumulation and alcoholic fatty liver disease. Previously, we demonstrated that barley sprout extract, which contains saponarin as an active compound, reduces hepatic steatosis. In this study, we investigated the effect of barley sprout extracts (BSE) on hepatic lipid accumulation in a mouse model of alcoholic fatty liver disease. Seven-week-old C57BL/6 mice were fed an alcohol-containing diet (5% ethanol) and a low or high dose of BSE (100 or 200mg/kg body weight, respectively) for 10days. The high dose of BSE significantly decreased hepatic lipid accumulation compared with the ethanol-only control group. In the second animal study, mice were fed an alcohol-containing diet for 10days, followed by a 45% high-fat diet with oral administration of BSE (100 or 200mg/day/kg body weight) for 4weeks. Mice in both BSE-fed groups showed reduced hepatic steatosis. In the livers of mice fed BSE, phosphorylation of AMP-activated protein kinase (AMPK) was increased, and expression of hepatic autophagy markers was elevated. In cultured hepatocytes, BSE (200μg/mL) increased the rate of fatty acid oxidation and reduced that of fatty acid synthesis. Taken together, these findings suggest that BSE promotes degradation of lipid droplets and subsequent activation of fat oxidation by activating AMPK in the liver, thus protecting against development of hepatic steatosis in alcohol-fed mice. Saponarin, a major flavonoid in BSE and an activator of AMPK, increased the activity of microsomal triglyceride transfer protein, which suggests that the reduction in hepatic triglyceride levels was mediated by this component of BSE. In conclusion, BSE ameliorated hepatic steatosis in a mouse model of ethanol-induced fatty liver by activating AMPK, an effect possibly mediated by the saponarin component. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Phytochelatin synthase OsPCS1 plays a crucial role in reducing arsenic levels in rice grains.

    PubMed

    Hayashi, Shimpei; Kuramata, Masato; Abe, Tadashi; Takagi, Hiroki; Ozawa, Kenjirou; Ishikawa, Satoru

    2017-09-01

    Reduction of the level of arsenic (As) in rice grains is an important challenge for agriculture. A recent study reported that the OsABCC1 transporter prevents the accumulation of As in grains by sequestering As-phytochelatin complexes into vacuoles in the upper nodes. However, how phytochelatins are provided in response to As remains unclear. Here, we show that the phytochelatin synthase OsPCS1 plays a crucial role in reducing As levels in rice grains. Using a forward genetic approach, we isolated two rice mutants (has1 and has2) in which As levels were much higher in grains but significantly lower in node I compared with the wild type. Map-based cloning identified the genes responsible as OsABCC1 in has1 and OsPCS1 in has2. The levels of As in grains and node I were similar between the two mutants, suggesting that OsABCC1 preferentially cooperates with OsPCS1 to sequester As, although rice has another phytochelatin synthase, OsPCS2. An in vitro phytochelatin synthesis assay indicated that OsPCS1 was more sensitive to activation by As than by cadmium, whereas OsPCS2 was more weakly activated by As than by cadmium. Transgenic plants highly expressing OsPCS1 showed significantly lower As levels in grains than did wild-type plants. Our results provide new knowledge of the relative contribution of rice PCS paralogs to As sequestration and suggest a good candidate tool to reduce As levels in rice grains. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  8. Reduced levels of folate transporters (PCFT and RFC) in membrane lipid rafts result in colonic folate malabsorption in chronic alcoholism.

    PubMed

    Wani, Nissar Ahmad; Kaur, Jyotdeep

    2011-03-01

    We studied the effect of chronic ethanol ingestion on folate transport across the colonic apical membranes (CAM) in rats. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20%) solution orally for 3 months and folate transport was studied in the isolated colon apical membrane vesicles. The folate transport was found to be carrier mediated, saturable, with pH optima at 5.0. Chronic ethanol ingestion reduced the folate transport across the CAM by decreasing the affinity of transporters (high Km) for the substrate and by decreasing the number of transporter molecules (low Vmax) on the colon luminal surface. The decreased transport activity at the CAM was associated with down-regulation of the proton-coupled folate transporter (PCFT) and the reduced folate carrier (RFC) which resulted in decreased PCFT and RFC protein levels in the colon of rats fed alcohol chronically. Moreover, the PCFT and the RFC were found to be distributed in detergent insoluble fraction of the CAM in rats. Floatation experiments on Optiprep density gradients demonstrated the association of the PCFT and the RFC protein with lipid rafts (LR). Chronic alcoholism decreased the PCFT and the RFC protein levels in the CAM LR in accordance with the decreased synthesis. Hence, we propose that downregulation in the expression of the PCFT and the RFC in colon results in reduced levels of these transporters in colon apical membrane LR as a mechanism of folate malabsorption during chronic alcoholism.

  9. Reduced pyrazinamidase activity and the natural resistance of Mycobacterium kansasii to the antituberculosis drug pyrazinamide.

    PubMed

    Sun, Z; Zhang, Y

    1999-03-01

    Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug that requires conversion to the bactericidal compound pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) activity of nicotinamidase to show activity against Mycobacterium tuberculosis. Mutations leading to a loss of PZase activity cause PZA resistance in M. tuberculosis. M. kansasii is naturally resistant to PZA and has reduced PZase activity along with an apparently detectable nicotinamidase activity. The role of the reduction in PZase activity in the natural PZA resistance of M. kansasii is unknown. The MICs of PZA and POA for M. kansasii were determined to be 500 and 125 micrograms/ml, respectively. Using [14C]PZA and [14C]nicotinamide, we found that M. kansasii had about 5-fold-less PZase activity and about 25-fold-less nicotinamidase activity than M. tuberculosis. The M. kansasii pncA gene was cloned on a 1.8-kb BamHI DNA fragment, using M. avium pncA probe. Sequence analysis showed that the M. kansasii pncA gene encoded a protein with homology to its counterparts from M. tuberculosis (69.9%), M. avium (65.6%), and Escherichia coli (28.5%). Transformation of naturally PZA-resistant M. bovis BCG with M. kansasii pncA conferred partial PZA susceptibility. Transformation of M. kansasii with M. avium pncA caused functional expression of PZase and high-level susceptibility to PZA, indicating that the natural PZA resistance in M. kansasii results from a reduced PZase activity. Like M. tuberculosis, M. kansasii accumulated POA in the cells at an acidic pH; however, due to its highly active POA efflux pump, the naturally PZA-resistant species M. smegmatis did not. These findings suggest the existence of a weak POA efflux mechanism in M. kansasii.

  10. Active Supervision: An Intervention to Reduce High School Tardiness

    ERIC Educational Resources Information Center

    Johnson-Gros, Kristin N.; Lyons, Elizabeth A.; Griffin, Jennifer R.

