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Sample records for activation energy decreased

  1. Possibility of decreasing the activation energy of resistivity of mullite by doping with nickel ion

    NASA Astrophysics Data System (ADS)

    Roy, D.; Das, S.; Nandy, P.

    2012-12-01

    Monophasic mullite samples doped with 0.002 M, 0.02 M, 0.1 M, 0.15 M and 0.2 M of NiCl2 were prepared via sol-gel technique. The prepared gels were dried, grinded, pressed into pellets and sintered at 400 °C, 800 °C, 1000 °C and 1300 °C. The electrical resistivity and activation energy of the composites have been measured and the variation of resistivity with concentration of the nickel ion doping has been investigated. The resistivity decreases with the concentration of nickel ions. X-ray analysis confirms the presence of Ni2+ ions in mullite. The Ni2+ ion, which substitutes Al3+ ion in the octahedral site of mullite structure, can be considered as an efficient factor in reducing the resistivity. The mullite unit cell parameters suggest predominant incorporation of NiCl2 in a glassy phase. The lowest activation energy of resistivity ( E act ) that was achieved is 1.22 eV at 0.02 M.

  2. Male Weasels Decrease Activity and Energy Expenditure in Response to High Ambient Temperatures

    PubMed Central

    Zub, Karol; Fletcher, Quinn E.; Szafrańska, Paulina A.; Konarzewski, Marek

    2013-01-01

    The heat dissipation limit (HDL) hypothesis suggests that the capacity of endotherms to dissipate body heat may impose constraints on their energy expenditure. Specifically, this hypothesis predicts that endotherms should avoid the detrimental consequences of hyperthermia by lowering their energy expenditure and reducing their activity in response to high ambient temperatures (Ta). We used an extensive data set on the daily energy expenditure (DEE, n = 27) and the daily activity time (AT, n = 48) of male weasels (Mustela nivalis) during the spring and summer breeding season to test these predictions. We found that Ta was related in a “hump-shaped” (i.e. convex) manner to AT, DEE, resting metabolic rate (RMR) and metabolic scope (the ratio of DEE to RMR). These results support the HDL hypothesis because in response to warm Tas male weasels reduced their AT, DEE, and RMR. Although the activity and energy expenditure of large endotherms are most likely to be constrained in response to warm Tas because they are less able to dissipate heat, our results suggest that small endotherms may also experience constraints consistent with the HDL hypothesis. PMID:23977336

  3. Decreased material-activation of the complement system using low-energy plasma polymerized poly(vinyl pyrrolidone) coatings.

    PubMed

    Andersen, Thomas E; Palarasah, Yaseelan; Skjødt, Mikkel-Ole; Ogaki, Ryosuke; Benter, Maike; Alei, Mojagan; Kolmos, Hans J; Koch, Claus; Kingshott, Peter

    2011-07-01

    In the current study we investigate the activation of blood complement on medical device silicone rubber and present a plasma polymerized vinyl pyrrolidone (ppVP) coating which strongly decreases surface-activation of the blood complement system. We show that uncoated silicone and polystyrene are both potent activators of the complement system, measured both as activated, deposited C3b and quantifying fluid-phase release of the cleavage fragment C3c. The ppVP coated silicone exhibits approximately 90% reduced complement activation compared to untreated silicone. Quartz crystal microbalance with dissipation (QCM-D) measurements show relatively strong adsorption of blood proteins including native C3 to the ppVP surface, indicating that reduction of complement activation on ppVP is neither a result of low protein adsorption nor lower direct C3-binding, and is therefore possibly a consequence of differences in the adsorbed protein layer composition. The alternative and classical complement pathways are barely detectable on ppVP while the lectin pathway through MBL/ficolin-2 deposition remains active on ppVP suggesting this pathway is responsible for the remaining subtle activation on the ppVP coated surface. The ppVP surface is furthermore characterized physically and chemically using scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR), which indicates preservation of chemical functionality by the applied plasma process. Overall, the ppVP coating shows a potential for increasing complement-compatibility of blood-contacting devices.

  4. Decreased fibrinolytic activity in juvenile chronic arthritis.

    PubMed

    Mussoni, L; Pintucci, G; Romano, G; De Benedetti, F; Massa, M; Martini, A

    1990-12-01

    The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA.

  5. Hypnotic induction decreases anterior default mode activity.

    PubMed

    McGeown, William J; Mazzoni, Giuliana; Venneri, Annalena; Kirsch, Irving

    2009-12-01

    The 'default mode' network refers to cortical areas that are active in the absence of goal-directed activity. In previous studies, decreased activity in the 'default mode' has always been associated with increased activation in task-relevant areas. We show that the induction of hypnosis can reduce anterior default mode activity during rest without increasing activity in other cortical regions. We assessed brain activation patterns of high and low suggestible people while resting in the fMRI scanner and while engaged in visual tasks, in and out of hypnosis. High suggestible participants in hypnosis showed decreased brain activity in the anterior parts of the default mode circuit. In low suggestible people, hypnotic induction produced no detectable changes in these regions, but instead deactivated areas involved in alertness. The findings indicate that hypnotic induction creates a distinctive and unique pattern of brain activation in highly suggestible subjects. PMID:19782614

  6. Decreased fibrinolytic activity in juvenile chronic arthritis.

    PubMed Central

    Mussoni, L; Pintucci, G; Romano, G; De Benedetti, F; Massa, M; Martini, A

    1990-01-01

    The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA. PMID:2125408

  7. A moderate dose of caffeine ingestion does not change energy expenditure but decreases sleep time in physically active males: a double-blind randomized controlled trial.