    2008-01-01

    One proactive approach to aid in reducing disciplinary problems in schools is implementing Positive Behavior Support (PBS) strategies. To successfully implement PBS school-wide, Sugai and Horner (2002a) emphasize a multisystems perspective, which focuses on school-wide discipline, classroom management, non-classroom settings, and individual…

  11. Active Supervision: An Intervention to Reduce High School Tardiness

    ERIC Educational Resources Information Center

    Johnson-Gros, Kristin N.; Lyons, Elizabeth A.; Griffin, Jennifer R.

    2008-01-01

    One proactive approach to aid in reducing disciplinary problems in schools is implementing Positive Behavior Support (PBS) strategies. To successfully implement PBS school-wide, Sugai and Horner (2002a) emphasize a multisystems perspective, which focuses on school-wide discipline, classroom management, non-classroom settings, and individual…

  12. 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.

  13. 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.

  14. Tissue Plasminogen Activator Reduces Neurological Damage after Cerebral Embolism

    NASA Astrophysics Data System (ADS)

    Zivin, Justin A.; Fisher, Marc; Degirolami, Umberto; Hemenway, Carl C.; Stashak, Joan A.

    1985-12-01

    Intravenous administration of tissue plasminogen activator immediately after the injection of numerous small blood clots into the carotid circulation in rabbit embolic stroke model animals caused a significant reduction in neurological damage. In vitro studies indicate that tissue plasminogen activator produced substantial lysis of clots at concentrations comparable to those expected in vivo, suggesting that this may be the mechanism of action of this drug. Drug-induced hemorrhages were not demonstrable. Tissue plasminogen activator may be of value for the immediate treatment of embolic stroke.

  15. 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

  16. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    PubMed Central

    Jokeit, Hennric; Okujava, Michael; Woermann, Friedrich G

    2001-01-01

    Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry) influences the blood oxygenation level dependent (BOLD) contrast changes induced by neuronal activation and measured by functional MRI (fMRI). We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE). Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL) activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P < 0.001). Activation over the supposedly normal MTL, i.e. contralateral to the seizure onset of TLE patients, was smaller than the averaged MTL activation in healthy controls (P < 0.005). Age, duration of epilepsy, side of seizure onset, and intelligence were not correlated to the extent of the significant BOLD-response over both MTL in patients with TLE. Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy. PMID:11710962

  17. 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.

  18. Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

    PubMed

    DeSmet, Marsha L; Fleet, James C

    2017-01-16

    High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH)2D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH)2D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH)2D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH)2D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention.

  19. Effects of reduced levels of sulfite in wine production using mixtures with lysozyme and dimethyl dicarbonate on levels of volatile and biogenic amines.

    PubMed

    Ancín-Azpilicueta, Carmen; Jiménez-Moreno, Nerea; Moler, José Antonio; Nieto-Rojo, Rodrigo; Urmeneta, Henar

    2016-10-01

    Sulphur dioxide (SO2) is an important preservative for wine, but its presence in foods can cause allergies and this has given impetus to the research for alternatives. The aim of this study was to reduce levels of sulfite in wine production using mixtures with lysozyme and dimethyl dicarbonate and examine the influence on levels of volatile and biogenic amines. To do so, vinifications were carried out using lysozyme, dimethyl dicarbonate (DMDC) and mixtures of these with SO2 in different concentrations (25 and 50 mg l(-1)). Results were compared with a control vinification with only SO2 (50 mg l(-1)). Mixing low concentrations of SO2 with lysozyme and DMDC reduced the concentration of biogenic amines (histamine, tyramine, putrescine, cadaverine, phenylethylamine + spermidine and spermine). In general, the total concentration of volatile amines (dimethylamine, isopropylamine, isobutylamine, pyrrolidine, ethylamine, diethylamine, amylamine and hexylamine) was higher in the sample fermented only with SO2. The concentrations of amines with secondary amino groups (dimethylamine, diethylamine, pyrrolidine) were higher in the sample only fermented with SO2 than those fermented with DMDC and lysozyme or with a mixture of preservatives. When SO2 was the only preservative in wine, total amine concentration (biogenic and volatile amines) was higher than for the rest of the treatments. Lysozyme by itself, and lysozyme mixed with SO2, both reduced the formation of biogenic amines but given the antioxidant activity of SO2 the use of the preservative mixture seems more advisable.

  20. Endurance Exercise Reduces Hepatic Fat Content and Serum Fibroblast Growth Factor 21 Levels in Elderly Men.

    PubMed

    Taniguchi, Hirokazu; Tanisawa, Kumpei; Sun, Xiaomin; Kubo, Takafumi; Higuchi, Mitsuru

    2016-01-01

    Age-related hepatic fat accumulation increases the risk of cardiometabolic diseases, and the fibroblast growth factor (FGF) 21-resistant state caused by fatty liver underlies the pathogenesis of these diseases. Previous studies suggested that a higher level of cardiorespiratory fitness was associated with both lower hepatic fat content and serum FGF21 levels; however, the effect of endurance exercise on hepatic fat content and serum FGF21 concentration has not been studied. Therefore, we aimed to elucidate whether endurance exercise reduced hepatic fat content and serum FGF21 levels. This is a randomized crossover trial. The study setting was an institutional practice. Thirty-three elderly Japanese men participated in the study. The intervention was a 5-week endurance exercise program comprising three cycle ergometer sessions per week. Hepatic fat content was assessed by proton magnetic resonance spectroscopy, and serum FGF21 level was determined by ELISA. A 5-week endurance exercise program decreased the hepatic fat content and serum FGF21 levels without weight loss, and the changes were higher in the exercise period than in the control period (P = .021 and P = .026, respectively). Correlation analysis demonstrated that only the change in hepatic fat content was significantly and positively correlated with change in serum FGF21 levels (r = 0.366, P = .006). A 5-week endurance exercise program decreased hepatic fat content and serum FGF21 levels without weight loss in elderly men, and exercise-induced hepatic fat reduction mediated the reduction in serum FGF21 levels. These findings suggest that endurance exercise modulates hepatic fat content and FGF21 resistance, regardless of obesity status.

  1. Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids

    PubMed Central

    Cardoso, Henriqueta D.; Passos, Priscila P.; Lagranha, Claudia J.; Ferraz, Anete C.; Santos Júnior, Eraldo F.; Oliveira, Rafael S.; Oliveira, Pablo E. L.; Santos, Rita de C. F.; Santana, David F.; Borba, Juliana M. C.; Rocha-de-Melo, Ana P.; Guedes, Rubem C. A.; Navarro, Daniela M. A. F.; Santos, Geanne K. N.; Borner, Roseane; Picanço-Diniz, Cristovam W.; Beltrão, Eduardo I.; Silva, Janilson F.; Rodrigues, Marcelo C. A.; Andrade da Costa, Belmira L. S.