    PubMed

    Júdice, Pedro B; Magalhães, João P; Santos, Diana A; Matias, Catarina N; Carita, Ana Isabel; Armada-Da-Silva, Paulo A S; Sardinha, Luís B; Silva, Analiza M

    2013-01-01

    Research on the effect of caffeine on energy expenditure (EE), physical activity (PA), and total sleep time (TST) during free-living conditions using objective measures is scarce. We aimed to determine the impact of a moderate dose of caffeine on TST, resting EE (REE), physical activity EE (PAEE), total EE (TEE), and daily time spent in sedentary, light, moderate, and vigorous intensity activities in a 4-day period and the acute effects on heart rate (HR) and EE in physically active males. Using a double-blind crossover trial (ClinicalTrials.gov ID: NCT01477294) with two conditions (4 days each with 3-day washout) randomly ordered as caffeine (5 mg/kg of body mass/day) and placebo (maltodextrin) administered twice per day (2.5 mg/kg), 30 nonsmoker males, low-caffeine users (<100 mg/day), aged 20-39, were followed. Body composition was assessed by dual-energy X-ray absorptiometry. PA was assessed by accelerometry, while a combined HR and movement sensor estimated EE and HR on the second hour after the first administration dose. REE was assessed by indirect calorimetry, and PAEE was calculated as [TEE - (REE + 0.1TEE)]. TST and daily food records were obtained. Repeated measures ANOVA and ANCOVA were used. After a 4-day period, adjusting for fat-free mass, PAEE, and REE, TST was reduced (p = 0.022) under caffeine intake, while no differences were found between conditions for REE, PAEE, TEE, and PA patterns. Also, no acute effects on HR and EE were found between conditions. Though a large individual variability was observed, our findings revealed no acute or long-term effects of caffeine on EE and PA but decreased TST during free-living conditions in healthy males.

  8. Decreased chewing activity during mouth breathing.

    PubMed

    Hsu, H-Y; Yamaguchi, K

    2012-08-01

    This study examined the effect of mouth breathing on the strength and duration of vertical effect on the posterior teeth using related functional parameters during 3 min of gum chewing in 39 nasal breathers. A CO(2) sensor was placed over the mouth to detect expiratory airflow. When no airflow was detected from the mouth throughout the recording period, the subject was considered a nasal breather and enrolled in the study. Electromyographic (EMG) activity was recorded during 3 min of gum chewing. The protocol was repeated with the nostrils occluded. The strength of the vertical effect was obtained as integrated masseter muscle EMG activity, and the duration of vertical effect was also obtained as chewing stroke count, chewing cycle variation and EMG activity duration above baseline. Baseline activity was obtained from the isotonic EMG activity during jaw movement at 1.6 Hz without making tooth contact. The duration represented the percentage of the active period above baseline relative to the 3-min chewing period. Paired t-test and repeated analysis of variance were used to compare variables between nasal and mouth breathing. The integrated EMG activity and the duration of EMG activity above baseline, chewing stroke count and chewing cycle significantly decreased during mouth breathing compared with nasal breathing (P<0.05). Chewing cycle variance during mouth breathing was significantly greater than nasal breathing (P<0.05). Mouth breathing reduces the vertical effect on the posterior teeth, which can affect the vertical position of posterior teeth negatively, leading to malocclusion.

  9. Increased flexibility decreases antifreeze protein activity

    PubMed Central

    Patel, Shruti N; Graether, Steffen P

    2010-01-01

    Antifreeze proteins protect several cold-blooded organisms from subzero environments by preventing death from freezing. The Type I antifreeze protein (AFP) isoform from Pseudopleuronectes americanus, named HPLC6, is a 37-residue protein that is a single α-helix. Mutational analysis of the protein showed that its alanine-rich face is important for binding to and inhibiting the growth of macromolecular ice. Almost all structural studies of HPLC6 involve the use of chemically synthesized protein as it requires a native N-terminal aspartate and an amidated C-terminus for full activity. Here, we examine the role of C-terminal amide and C-terminal arginine side chain in the activity, structure, and dynamics of nonamidated Arg37 HPLC6, nonamidated HPLC6 Ala37, amidated HPLC6 Ala37, and fully native HPLC6 using a recombinant bacterial system. The thermal hysteresis (TH) activities of the nonamidated mutants are 35% lower compared with amidated proteins, but analysis of the NMR data and circular dichroism spectra shows that they are all still α-helical. Relaxation data from the two nonamidated mutants indicate that the C-terminal residues are considerably more flexible than the rest of the protein because of the loss of the amide group, whereas the amidated Ala37 mutant has a C-terminus that is as rigid as the wild-type protein and has high TH activity. We propose that an increase in flexibility of the AFP causes it to lose activity because its dynamic nature prevents it from binding strongly to the ice surface. PMID:20936690

  10. Interactive learning activities for the middle school classroom to promote healthy energy balance and decrease diabetes risk in the HEALTHY primary prevention trial.