    2012-01-01

    Oxidative stress (OS) has been implicated in the etiology of certain neurodegenerative disorders. Some of these disorders have been associated with unbalanced levels of essential fatty acids (EFA). The response of certain brain regions to OS, however, is not uniform and a selective vulnerability or resilience can occur. In our previous study on rat brains, we observed that a two-generation EFA dietary restriction reduced the number and size of dopaminergic neurons in the substantia nigra (SN) rostro-dorso-medial. To understand whether OS contributes to this effect, we assessed the status of lipid peroxidation (LP) and anti-oxidant markers in both SN and corpus striatum (CS) of rats submitted to this dietary treatment for one (F1) or two (F2) generations. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. LP was measured using the thiobarbituric acid reaction method (TBARS) and the total superoxide dismutase (t-SOD) and catalase (CAT) enzymatic activities were assessed. The experimental diet significantly reduced the docosahexaenoic acid (DHA) levels of SN phospholipids in the F1 (~28%) and F2 (~50%) groups. In F1 adult animals of the experimental group there was no LP in both SN and CS. Consistently, there was a significant increase in the t-SOD activity (p < 0.01) in both regions. In EF2 young animals, degeneration in dopaminergic and non-dopaminergic neurons and a significant increase in LP (p < 0.01) and decrease in the CAT activity (p < 0.001) were detected in the SN, while no inter-group difference was found for these parameters in the CS. Conversely, a significant increase in t-SOD activity (p < 0.05) was detected in the CS of the experimental group compared to the control. The results show that unbalanced EFA dietary levels reduce the redox balance in the SN and reveal mechanisms of resilience in the CS under this stressful condition. PMID

  2. Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids.

    PubMed

    Cardoso, Henriqueta D; Passos, Priscila P; Lagranha, Claudia J; Ferraz, Anete C; Santos Júnior, Eraldo F; Oliveira, Rafael S; Oliveira, Pablo E L; Santos, Rita de C F; Santana, David F; Borba, Juliana M C; Rocha-de-Melo, Ana P; Guedes, Rubem C A; Navarro, Daniela M A F; Santos, Geanne K N; Borner, Roseane; Picanço-Diniz, Cristovam W; Beltrão, Eduardo I; Silva, Janilson F; Rodrigues, Marcelo C A; Andrade da Costa, Belmira L S

    2012-01-01

    Oxidative stress (OS) has been implicated in the etiology of certain neurodegenerative disorders. Some of these disorders have been associated with unbalanced levels of essential fatty acids (EFA). The response of certain brain regions to OS, however, is not uniform and a selective vulnerability or resilience can occur. In our previous study on rat brains, we observed that a two-generation EFA dietary restriction reduced the number and size of dopaminergic neurons in the substantia nigra (SN) rostro-dorso-medial. To understand whether OS contributes to this effect, we assessed the status of lipid peroxidation (LP) and anti-oxidant markers in both SN and corpus striatum (CS) of rats submitted to this dietary treatment for one (F1) or two (F2) generations. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. LP was measured using the thiobarbituric acid reaction method (TBARS) and the total superoxide dismutase (t-SOD) and catalase (CAT) enzymatic activities were assessed. The experimental diet significantly reduced the docosahexaenoic acid (DHA) levels of SN phospholipids in the F1 (~28%) and F2 (~50%) groups. In F1 adult animals of the experimental group there was no LP in both SN and CS. Consistently, there was a significant increase in the t-SOD activity (p < 0.01) in both regions. In EF2 young animals, degeneration in dopaminergic and non-dopaminergic neurons and a significant increase in LP (p < 0.01) and decrease in the CAT activity (p < 0.001) were detected in the SN, while no inter-group difference was found for these parameters in the CS. Conversely, a significant increase in t-SOD activity (p < 0.05) was detected in the CS of the experimental group compared to the control. The results show that unbalanced EFA dietary levels reduce the redox balance in the SN and reveal mechanisms of resilience in the CS under this stressful condition.

  3. Erythrocyte aldose reductase activity and sorbitol levels in diabetic retinopathy

    PubMed Central

    Satyanarayana, A.; Balakrishna, N.; Ayyagari, Radha; Padma, M.; Viswanath, K.; Petrash, J. Mark

    2008-01-01

    Purpose Activation of polyol pathway due to increased aldose reductase (ALR2) activity has been implicated in the development of diabetic complications including diabetic retinopathy (DR), a leading cause of blindness. However, the relationship between hyperglycemia-induced activation of polyol pathway in retina and DR is still uncertain. We investigated the relationship between ALR2 levels and human DR by measuring ALR2 activity and its product, sorbitol, in erythrocytes. Methods We enrolled 362 type 2 diabetic subjects (T2D) with and without DR and 66 normal subjects in this clinical case-control study. Clinical evaluation of DR in T2D patients was done by fundus examination. ALR2 activity and sorbitol levels along with glucose and glycosylated hemoglobin (HbA1C) levels in erythrocytes were determined. Results T2D patients with DR showed significantly higher specific activity of ALR2 as compared to T2D patients without DR. Elevated levels of sorbitol in T2D patients with DR, as compared to T2D patients without DR, corroborated the increased ALR2 activity in erythrocytes of DR patients. However, the increased ALR2 activity was not significantly associated with diabetes duration, age, and HbA1C in both the DR group and total T2D subjects. Conclusions Levels of ALR2 activity as well as sorbitol in erythrocytes may have value as a quantitative trait to be included among other markers to establish a risk profile for development of DR. PMID:18385795

  4. 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.

  5. CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells.

    PubMed

    Carter, Clive R D; Aravind, Ganesha; Smalle, Natuley L; Cole, June Y; Savic, Sinisa; Wood, Philip M D

    2013-02-01

    Common variable immunodeficiency (CVID) is a primary antibody immunodeficiency with approximately 20% of patients reporting additional autoimmune symptoms. The primary aim of this study was to compare the levels of activated and regulatory T cells (Treg cells) in CVID patients in an attempt to clarify their possible interactions leading to the generation of autoimmunity. Immunophenotyping of T cells was performed by flow cytometry using a whole blood approach. Surface expression of human leukocyte antigen HLA class II DR and intracellular levels of granzyme B in T cell subsets were assessed; Treg levels were measured using CD4 CD25, FOXp3 and CTLA-4. CVID patients had higher levels of granzyme B and HLA-DR on CD8(+) T cells compared with control values (mean of 59% vs 30% and 45% vs 21%, respectively). Patients also had reduced levels of Treg cells compared with control values (con mean=3.24% vs pat=2.54%). Patients with autoimmunity (5/23) had a similar level of T cell activation markers to the rest of the patients but with lower Treg cells (mean of 1.1%) and reduced CD25 and CTLA-4 expression. Patients with autoimmunity had a higher ratio of activated to Treg cells compared with patients with no autoimmune symptoms. These results highlight that reduced levels of Treg cells were associated with elevated levels of activated T cells, suggesting that reduced Treg cells in these patients may have functional consequences in allowing exaggerated T cell responses.

  6. 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

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

    PubMed

    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.

  8. Reducing levels of toxic chemicals in cigarette smoke: a new Healthy People 2010 objective.

    PubMed

    Richter, Patricia; Pechacek, Terry; Swahn, Monica; Wagman, Victoria

    2008-01-01

    We developed and implemented a national surveillance system to monitor and reduce the levels of toxicchemicals in tobacco smoke. A developmental Healthy People 2010 (HP 2010) objective was revised to report on levels of three categories of chemicals--tobacco-specific nitrosamines, polyaromatic hydrocarbons, and volatile organic compounds--in the smoke of leading U.S. cigarette brands. Unit-based sales-weighted average levels were calculated for each chemical category. The target for the new HP 2010 objective is a 10% reduction in unit-based sales-weighted average levels of each chemical category. The Centers for Disease Control and Prevention provided the baseline, target data, and laboratory analyses. A national data source, national baseline data, and target were presented to the Healthy People Steering Committee during 2005 Midcourse Review. Approval of the revised objective initiated the surveillance of three major classes of toxic chemicals in cigarette smoke. The approved objective provides a feasible, innovative approach for monitoring and supporting measurable population-based reductions in levels of toxic and carcinogenic chemicals in tobacco smoke.

  9. Changes in rabbit jaw-muscle activity parameters in response to reduced masticatory load.

    PubMed

    Grünheid, T; Brugman, P; Zentner, A; Langenbach, G E J

    2010-03-01

    Mechanical food properties influence the neuromuscular activity of jaw-closing muscles during mastication. It is, however, unknown how the activity profiles of the jaw muscles are influenced by long-term alterations in masticatory load. In order to elucidate the effect of reduced masticatory load on the daily habitual activity profiles of three functionally different jaw muscles, the electromyograms of the masseter, temporalis and digastric muscles were recorded telemetrically in 16 male rabbits between seven and 20 weeks of age. Starting at eight weeks of age the experimental animals were fed significantly softer pellets than the control animals. Daily muscle activity was quantified by the relative duration of muscle use (duty time), burst number and burst length in relation to multiple activity levels. The daily duty time and burst number of the masseter muscle were significantly lower in the experimental group than in the control group at 5% and 10% of the maximum activity during the two weeks following the change in food hardness. By contrast, altered food hardness did not significantly influence the activity characteristics of the temporalis and digastric muscles. The findings suggest that a reduction in masticatory load decreases the neuromuscular activity of the jaw-closing muscles that are primarily responsible for force generation during mastication. This decrease is most pronounced in the weeks immediately following the change in food hardness and is limited to the activity levels that reflect muscle contractions during chewing. These findings support the conclusion that the masticatory system manifests few diet-specific long-term changes in the activity profiles of jaw muscles.

  10. Reducing surgical levels by paraspinal mapping and diffusion tensor imaging techniques in lumbar spinal stenosis.

    PubMed

    Chen, Hua-Biao; Wan, Qi; Xu, Qi-Feng; Chen, Yi; Bai, Bo

    2016-04-25

    Correlating symptoms and physical examination findings with surgical levels based on common imaging results is not reliable. In patients who have no concordance between radiological and clinical symptoms, the surgical levels determined by conventional magnetic resonance imaging (MRI) and neurogenic examination (NE) may lead to a more extensive surgery and significant complications. We aimed to confirm that whether the use of diffusion tensor imaging (DTI) and paraspinal mapping (PM) techniques can further prevent the occurrence of false positives with conventional MRI, distinguish which are clinically relevant from levels of cauda equina and/or nerve root lesions based on MRI, and determine and reduce the decompression levels of lumbar spinal stenosis than MRI + NE, while ensuring or improving surgical outcomes. We compared the data between patients who underwent MRI + (PM or DTI) and patients who underwent conventional MRI + NE to determine levels of decompression for the treatment of lumbar spinal stenosis. Outcome measures were assessed at 2 weeks, 3 months, 6 months, and 12 months postoperatively. One hundred fourteen patients (59 in the control group, 54 in the experimental group) underwent decompression. The levels of decompression determined by MRI + (PM or DTI) in the experimental group were significantly less than that determined by MRI + NE in the control group (p = 0.000). The surgical time, blood loss, and surgical transfusion were significantly less in the experimental group (p = 0.001, p = 0.011, p = 0.001, respectively). There were no differences in improvement of the visual analog scale back and leg pain (VAS-BP, VAS-LP) scores and Oswestry Disability Index (ODI) scores at 2 weeks, 3 months, 6 months, and 12 months after operation between the experimental and control groups. MRI + (PM or DTI) showed clear benefits in determining decompression levels of lumbar spinal stenosis than MRI + NE. In patients with lumbar spinal

  11. 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.

  12. Accumulation of high OPDA level correlates with reduced ROS and elevated GSH benefiting white cell survival in variegated leaves

    PubMed Central

    Sun, Ying-Hsuan; Hung, Chiu-Yueh; Qiu, Jie; Chen, Jianjun; Kittur, Farooqahmed S.; Oldham, Carla E.; Henny, Richard J.; Burkey, Kent O.; Fan, Longjiang; Xie, Jiahua

    2017-01-01

    Variegated ‘Marble Queen’ (Epipremnum aureum) plant has white (VMW) and green (VMG) sectors within the same leaf. The white sector cells containing undifferentiated chloroplasts are viable, but the underlying mechanism for their survival and whether these white cells would use any metabolites as signal molecules to communicate with the nucleus for maintaining their viability remain unclear. We analyzed and compared phytohormone levels with their precursors produced in chloroplasts between VMW and VMG, and further compared their transcriptomes to understand the consequences related to the observed elevated 12-oxo phytodienoic acid (OPDA), which was 9-fold higher in VMW than VMG. Transcriptomic study showed that a large group of OPDA-responsive genes (ORGs) were differentially expressed in VMW, including stress-related transcription factors and genes for reactive oxygen species (ROS) scavengers, DNA replication and repair, and protein chaperones. Induced expression of these ORGs could be verified in OPDA-treated green plants. Reduced level of ROS and higher levels of glutathione in VMW were further confirmed. Our results suggest that elevated OPDA or its related compounds are recruited by white cells as a signaling molecule(s) to up-regulate stress and scavenging activity related genes that leads to reduced ROS levels and provides survival advantages to the white cells. PMID:28276518

  13. 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.

  14. 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

  15. Longitudinal Floating Ice Control Structures: A New Concept for Reducing Ice Jam Flood Levels

    DTIC Science & Technology

    1990-09-01

    friction factor is taken as 1.25 based on data from several ice jams I % . ( Beltaos 1983), and the ice properties g = 1.2 and S , = 0.92 are held...as much as Beltaos , S . (1983) River ice jams: Theory, case 8 studies, and applications. Journal of the Hydraulics sign. Journal of Waterway, Port...DOTIC S NOV 15 1990O. 0’~’FL P Longitudinal Floating Ice Control Structures A New Concept for Reducing Ice Jam Flood Levels 00NDarryl J. Calkins

  16. 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.