    PubMed

    Venditti, Elizabeth M; Giles, Catherine; Firrell, L Suzanne; Zeveloff, Abigail D; Hirst, Kathryn; Marcus, Marsha D

    2014-01-01

    The HEALTHY trial evaluated the effectiveness of a multicomponent intervention program to reduce risk for type 2 diabetes in middle school students. The comprehensive intervention addressed nutrition, physical activity, and behavior in the context of a social marketing-based communications campaign to promote healthy energy balance. One element was a classroom-based program called FLASH (Fun Learning Activities for Student Health). Five FLASH modules were delivered, one per semester. Process evaluation data were collected from teachers at 21 schools and study staff at seven national sites via survey, interview, and in-class observation. Data from the first four modules were evaluated and showed that FLASH was delivered with high fidelity. Sessions that required peer interaction were rated as the most effective in engaging students and promoting knowledge. Study-provided material resources and on-site support were identified as key facilitators. Student misbehavior was viewed as the greatest barrier. Although the high level of support provided by the study is not likely to be replicated in school systems, those developing wellness policies, health curricula, and teacher training programs may benefit from using the evidence-supported, publicly available HEALTHY materials in their efforts to reduce diabetes risk factors in middle school youth.

  11. Exendin-4 Decreases Amphetamine-induced Locomotor Activity

    PubMed Central

    Erreger, Kevin; Davis, Adeola R.; Poe, Amanda M.; Greig, Nigel H.; Stanwood, Gregg D.; Galli, Aurelio

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is released in response to nutrient ingestion and is a regulator of energy metabolism and consummatory behaviors through both peripheral and central mechanisms. The GLP-1 receptor (GLP-1R) is widely distributed in the central nervous system, however little is known about how GLP-1Rs regulate ambulatory behavior. The abused psychostimulant amphetamine (AMPH) promotes behavioral locomotor activity primarily by inducing the release of the neurotransmitter dopamine. Here, we identify the GLP-1R agonist exendin-4 (Ex-4) as a modulator of behavioral activation by AMPH. We report that in rats a single acute administration of Ex-4 decreases both basal locomotor activity as well as AMPH-induced locomotor activity. Ex-4 did not induce behavioral responses reflecting anxiety or aversion. Our findings implicate GLP-1R signaling as a novel modulator of psychostimulant-induced behavior and therefore a potential therapeutic target for psychostimulant abuse. PMID:22465309

  12. Decreased energy levels can cause and sustain obesity.

    PubMed

    Wlodek, Danuta; Gonzales, Michael

    2003-11-01

    Obesity has reached epidemic proportions and has become one of the major health problems in developed countries. Current theories consider obesity a result of overeating and sedentary life style and most efforts to treat or prevent weight gain concentrate on exercise and food intake. This approach does not improve the situation as may be seen from the steep increase in the prevalence of obesity. This encouraged us to reanalyse existing information and look for biochemical basis of obesity. Our approach was to ignore current theories and concentrate on experimental data which are described in scientific journals and are available from several databases. We developed and applied a Knowledge Discovery in Databases procedure to analyse metabolic data. We began with the contradictory information: in obesity, more calories are consumed than used up, suggesting that obese people should have excess energy. On the other side, obese people experience fatigue and decreased physical endurance that indicates diminished energy supply in the body. The result of our work is a chain of metabolic events leading to obesity. The crucial event is the inhibition of the TCA cycle at the step of aconitase. It disturbs energy metabolism and results in ATP deficiency with simultaneous fat accumulation. Further steps in obesity development are the consequences of diminished energy supply: inhibition of beta-oxidation, leptin resistance, increase in appetite and food intake and a decrease in physical activity. Thus, our theory shows that obesity does not have to be caused by overeating and sedentary life-style but may be the result of the "obese" change in metabolism which is forcing people to overeat and save energy to sustain metabolic functions of cells. This "obese" change is caused by environmental factors that activate chronic low-grade inflammatory process in the body linking obesity with the environment of developed countries. PMID:14559057

  13. 43 CFR 4110.3-2 - Decreasing active use.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use,...

  14. 43 CFR 4110.3-2 - Decreasing active use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use,...

  15. 43 CFR 4110.3-2 - Decreasing active use.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use,...

  16. 43 CFR 4110.3-2 - Decreasing active use.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Decreasing active use. 4110.3-2 Section... Qualifications and Preference § 4110.3-2 Decreasing active use. (a) The authorized officer may suspend active use... site inventory, or other acceptable methods, the authorized officer will reduce active use,...

  17. Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL.

    PubMed

    Gowri, M S; Azhar, R K; Kraemer, F B; Reaven, G M; Azhar, S

    2000-09-01

    Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from the creosote bush, has been shown to decrease adipose tissue lipolytic activity both in vivo and in vitro. The present study was initiated to test the hypothesis that the decrease in lipolytic activity by masoprocol resulted from modulation of adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that oral administration of masoprocol to rats with fructose-induced hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P < 0.05), triglyceride (TG; P < 0.001), and insulin (P < 0.05) concentrations. In addition, isoproterenol-induced lipolytic rate and HSL activity were significantly lower (P < 0.001) in adipocytes isolated from masoprocol compared with vehicle-treated rats and was associated with a decrease in HSL protein. Incubation of masoprocol with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol. The results of these in vitro and in vivo experiments suggest that the antilipolytic activity of masoprocol is secondary to its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase activity. As a consequence, masoprocol administration results in lower serum FFA and TG concentrations in hypertriglyceridemic rodents.

  18. Traumatic brain injury decreases AMP-activated protein kinase activity and pharmacological enhancement of its activity improves cognitive outcome.

    PubMed

    Hill, Julia L; Kobori, Nobuhide; Zhao, Jing; Rozas, Natalia S; Hylin, Michael J; Moore, Anthony N; Dash, Pramod K

    2016-10-01

    Prolonged metabolic suppression in the brain is a well-characterized secondary pathology of both experimental and clinical traumatic brain injury (TBI). AMP-activated kinase (AMPK) acts as a cellular energy sensor that, when activated, regulates various metabolic and catabolic pathways to decrease ATP consumption and increase ATP synthesis. As energy availability after TBI is suppressed, we questioned if increasing AMPK activity after TBI would improve cognitive outcome. TBI was delivered using the electromagnetic controlled cortical impact model on male Sprague-Dawley rats (275-300 g) and C57BL/6 mice (20-25 g). AMPK activity within the injured parietal cortex and ipsilateral hippocampus was inferred by western blots using phospho-specific antibodies. The consequences of acute manipulation of AMPK signaling on cognitive function were assessed using the Morris water maze task. We found that AMPK activity is decreased as a result of injury, as indicated by reduced AMPK phosphorylation and corresponding changes in the phosphorylation of its downstream targets: ribosomal protein S6 and Akt Substrate of 160 kDa (AS160). Increasing AMPK activity after injury using the drugs 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide or metformin did not affect spatial learning, but significantly improved spatial memory. Taken together, our results suggest that decreased AMPK activity after TBI may contribute to the cellular energy crisis in the injured brain, and that AMPK activators may have therapeutic utility. Increased phosphorylation of Thr172 activates AMP-activated protein kinase (AMPK) under conditions of low cellular energy availability. This leads to inhibition of energy consuming, while activating energy generating, processes. Hill et al., present data to indicate that TBI decreases Thr172 phosphorylation and that its stimulation by pharmacological agents offers neuroprotection and improves memory. These results suggest that decreased AMPK phosphorylation after

  19. Human NR5A1/SF-1 Mutations Show Decreased Activity on BDNF (Brain-Derived Neurotrophic Factor), an Important Regulator of Energy Balance: Testing Impact of Novel SF-1 Mutations Beyond Steroidogenesis

    PubMed Central

    Malikova, Jana; Camats, Núria; Fernández-Cancio, Mónica; Heath, Karen; González, Isabel; Caimarí, María; del Campo, Miguel; Albisu, Marian; Kolouskova, Stanislava; Audí, Laura; Flück, Christa E.

    2014-01-01

    Context Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. Objective To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. Patients 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. Methods SF-1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). Results Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. Conclusions Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations. PMID:25122490

  20. Selenium bond decreases ON resistance of light-activated switch

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Vitrified amorphous selenium bond decreases the ON resistance of a gallium arsenide-silicon light-activated, low-level switch. The switch is used under a pulse condition to prolong switch life and minimize errors due to heating, devitrification, and overdrawing.

  1. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  2. Why does serotonergic activity drastically decrease during REM sleep?

    PubMed

    Sato, Kohji

    2013-10-01

    Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation.

  3. Berberine Suppresses Adipocyte Differentiation via Decreasing CREB Transcriptional Activity

    PubMed Central

    Deng, Ruyuan; Wang, Ning; Zhang, Yuqing; Wang, Yao; Liu, Yun; Li, Fengying; Wang, Xiao; Zhou, Libin

    2015-01-01

    Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, has been demonstrated to lower blood glucose, blood lipid, and body weight in patients with type 2 diabetes mellitus. The anti-obesity effect of berberine has been attributed to its anti-adipogenic activity. However, the underlying molecular mechanism remains largely unknown. In the present study, we found that berberine significantly suppressed the expressions of CCAAT/enhancer-binding protein (C/EBP)α, peroxisome proliferators-activated receptor γ2 (PPARγ2), and other adipogenic genes in the process of adipogenesis. Berberine decreased cAMP-response element-binding protein (CREB) phosphorylation and C/EBPβ expression at the early stage of 3T3-L1 preadipocyte differentiation. In addition, CREB phosphorylation and C/EBPβ expression induced by 3-isobutyl-1-methylxanthine (IBMX) and forskolin were also attenuated by berberine. The binding activities of cAMP responsive element (CRE) stimulated by IBMX and forskolin were inhibited by berberine. The binding of phosphorylated CREB to the promoter of C/EBPβ was abrogated by berberine after the induction of preadipocyte differentiation. These results suggest that berberine blocks adipogenesis mainly via suppressing CREB activity, which leads to a decrease in C/EBPβ-triggered transcriptional cascades. PMID:25928058

  4. Decreased microglial activation in MS patients treated with glatiramer acetate

    PubMed Central

    Ratchford, John N.; Endres, Christopher J.; Hammoud, Dima A.; Pomper, Martin G.; Shiee, Navid; McGready, John; Pham, Dzung L.; Calabresi, Peter A.

    2012-01-01

    Activated microglia are thought to be an important contributor to tissue damage in multiple sclerosis (MS). The level of microglial activation can be measured non-invasively using [11C]-R-PK11195, a radiopharmaceutical for positron emission tomography (PET). Prior studies have identified abnormalities in the level of [11C]-R-PK11195 uptake in patients with MS, but treatment effects have not been evaluated. Nine previously untreated relapsing-remitting MS patients underwent PET and magnetic resonance imaging (MRI) of the brain at baseline and after one year of treatment with glatiramer acetate. Parametric maps of [11C]-R-PK11195 uptake were obtained for baseline and post-treatment PET scans, and the change in [11C]-R-PK11195 uptake pre- to post-treatment was evaluated across the whole brain. Region of interest analysis was also applied to selected subregions. Whole brain [11C]-R-PK11195 binding potential per unit volume decreased 3.17% (95% CI: −0.74%, −5.53%) between baseline and one year (p = 0.018). A significant decrease was noted in cortical gray matter and cerebral white matter, and a trend towards decreased uptake was seen in the putamen and thalamus. The results are consistent with a reduction in inflammation due to treatment with glatiramer acetate, though a larger controlled study would be required to prove that association. Future research will focus on whether the level of baseline microglial activation predicts future tissue damage in MS and whether [11C]-R-PK11195 uptake in cortical gray matter correlates with cortical lesion load. PMID:22160466