  17. Levetiracetam reduces abnormal network activations in temporal lobe epilepsy

    PubMed Central

    Wandschneider, Britta; Stretton, Jason; Sidhu, Meneka; Centeno, Maria; Kozák, Lajos R.; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

    2014-01-01

    Objective: We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). Methods: In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. Results: We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. Conclusions: Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. Classification of evidence: This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures. PMID:25253743

  18. Exercise training reduces PGE2 levels and induces recovery from steatosis in tumor-bearing rats.

    PubMed

    Lira, F S; Yamashita, A; Carnevali, L C; Gonçalves, D C; Lima, W P; Rosa, J C; Caperuto, E C; Rosa, L F C; Seelaender, M

    2010-12-01

    The effects of endurance training on PGE (2) levels and upon the maximal activity of hepatic carnitine palmitoyltransferase (CPT) system were studied in rats bearing the Walker 256 carciosarcoma. Animals were randomly assigned to a sedentary control (SC), sedentary tumor-bearing (ST), exercised control (EC), and as an exercised tumor-bearing (ET) group. Trained rats ran on a treadmill (60% VO (2) max) for 60 min/day, 5 days/week, for 8 weeks. We examined the mRNA expression (RT-PCR) and maximal activity (radioassay) of the carnitine palmitoyltransferase system enzymes (CPT I and CPT II), as well as the gene expression of fatty-acid-binding protein (L-FABP) in the liver. PGE (2) content was measured in the serum, in tumor cells, and in the liver (ELISA). CPT I and CPT II maximal activity were decreased (p<0.01) in ST when compared with SC. In contrast, serum PGE (2) was increased (p<0.05) in cachectic animals as compared with SC. In the liver, PGE (2) content was also increased (p<0.05) when compared with SC. Endurance training restored maximal CPT I and CPT II activity in the tumor-bearing animals (p<0.0001). Exercise training induced PGE (2) levels to return to control values in the liver of tumor-bearing training rats (p<0.05) and decreased the eicosanoid content in the tumor (p<0.01). In conclusion, endurance training was capable of reestablishing liver carnitine palmitoyltransferase (CPT) system activity associated with decreased PGE (2) levels in cachectic tumor-bearing animals, preventing steatosis.

  19. Do Productive Activities Reduce Inflammation in Later Life? Multiple Roles, Frequency of Activities, and C-Reactive Protein

    PubMed Central

    Kim, Seoyoun; Ferraro, Kenneth F.

    2014-01-01

    Purpose of the Study: The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. Design and Methods: The study uses a representative survey of adults aged 57–85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Results: Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Implications: Productive activities—and frequent volunteering in particular—may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. PMID:23969258

  20. 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. © 2014 John Wiley & Sons Ltd.

  1. 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.

  2. Synthetic pheromones as a management technique - dispensers reduce Linepithema humile activity in a commercial vineyard.

    PubMed

    Westermann, Fabian L; Bell, Vaughn A; Suckling, David M; Lester, Philip J

    2016-04-01

    Invasive ants, such as the Argentine ant, have often been reported to facilitate honeydew-producing hemipteran pests such as mealybugs, which can be vectors of plant pathogens. Synthetic pheromones may offer a target-specific method to control such ants and consequently lower the abundance of honeydew-producing pests. Here we report the results of a trial to suppress Argentine ants in grapevines using ant pheromone dispensers. Compared with untreated controls, we observed a significant drop in Argentine ant activity on the ground, irrespective of whether pheromone dispensers were placed at ground level, within the canopy or in both locations. Ant counts in the canopy confirmed that Argentine ant abundance was reduced under the influence of the pheromone dispenser placed at ground level compared with untreated controls. However, placing dispensers only in the canopy did not reduce the numbers of ants within the canopy compared with untreated controls. Our results showed that pheromone dispensers can significantly reduce Argentine ant foraging in grapevines if they are positioned appropriately. This technique could potentially reduce the abundance of associated mealybugs and potentially attendant virus vectoring areawide. © 2015 Society of Chemical Industry.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  4. 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

  5. Heavy metals chromium and neodymium reduced phosphorylation level of heat shock protein 27 in human keratinocytes.

    PubMed

    Zhang, Qihao; Zhang, Lei; Xiao, Xue; Su, Zhijian; Zou, Ping; Hu, Hao; Huang, Yadong; He, Qing-Yu

    2010-06-01

    Heavy metals may exert their acute and chronic effects on the human skin through stress signals. In the present study, 2DE-based proteomics was used to analyze the protein expression in human keratinocytes exposed to heavy metals, chromium and neodymium, and 10 proteins with altered expression were identified. Among these proteins, small heat shock protein 27 (HSP27) was up-regulated significantly and the up-regulation was validated by Western blot and immunofluorescence. In addition, the mRNA expression level of HSP27 markedly increased as detected by quantitative PCR. More interestingly, the ratio of phosphorylated HSP27 and total HSP27 significantly decreased in keratinocytes treated with the heavy metals. These findings suggested that heavy metals reduced the phosphorylation level of HSP27, and that the ratio of p-HSP27 and HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products.

  6. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  7. 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.

  8. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour

    PubMed Central

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats. PMID:22666534

  9. Evidence of the activity of dissimilatory sulfate-reducing prokaryotes in nonsulfidogenic tropical mobile muds.

    PubMed

    Madrid, Vanessa M; Aller, Robert C; Aller, Josephine Y; Chistoserdov, Andrei Y

    2006-08-01

    In spite of the nonsulfidic conditions and abundant reactive iron(III) commonly found in mobile tropical deltaic muds, genes encoding dissimilatory sulfite reductase (dsr) were successfully amplified from the upper approximately 1 m of coastal deposits sampled along French Guiana and in the Gulf of Papua. The dsr sequences retrieved were highly diverse, were generally represented in both study regions and fell into six large phylogenetic groupings: Deltaproteobacteria, Thermodesulfovibrio groups, Firmicutes and three groups without known cultured representatives. The spatial and temporal distribution of dsr sequences strongly supports the contention that the sulfate-reducing prokaryote communities in mobile mud environments are cosmopolitan and stable over a period of years. The decrease in the (35)SO(4) (2-) tracer demonstrates that, despite abundant reactive sedimentary iron(III) ( approximately 350-400 mumol g(-1)), the sulfate-reducing prokaryotes present are active, with the highest levels of sulfide being generated in the upper zones of the cores (0-30 cm). Both the time course of the (35)S-sulfide tracer activity and the lack of reduced sulfur in sediments demonstrate virtually complete anaerobic loss of solid phase sulfides. We propose a pathway of organic matter oxidation involving at least 5-25% of the remineralized carbon, wherein sulfide produced by sulfate-reducing prokaryotes is cyclically oxidized biotically or abiotically by metal oxides.