  5. Decrease of fibrinolytic activity in human endothelial cells by arsenite.

    PubMed

    Jiang, Shinn-Jong; Lin, Tsun-Mei; Wu, Hua-Lin; Han, Huai-Song; Shi, Guey-Yueh

    2002-01-01

    Blackfoot disease (BFD) is an endemic peripheral vascular occlusive disease that occurred in the southwest coast of Taiwan. It is believed that arsenic in the drinking water from artesian wells plays an important role in the development of the disease. We have previously shown that BFD patients had significant lower tissue-type plasminogen activator (t-PA) antigen level and higher plasminogen activator inhibitor, Type 1 (PAI-1) antigen level than normal controls. The purpose of this study was to investigate the effects of arsenite on the fibrinolytic and anticoagulant activities of cultured macrovascular and microvascular endothelial cells. Incubation of human microvascular endothelial cells (HMEC-1), but not human umbilical vein endothelial cells (HUVECs), with arsenite caused a decrease of t-PA mRNA level, a rise of both PAI-1 mRNA level and PAI activity. Arsenite could also inhibit the thrombomodulin (TM) mRNA expression and reduce the TM antigen level in HMEC-1. In conclusion, arsenite had a greater effect on HMEC-1 as compared to HUVECs in lowering the fibrinolytic activity and may be responsible for the reduced capacity of fibrinolysis associated with BFD.

  6. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder

    PubMed Central

    Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-01-01

    Objective Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. Methods The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Results Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (p<0.01). Conclusion The findings of the present study suggest that the decrease in prolidase activity may have neuroprotective effects in patients with PTSD. PMID:27482243

  7. Microplastic ingestion decreases energy reserves in marine worms.

    PubMed

    Wright, Stephanie L; Rowe, Darren; Thompson, Richard C; Galloway, Tamara S

    2013-12-01

    The indiscriminate disposal of plastic to the environment is of concern. Microscopic plastic litter (<5 mm diameter; 'microplastic') is increasing in abundance in the marine environment, originating from the fragmentation of plastic items and from industry and personal-care products [1]. On highly impacted beaches, microplastic concentrations (<1mm) can reach 3% by weight, presenting a global conservation issue [2]. Microplastics are a novel substrate for the adherence of hydrophobic contaminants [1], deposition of eggs [3], and colonization by unique bacterial assemblages [4]. Ingestion by indiscriminate deposit-feeders has been reported, yet physical impacts remain understudied [1]. Here, we show that deposit-feeding marine worms maintained in sediments spiked with microscopic unplasticised polyvinylchloride (UPVC) at concentrations overlapping those in the environment had significantly depleted energy reserves by up to 50% (Figure 1). Our results suggest that depleted energy reserves arise from a combination of reduced feeding activity, longer gut residence times of ingested material and inflammation.

  8. Decreased dopamine activity predicts relapse in methamphetamine abusers

    SciTech Connect

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  9. Roles of AQP5/AQP5-G103D in carbamylcholine-induced volume decrease and in reduction of the activation energy for water transport by rat parotid acinar cells.

    PubMed

    Satoh, Keitaro; Seo, Yoshiteru; Matsuo, Shinsuke; Karabasil, Mileva Ratko; Matsuki-Fukushima, Miwako; Nakahari, Takashi; Hosoi, Kazuo

    2012-10-01

    In order to assess the contribution of the water channel aquaporin-5 (AQP5) to water transport by salivary gland acinar cells, we measured the cell volume and activation energy (E (a)) of diffusive water permeability in isolated parotid acinar cells obtained from AQP5-G103D mutant and their wild-type rats. Immunohistochemistry showed that there was no change induced by carbamylcholine (CCh; 1 μM) in the AQP5 detected in the acinar cells in the wild-type rat. Acinar cells from mutant rats, producing low levels of AQP5 in the apical membrane, showed a minimal increase in the AQP5 due to the CCh. In the wild-type rat, CCh caused a transient swelling of the acinus, followed by a rapid agonist-induced cell shrinkage, reaching a plateau at 30 s. In the mutant rat, the acinus did not swell by CCh challenge, and the agonist-induced cell shrinkage was delayed by 8 s, reaching a transient minimum at around 1 min, and recovered spontaneously even though CCh was persistently present. In the unstimulated wild-type acinar cells, E (a) was 3.4 ± 0.6 kcal mol(-1) and showed no detectable change after CCh stimulation. In the unstimulated mutant acinar cells, high E (a) value (5.9 ± 0.1 kcal mol(-1)) was detected and showed a minimal decrease after CCh stimulation (5.0 ± 0.3 kcal mol(-1)). These results suggested that AQP5 was the main pathway for water transport in the acinar cells and that it was responsible for the rapid agonist-induced acinar cell shrinkage and also necessary to keep the acinar cell volume reduced during the steady secretion in the wild-type rat.