  10. Reduced cholesterol levels in African-American adults with sickle cell disease.

    PubMed Central

    Shores, Jaimie; Peterson, John; VanderJagt, Dorothy; Glew, Robert H.

    2003-01-01

    In a recent study of boys and girls with sickle cell disease (SCD) in Nigeria, a common finding with this genetic hematologic disorder was a marked reduction in total cholesterol. Epidemiologic studies have identified a relation between low serum levels of total cholesterol (< 130 mg/dL) and increased mortality from all causes. We were interested in knowing if hypocholesterolemia was present in African-American adults with SCD. We therefore compared the plasma lipid profiles of the 16 men and 20 women with SCD who received care at the University of Texas Medical Branch at Galveston between 1996 and 2001 with those of 2,415 gender-matched African Americans who were seen at the same hospital but who did not have SCD. The age-adjusted mean total cholesterol concentrations of the SCD males and females were 147 +/- 42 mg/dL and 179 +/- 36 mg/dL, compared to male and female control values of 200 +/- 75 mg/dL and 216 +/- 61 mg/dL, respectively. These differences between SCD subjects and controls were statistically significant (p < 0.001). The LDL-cholesterol levels of the men and women with SCD (68 +/- 28 mg/dl and 95 +/- 33 mg/dl, respectively) were also significantly reduced relative to the controls (121 +/- 58 mg/dl and 128 +/- 54 mg/dl, respectively, p = 0.001). The triglyceride levels of the men with SCD were much reduced relative to the male controls (102 +/- 34 mg/dL versus 194 +/- 215 mg/dL, p = 0.02), but were not different between the SCD females and their control group. The HDL-cholesterol levels of the SCD subjects and the controls were not different. These results indicate that total cholesterol and LDL-cholesterol concentrations are significantly reduced in adult men and women with SCD in the United States, and should heighten interest in the implication that low levels of cholesterol might exacerbate the medical problems inherent in this genetic disease. PMID:14527048

  11. 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…

  12. 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…

  13. Effectiveness of ionizing radiation in reducing furan and acrylamide levels in foods.

    PubMed

    Fan, Xuetong; Mastovska, Katerina

    2006-10-18

    Furan and acrylamide are two possible carcinogens commonly found in many thermally processed foods. The possibility of using ionizing radiation to reduce the levels of thermally induced furan and acrylamide in water and selected foods was investigated. Aqueous furan solutions, and foods (frankfurters, sausages, infant sweet potatoes) that contained furan were irradiated to various doses of gamma-rays. Water and oil spiked with acrylamide and potato chips (a known acrylamide-containing food) were also irradiated. In addition, possible irradiation-induced formation of acrylamide in glucose and asparagine solutions was analyzed. Results showed that irradiation at 1.0 kGy destroyed almost all furan in water. In frankfurters, sausages, and infant sweet potatoes, the rate of irradiation-induced destruction of furan was much lower than the rate in water, although significant reductions in furan levels were observed in all foods. Irradiation at 2.5-3.5 kGy, doses that can inactivate 5-log of most common pathogens, reduced furan levels in the food samples by 25-40%. Similarly to furan, acrylamide in water was also sensitive to irradiation. After 1.5 kGy of irradiation, most of the acrylamide was degraded. Irradiation, however, had a very limited effect on acrylamide levels in oil and in potato chips, even at a dose of 10 kGy. No detectable acrylamide was formed in the mixture of asparagine and glucose upon irradiation. These results suggest that a low dose of irradiation easily destroys furan and acrylamide in water. In real foods, however, the reduction of furan was less effective than in water, whereas the reduction in acrylamide was minimal.

  14. The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates reduced levels of hexadecatrienoic acid.

    PubMed

    Afitlhile, Meshack; Duffield-Duncan, Kayla; Fry, Morgan; Workman, Samantha; Hum-Musser, Sue; Hildebrand, David

    2015-11-01

    A null and heterozygous mutant for the Arabidopsis thaliana TOC132 and TOC120 genes accumulates increased levels of 16:0 and decreased 16:3, suggesting altered homeostasis in fatty acid synthesis. The FAD5 gene encodes a plastid desaturase that catalyzes the first step in the synthesis of 16:3 in monogalactosyldiacylglycerol (MGDG). In non-acclimated toc132toc120+/- mutant plants, the FAD5 gene was repressed and this correlated with decreased levels of 16:3. In cold-acclimated mutant however, the FAD5 gene was upregulated and there was a small increase in 16:3 levels relative to the non-acclimated mutant plants. The MGD1 gene was expressed at control levels and the mutant accumulated levels of MGDG that were similar to the wild type. In the mutant however, MGDG had decreased 16:3 levels, suggesting that the activity of FAD5 desaturase was compromised. In the mutant, the FAD2 and FAD3 genes were downregulated but levels of 18:3-PC were increased, suggesting posttranscriptional regulation for the ER-localized fatty acid desaturases. The Toc120 or Toc159 receptor is likely to compensate for a defective Toc132 receptor. In the cold-acclimated mutant, the TOC159 gene was repressed ca. 300-fold, whereas the TOC120 gene was repressed 7-fold relative to the non-acclimated wild type. Thus, the TOC159 gene is more sensitive to cold-stress and might not compensate for defect in the TOC132 gene under these conditions. Overall, these data show that a mutation in the TOC132 gene results in decreased 16:3 levels, indicating the need for an intact Toc132/Toc120 receptor, presumably to facilitate the import of the FAD5 preprotein into chloroplasts.

  15. 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

  16. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 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

  18. Cerium Oxide Nanoparticles Reduce Microglial Activation and Neurodegenerative Events in Light Damaged Retina.

    PubMed

    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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Melatonin and selenium reduce plasma cytokine and brain oxidative stress levels in diabetic rats.

    PubMed

    Kahya, Mehmet Cemal; Naziroğlu, Mustafa; Çiğ, Bilal

    2015-01-01

    Hyperglycaemia-induced progression of brain and erythrocyte oxidative injuries might be modulated by melatonin and selenium as potent antioxidants. The present study was conducted to explore whether melatonin and selenium protect against diabetic brain and erythrocyte oxidative stress levels in streptozotocin (STZ)-induced diabetic rats. Seventy rats were equally divided into seven groups. The first and second groups were used as untreated and placebo treated controls. The third group was treated with STZ to induce diabetes. The fourth and sixth groups received 10 mg kg(-1) melatonin. The fifth and seventh groups were treated with 1.5 mg kg(-1) selenium (sodium selenite). The sixth and seventh groups were treated with STZ administered with melatonin and selenium as described for the fourth and fifth groups. Brain and erythrocyte lipid peroxidation levels and plasma IL-1β and IL-4 levels were high in the STZ group, although they were low in melatonin and selenium treatments. Decreased glutathione peroxidase, reduced glutathione, total antioxidant status, vitamins A and vitamin E values in brain and erythrocyte of STZ group were increased by melatonin and selenium treatments. Melatonin and selenium induced protective effects against diabetes-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production.

  4. Melatonin and selenium reduce plasma cytokine and brain oxidative stress levels in diabetic rats.

    PubMed

    Kahya, Mehmet Cemal; Naziroğlu, Mustafa; Çiğ, Bilal

    2015-08-05

    Hyperglycaemia-induced progression of brain and erythrocyte oxidative injuries might be modulated by melatonin and selenium as potent antioxidants. The present study was conducted to explore whether melatonin and selenium protect against diabetic brain and erythrocyte oxidative stress levels in streptozotocin (STZ)-induced diabetic rats. Seventy rats were equally divided into seven groups. The first and second groups were used as untreated and placebo treated controls. The third group was treated with STZ to induce diabetes. The fourth and sixth groups received 10 mg kg(-1) melatonin. The fifth and seventh groups were treated with 1.5 mg kg(-1) selenium (sodium selenite). The sixth and seventh groups were treated with STZ administered with melatonin and selenium as described for the fourth and fifth groups. Brain and erythrocyte lipid peroxidation levels and plasma IL-1β and IL-4 levels were high in the STZ group, although they were low in melatonin and selenium treatments. Decreased glutathione peroxidase, reduced glutathione, total antioxidant status, vitamins A and vitamin E values in brain and erythrocyte of STZ group were increased by melatonin and selenium treatments. Melatonin and selenium induced protective effects against diabetes-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production.

  5. 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

    2016-01-05

    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.

  6. Objective measurement of levels and patterns of physical activity.

    PubMed

    Riddoch, Chris J; Mattocks, Calum; Deere, Kevin; Saunders, Jo; Kirkby, Jo; Tilling, Kate; Leary, Sam D; Blair, Steven N; Ness, Andy R

    2007-11-01

    To measure the levels and patterns of physical activity, using accelerometers, of 11-year-old children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Cross-sectional analysis. ALSPAC is a birth cohort study located in the former county of Avon, in the southwest of England. This study used data collected when the children were 11 years old. 5595 children (2662 boys, 2933 girls). The children are the offspring of women recruited to a birth cohort study during 1991-2. The median age (95% CI) of the children is now 11.8 (11.6 to 11.9) years. Physical activity was measured over a maximum of 7 consecutive days using the MTI Actigraph accelerometer. Level and pattern of physical activity. The median physical activity level was 580 counts/min. Boys were more active than girls (median (IQR) 644 (528-772) counts/min vs 529 (444-638) counts/min, respectively). Only 2.5% (95% CI 2.1% to 2.9%) of children (boys 5.1% (95% CI 4.3% to 6.0%), girls 0.4% (95% CI 0.2% to 0.7%) met current internationally recognised recommendations for physical activity. Children were most active in summer and least active in winter (difference = 108 counts/min). Both the mother and partner's education level were inversely associated with activity level (p for trend <0.001 (both mother and partner)). The association was lost for mother's education (p for trend = 0.07) and attenuated for partner's education (p for trend = 0.02), after adjustment for age, sex, season, maternal age and social class. A large majority of children are insufficiently active, according to current recommended levels for health.

  7. Ceramides and Cell Signaling Molecules in Psoriatic Epidermis: Reduced Levels of Ceramides, PKC-α, and JNK

    PubMed Central

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

    2006-01-01

    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-α) 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-α 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-α 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

  8. 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

  9. Reduced frontal activation with increasing 2nd language proficiency.

    PubMed

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

    2009-11-01

    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 language. Native English speaking exchange students learning German were examined with functional magnetic resonance imaging while reading words in three different languages at two points in time: at the beginning of their stay (day 1) and 5 months later (day 2), when second language proficiency had significantly increased. On day 1, second language words evoked more frontal activation than words from the mother tongue. These differences were diminished on day 2. We therefore conclude that with increasing second language proficiency, lexico-semantic processing of second language words needs less frontal control. Our results demonstrate that lexico-semantic processing of first and second language converges onto similar networks as second language proficiency increases.

  10. 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.

  11. Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles.

    PubMed

    Priestley, Jessica R C; Buelow, Matthew W; McEwen, Scott T; Weinberg, Brian D; Delaney, Melanie; Balus, Sarah F; Hoeppner, Carlyn; Dondlinger, Lynn; Lombard, Julian H

    2013-09-01

    We investigated the effect of suppressing plasma angiotensin II (ANG II) levels on arteriolar relaxation in the hamster cheek pouch. Arteriolar diameters were measured via television microscopy during short-term (3-6days) high salt (HS; 4% NaCl) diet and angiotensin converting enzyme (ACE) inhibition with captopril (100mg/kg/day). ACE inhibition and/or HS diet eliminated endothelium-dependent arteriolar dilation to acetylcholine, endothelium-independent dilation to the NO donor sodium nitroprusside, the prostacyclin analogs carbacyclin and iloprost, and the KATP channel opener cromakalim; and eliminated arteriolar constriction during KATP channel blockade with glibenclamide. Scavenging of superoxide radicals and low dose ANG II infusion (25ng/kg/min, subcutaneous) reduced oxidant stress and restored arteriolar dilation in arterioles of HS-fed hamsters. Vasoconstriction to topically-applied ANG II was unaffected by HS diet while arteriolar responses to elevation of superfusion solution PO2 were unaffected (5% O2, 10% O2) or reduced (21% O2) by HS diet. These findings indicate that sustained exposure to low levels of circulating ANG II leads to widespread dysfunction in endothelium-dependent and independent vascular relaxation mechanisms in cheek pouch arterioles by increasing vascular oxidant stress, but does not potentiate O2- or ANG II-induced constriction of arterioles in the distal microcirculation of normotensive hamsters. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Phenobarbital specifically reduces gap junction protein mRNA level in rat liver.

    PubMed

    Mesnil, M; Fitzgerald, D J; Yamasaki, H

    1988-01-01

    The gene expression of liver major gap junction (GJ) protein was studied in rats systemically administered phenobarbital, a rat liver tumor promoter. Using a GJ protein cDNA and northern blot analysis, the level of GJ protein mRNA in liver was observed to be markedly reduced at 4 and 11 wk of phenobarbital exposure (0.1% in drinking water). However, the level of GJ protein mRNA was not altered in kidney at 11 wk of exposure. In liver, phenobarbital did not induce expression of the neoplasm-associated marker genes glutathione S-transferase (placental form) and gamma-glutamyltranspeptidase, while in kidney the observed expression of these genes was not changed. These in vivo results indicate that phenobarbital reduces GJ protein gene expression specifically in rat liver without altering expression of genes often altered during liver carcinogenesis, and they support assigning a role for the impairment of gap junctional intercellular communication in phenobarbital-mediated liver tumor promotion.