  10. Decreased physical activity in Pima Indian compared with Caucasian children.

    PubMed

    Fontvieille, A M; Kriska, A; Ravussin, E

    1993-08-01

    Since reduced physical activity might be a risk factor for body weight gain, we studied the relationship between physical activity and body composition in 43 Pima Indian children (22 male/21 female, mean +/- s.d.: 9.9 +/- 1.1 years) and 42 Caucasian children (21 male/21 female, 9.7 +/- 1.2 years). A list of usual sport leisure activities was established (e.g. bicycling, swimming, basketball) and the subjects were asked how much time they had devoted to each activity over the past week and the last year. Data on time spent playing outside (excluding sport leisure activities for the estimation of physical activity) and watching television/videos were also collected. Pima Indians were taller (143 +/- 9 vs. 137 +/- 8 cm, P < 0.001), heavier (48.6 +/- 15.8 vs. 32.9 +/- 7.8 kg, P < 0.0001) and fatter (39 +/- 16 vs. 24 +/- 7% fat, P < 0.001) than Caucasians. Pima Indian girls showed significantly lower past year and past week sport leisure activity than Caucasian girls (P < 0.01) and spent significantly more time watching television/videos (P < 0.05). Pima boys also showed significantly lower past week sport leisure activity than Caucasian boys (P < 0.05). In Pima Indian boys, past year sport leisure activity correlated negatively (P < 0.05) with body mass index (r = -0.49) and percentage body fat (r = -0.56). However, such correlations were not found in Pima Indian girls, possibly due their very low levels of activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Src activity increases and Yes activity decreases during mitosis of human colon carcinoma cells.

    PubMed Central

    Park, J; Cartwright, C A

    1995-01-01

    Src and Yes protein-tyrosine kinase activities are elevated in malignant and premalignant tumors of the colon. To determine whether Src activity is elevated throughout the human colon carcinoma cell cycle as it is in polyomavirus middle T antigen- or F527 Src-transformed cells, and whether Yes activity, which is lower than that of Src in the carcinoma cells, is regulated differently, we measured their activities in cycling cells. We observed that the activities of both kinases were higher throughout all phases of the HT-29 colon carcinoma cell cycle than in corresponding phases of the fibroblast cycle. In addition, during mitosis of HT-29 cells, Src specific activity increased two- to threefold more, while Yes activity and abundance decreased threefold. The decreased steady-state protein levels of Yes during mitosis appeared to be due to both decreased synthesis and increased degradation of the protein. Inhibition of tyrosine but not serine/threonine phosphatases abolished the mitotic activation of Src. Mitotic Src was phosphorylated at novel serine and threonine sites and dephosphorylated at Tyr-527. Two cellular proteins (p160 and p180) were phosphorylated on tyrosine only during mitosis. Tyrosine phosphorylation of several other proteins decreased during mitosis. Thus, Src in HT-29 colon carcinoma cells, similar to Src complexed to polyomavirus middle T antigen or activated by mutation at Tyr-527, is highly active in all phases of the cell cycle. Moreover, Src activity further increases during mitosis, whereas Yes activity and abundance decrease. Thus, Src and Yes appear to be regulated differently during mitosis of HT-29 colon carcinoma cells. PMID:7739521

  12. Insulin-induced decrease in protein phosphorylation in rat adipocytes not explained by decreased A-kinase activity

    SciTech Connect

    Egan, J.J.; Greenberg, A.S.; Chang, M.K.; Londos, C.

    1987-05-01

    In isolated rat adipocytes, insulin inhibits lipolysis to a greater extent than would be predicted by the decrease in (-/+)cAMP activity ratio of cAMP-dependent protein kinase (A-kinase), from which it was speculated that insulin promotes the dephosphorylation of hormone-sensitive lipase. They have examined the phosphorylation state of cellular proteins under conditions of varying A-kinase activities in the presence and absence of insulin. Protein phosphorylation was determined by SDS-PAGE electrophoresis of extracts from /sup 32/P-loaded cells; glycerol and A-kinase activity ratios were measured in the cytosolic extracts from control, non-radioactive cells. Increased protein phosphorylation in general occurred over the same range of A-kinase activity ratios, 0.1-0.3, associated with increased glycerol release. The insulin-induced decrease in lipolysis was associated with a decrease in the /sup 32/P content of several proteins, an effect not explained by the modest reduction in A-kinase activity by insulin. This effect of insulin on protein phosphorylation was lost as the A-kinase activity ratios exceeded 0.5. The results suggest that insulin promotes the dephosphorylation of those adipocyte proteins which are subject to phosphorylation by A-kinase.

  13. Decrease in gamma-band activity tracks sequence learning

    PubMed Central

    Madhavan, Radhika; Millman, Daniel; Tang, Hanlin; Crone, Nathan E.; Lenz, Fredrick A.; Tierney, Travis S.; Madsen, Joseph R.; Kreiman, Gabriel; Anderson, William S.

    2015-01-01

    Learning novel sequences constitutes an example of declarative memory formation, involving conscious recall of temporal events. Performance in sequence learning tasks improves with repetition and involves forming temporal associations over scales of seconds to minutes. To further understand the neural circuits underlying declarative sequence learning over trials, we tracked changes in intracranial field potentials (IFPs) recorded from 1142 electrodes implanted throughout temporal and frontal cortical areas in 14 human subjects, while they learned the temporal-order of multiple sequences of images over trials through repeated recall. We observed an increase in power in the gamma frequency band (30–100 Hz) in the recall phase, particularly in areas within the temporal lobe including the parahippocampal gyrus. The degree of this gamma power enhancement decreased over trials with improved sequence recall. Modulation of gamma power was directly correlated with the improvement in recall performance. When presenting new sequences, gamma power was reset to high values and decreased again after learning. These observations suggest that signals in the gamma frequency band may play a more prominent role during the early steps of the learning process rather than during the maintenance of memory traces. PMID:25653598