  13. Evaluation of household sanitizers for reducing levels of Escherichia coli on iceberg lettuce.

    PubMed

    Vijayakumar, Chitra; Wolf-Hall, Charlene E

    2002-10-01

    Diluted solutions of various household sanitizers (apple cider vinegar, white vinegar, bleach, and a reconstituted lemon juice product) were tested for their effectiveness in reducing counts of inoculated Escherichia coli and naturally present aerobic, mesophilic bacteria on lettuce. Sanitization treatments were carried out at 4 degrees C and at room temperature (ca. 21 degrees C) with and without agitation and at different exposure times (0, 1, 5, and 10 min). Of the sanitizers tested, 35% white vinegar (1.9% acetic acid) was the most effective in reducing E. coli levels (with a 5-log10 reduction after 5 min with agitation and after 10 min without agitation) and in reducing aerobic plate counts (with a >2-log10 reduction after 10 min with agitation). Lettuce samples treated with diluted household sanitizers were analyzed for consumer acceptability by sensory evaluation using a 9-point hedonic scale. The sanitized samples did not differ in acceptability (P > 0.05), except for samples treated with white vinegar. Samples treated with the white vinegar for 10 min were noticeably sour and slightly wilted in appearance. Consumer acceptability was maintained with all sanitization treatments, including those involving 35% white vinegar.

  14. 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.

  15. 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

  16. 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.

  17. 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…

  18. Children's Physical Activity Levels during Indoor Recess Dance Videos

    ERIC Educational Resources Information Center

    Erwin, Heather; Koufoudakis, Ryann; Beighle, Aaron

    2013-01-01

    Background: Children's physical activity (PA) levels remain low, and schools are being asked to assume a leadership role in PA promotion. Research suggests outdoor recess contributes to children's overall PA levels. However, similar research is not available for indoor recess, which occurs frequently due to a variety of factors. The purpose of…

  19. 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…

  20. 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…

  1. Children's Physical Activity Levels during Indoor Recess Dance Videos

    ERIC Educational Resources Information Center

    Erwin, Heather; Koufoudakis, Ryann; Beighle, Aaron

    2013-01-01

    Background: Children's physical activity (PA) levels remain low, and schools are being asked to assume a leadership role in PA promotion. Research suggests outdoor recess contributes to children's overall PA levels. However, similar research is not available for indoor recess, which occurs frequently due to a variety of factors. The purpose of…

  2. IL-19 Reduces Ligation-Mediated Neointimal Hyperplasia by Reducing Vascular Smooth Muscle Cell Activation

    PubMed Central

    Ellison, Stephen; Gabunia, Khatuna; Richards, James M.; Kelemen, Sheri E.; England, Ross N.; Rudic, Dan; Azuma, Yasu-Taka; Munroy, M. Alexandra; Eguchi, Satoru; Autieri, Michael V.

    2015-01-01

    We tested the hypothesis that IL-19, a putative member of the type 2 helper T-cell family of anti-inflammatory interleukins, can attenuate intimal hyperplasia and modulate the vascular smooth muscle cell (VSMC) response to injury. Ligated carotid artery of IL-19 knockout (KO) mice demonstrated a significantly higher neointima/intima ratio compared with wild-type (WT) mice (P = 0.04). More important, the increased neointima/intima ratio in the KO could be reversed by injection of 10 ng/g per day recombinant IL-19 into the KO mouse (P = 0.04). VSMCs explanted from IL-19 KO mice proliferated significantly more rapidly than WT. This could be inhibited by addition of IL-19 to KO VSMCs (P = 0.04 and P < 0.01). IL-19 KO VSMCs migrated more rapidly compared with WT (P < 0.01). Interestingly, there was no type 1 helper T-cell polarization in the KO mouse, but there was significantly greater leukocyte infiltrate in the ligated artery in these mice compared with WT. IL-19 KO VSMCs expressed significantly greater levels of inflammatory mRNA, including IL-1β, tumor necrosis factor α, and monocyte chemoattractant protein-1 in response to tumor necrosis factor α stimulation (P < 0.01 for all). KO VSMCs expressed greater adhesion molecule expression and adherence to monocytes. Together, these data indicate that IL-19 is a previously unrecognized counterregulatory factor for VSMCs, and its expression is an important protective mechanism in regulation of vascular restenosis. PMID:24814101

  3. Efficacy and permanency of ammonia treatment in reducing aflatoxin levels in corn.

    PubMed

    Weng, C Y; Martinez, A J; Park, D L

    1994-01-01

    Naturally contaminated yellow corn containing 12500 ng/g of aflatoxin B1 (AFB1) was ground and blended with non-contaminated corn to obtain various levels of AFB1 (7500, 6300, 400, 354, and 17 ng AFB1/g). All samples were exposed to ammonia treatment under various conditions for 60 min. Treatment variables included ammonia concentration, moisture level of the corn, temperature, and pressure applied. The moisture content of the corn (8%) was adjusted to 12% and 16%, respectively. Four ammonia treatments were conducted for each moisture level: (a) 1.5% and 2.0% gaseous NH3 at 40-45 degrees C and 55 psi; (b) aqueous NH4OH (2.0% as NH3) at 121 degrees C and 17 psi; (c) sequential treatment of (a) and (b); and (d) aqueous NH4OH (2.0% as NH3) at 25 degrees C and 55 psi. For the treatment with 2% gaseous NH3, the reduction in levels of AFB1 in samples containing 12% moisture ranged from 52.7 to 67.7%, while in samples containing 16% moisture, the reduction ranged from 79.4 to 93.1%. Treatment with NH4OH alone at elevated temperatures (b) or following gaseous NH3 treatment (c) resulted in a reduction of the AFB1 content by greater than 99%. Treatment with NH4OH at 25 degrees C (d) showed a lower efficiency in reducing AFB1 levels. The permanency of the process, i.e. reversion of inactivated AFB1 to the parent compound, was studied by exposing the ammonia-treated corn to HCl (pH = 2.0 at 37 degrees C for 2 h) to simulate stomach acidity. The results showed no significant reversion of aflatoxin (reversibility less than 0.05%). These findings suggest that at high temperature aqueous NH4OH or gaseous NH3 can be used effectively to reduce AFB1 in corn. The present study also revealed that the moisture level of the product and holding temperature were the crucial factors that influenced the efficacy of aflatoxin decontamination by ammoniation.

  4. 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.

  5. 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.

  6. Spelling for Writing: Student Activity Book. Level 3.

    ERIC Educational Resources Information Center

    Wright, Reid

    This Student Activity Book is designed to be used with the "Guidebook for Parents and Teachers" of the same series. The Level 3 activity book consists of worksheets intended to help children discover and practice the most impo