  14. Stereotypic wheel running decreases cortical activity in mice

    PubMed Central

    Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

    2016-01-01

    Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

  15. Experimental evaluation of decrease in bacterial activity due to cell death and activity decay in activated sludge.

    PubMed

    Hao, Xiaodi; Wang, Qilin; Zhang, Xiangping; Cao, Yali; van Mark Loosdrecht, C M

    2009-08-01

    Decrease in bacterial activity (cell decay) in activated sludge can be attributed to cell death (reduction in the amount of active bacteria) and activity decay (reduction in the specific activity of active bacteria). The aim of this study was to experimentally differentiate between cell death and activity decay as a source of decrease in microbial activity. By means of measuring maximal oxygen uptake rates, verifying membrane integrity by live/dead staining and verifying presence of 16S rRNA with fluorescence in-situ hybridization, the decay rates and the death rates of ammonium oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and ordinary heterotrophic organisms (OHOs) were determined respectively in a nitrifying sequencing batch reactor (SBR) and a heterotrophic SBR. The experiments revealed that in the nitrifying system activity decay contributed 47% and 82% to the decreased activities of AOB and NOB and that cell death was responsible for 53% and 18% of decreases in their respective activities. In the heterotrophic system, activity decay took a share of 78% in the decreased activity of OHOs, and cell death was only responsible for 22% of decrease in their activity. The difference between the importance of cell death on the decreased activities of AOB and OHOs might be caused by the mechanisms of substrate storage and/or cryptic growth/death-regeneration of OHOs. The different nutrient sources for AOB and NOB might be the reason for a relatively smaller fraction of cell death in NOB.

  16. Capturing coefficient increase and energy spread decrease in LPWA

    NASA Astrophysics Data System (ADS)

    Polozov, S. M.; Rashchikov, V. I.

    2016-09-01

    The acceleration of electrons in laser plasma channels is one of the contemporary ideas on energy frontier of accelerators. Many simulations and experimental studies are now provided. But two main laser plasma acceleration problems are not solved until now: low fraction of particles is capturing into acceleration and accelerated electrons have very broad band. Especial techniques should be proposed to preserve such negative effects. New results of beam dynamics simulations in laser plasma channel having pre-bunching stage are discussed in article. Results are obtained for two pre-bunching techniques which are analogous to waveguide and klystron type buncher used in RF accelerators

  17. Endothelial cell phagocytosis of senescent neutrophils decreases procoagulant activity.

    PubMed

    Gao, Chunyan; Xie, Rui; Li, Wen; Zhou, Jin; Liu, Shuchuan; Cao, Fenglin; Liu, Yue; Ma, Ruishuang; Si, Yu; Liu, Yan; Bi, Yayan; Gilbert, Gary E; Shi, Jialan

    2013-06-01

    Abundant senescent neutrophils traverse the vascular compartment and may contribute to pathologic conditions. For example, they become procoagulant when undergoing apoptosis and may contribute to thrombosis or inflammation. Our previous studies demonstrated a dominant clearance pathway in which the neutrophils can be phagocytosed by liver macrophages. The aim of this study was to explore an alternate pathway of neutrophil clearance by endothelial cells. Phagocytosis of the neutrophils by endothelial cells was performed using various experimental approaches includingflow cytometry, confocal microscopy and electron microscopy assays in vitro and in vivo. Procoagulant activity of cultured neutrophils was evaluated by coagulation time, factor Xase and prothrombinase assays. Lactadherin functioned as a novel probe for the detection of phosphatidylserine on apoptotic cells, an opsonin (bridge) between apoptotic cell and phagocyte for promoting phagocytosis, and an efficient anticoagulant for inhibition of factor Xase and thrombin formation. When cultured, purified human neutrophils spontaneously entered apoptosis and developed procoagulant activity that was directly related to the degree of phosphatidylserine exposure. Co-culture of aged neutrophils and endothelial cells resulted in phagocytosis of the neutrophils and prolonged coagulation time. Lactadherin diminished the procoagulant activity and increased the rate of neutrophil clearance. In vivo, neutrophils were sequestered by endothelial cells after blockade of Kupffer cells, a process that was dependent upon both phosphatidylserine exposure and P-selectin expression. Thus, the ability of endothelial cells to clear senescent neutrophils may limit the procoagulant and/or inflammatory impact of these cells.

  18. Decrease in T Cell Activation and Calcium Flux during Clinorotation

    NASA Technical Reports Server (NTRS)

    Sams, Clarence; Holtzclaw, J. David

    2006-01-01

    We investigated the effect of altered gravitational environments on T cell activation. We isolated human, naive T cells (CD3+CD14-CD19-CD16-CD56-CD25-CD69-CD45RA-) following IRB approved protocols. These purified T cells were then incubated with 6 mm polystyrene beads coated with OKT3 (Ortho Biotech, Raritan, NJ) and antiCD28 (Becton Dickinson (BD), San Jose, CA) at 37 C for 24 hours. Antibodies were at a 1:1 ratio and the bead-to-cell ratio was 2:1. Four incubation conditions existed: 1) static or "1g"; 2) centrifugation at 10 relative centrifugal force (RCF) or "10g"; 3) clinorotation at 25 RPM (functional weightlessness or "0g"); and 4) clinorotation at 80 RPM ("1g" plus net shear force approx.30 dynes/sq cm). Following incubation, T cells were stained for CD25 expression (BD) and intracellular calcium (ratio of Fluo4 to Fura Red, Molecular Probes, Eugene, OR) and analyzed by flow cytometry (Coulter EPICS XL, Miami, FL). Results: Static or "1g" T cells had the highest level of CD25 expression and intracellular calcium. T cells centrifuged at 10 RCF ("10g") had lower CD25 expression and calcium levels compared to the static control. However, cells centrifuged at 10 RCF had higher CD25 expression and calcium levels than those exposed to 24 RPM clinorotation ("0g"). T cells exposed to 24 RPM clinorotation had lower CD25 expression, but the approximately the same calcium levels than T cells exposed to 80 RPM clinorotation. These data suggest that stress-activated calcium channel exist in T cells and may play a role during T cell activation.

  19. Energy, industry and nitrogen: strategies for decreasing reactive nitrogen emissions.

    PubMed

    Moomaw, William R

    2002-03-01

    Nitrogen oxides are released during atmospheric combustion of fossil fuels and biomass, and during the production of certain chemicals and products. They can react with natural or man-made volatile organic compounds to produce smog, or else can be further oxidized to produce particulate haze, or acid rain that can eutrophy land and water. The reactive nitrogen that begins in the energy sector thus cascades through the atmosphere, the hydrosphere and soils before being eventually partially denitrifed to the global warming and stratospheric ozone-depleting gas nitrous oxide or molecular nitrogen. This paper will suggest how an economic analysis of the nitrogen cycle can identify the most cost-effective places to intervene. Nitrogen oxides released during fossil-fuel combustion in vehicles, power plants and heating boilers can either be controlled by add-on emission control technology, or can be eliminated by many of the same technical options that lead to carbon dioxide reduction. These integrated strategies also address sustainability, economic development and national security issues. Similarly in industrial production, it is more effective to focus on redesigning industrial processes rather than on nitrogen oxide pollution elimination from the current system. This paper will suggest which strategies might be utilized to address multiple benefits rather than focusing on single pollutants. PMID:12078008

  20. Decreasing geothermal energy conversion costs with advanced materials

    SciTech Connect

    Kukacka, L.E.

    1988-03-01

    If the Geothermal Technology Division (GTD) is to meet its programmatic objectives in hydrothermal fluid production and energy conversion, it is essential that new materials of construction be available. Level III Program Objectives include (1) reducing the costs associated with lost circulation episodes by 30% by 1992, (2) reducing the costs of deep wells and directionally dried wells by 10% by 1992, (3) reducing well-cementing problems for typical hydrothermal wells by 20% by 1991, and (4) the development of a corrosion-resistant and low-fouling heat exchanger tube material costing no more than three times the cost of carbon steel tubes by 1991. The Brookhaven National Laboratory (BNL) materials program is focused on meeting these objectives. Currently, work is in progress on (1) high temperature chemical systems for lost circulation control, (2) advanced high temperature (300/sup 0/C), lightweight (approx. 1.1 g/cc), CO/sub 2/-resistant well cementing materials, (3) thermally conductive composites for heat exchanger tubing, and (4) ultra high temperature (600/sup 0/C) cements for magma wells. In addition, high temperature elastomer technology developed earlier in the program is being transferred for use in the Geothermal Drilling Organization programs on drill pipe protectors, rotating head seals, and blow-out preventors. Recent accomplishments and the current status of work in each subtask are summarized in the paper.

  1. Energy, industry and nitrogen: strategies for decreasing reactive nitrogen emissions.

    PubMed

    Moomaw, William R

    2002-03-01

    Nitrogen oxides are released during atmospheric combustion of fossil fuels and biomass, and during the production of certain chemicals and products. They can react with natural or man-made volatile organic compounds to produce smog, or else can be further oxidized to produce particulate haze, or acid rain that can eutrophy land and water. The reactive nitrogen that begins in the energy sector thus cascades through the atmosphere, the hydrosphere and soils before being eventually partially denitrifed to the global warming and stratospheric ozone-depleting gas nitrous oxide or molecular nitrogen. This paper will suggest how an economic analysis of the nitrogen cycle can identify the most cost-effective places to intervene. Nitrogen oxides released during fossil-fuel combustion in vehicles, power plants and heating boilers can either be controlled by add-on emission control technology, or can be eliminated by many of the same technical options that lead to carbon dioxide reduction. These integrated strategies also address sustainability, economic development and national security issues. Similarly in industrial production, it is more effective to focus on redesigning industrial processes rather than on nitrogen oxide pollution elimination from the current system. This paper will suggest which strategies might be utilized to address multiple benefits rather than focusing on single pollutants.

  2. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  3. Serum leptin, energy budget, and thermogenesis in striped hamsters exposed to consecutive decreases in ambient temperatures.

    PubMed

    Zhao, Zhi-Jun

    2011-01-01

    Leptin has been found to be a direct participant in the regulation of both energy intake and energy expenditure in small mammals showing seasonal declines in body mass (M(b)) and fat mass, but its roles in an animal exhibiting seasonally increased thermogenesis and unchanged M(b) remain unclear. Serum leptin levels, energy budget, and thermogenesis were measured in striped hamsters exposed to consecutive decreases in ambient temperatures ranging from 23° to -23°C. Cold-exposed hamsters had significant increases in gross energy intake (GEI), the rate of basal metabolism, nonshivering thermogenesis, and activity of cytochrome c oxidase (COX) in brown adipose tissue (BAT), compared with control hamsters, indicating a cold-induced elevation of thermogenesis. Body mass and fat content were decreased in cold-exposed animals, and serum leptin levels were increased in hamsters exposed to temperatures of -8°C and below in inverse proportion to body fat content. Serum leptin levels were positively correlated with GEI and BAT COX activity in cold-exposed hamsters, but no such relationships were observed in control animals. These findings suggest that cold-exposed hamsters increase food consumption to meet the energy requirements for increased BAT thermogenesis. The increases in serum leptin levels are likely involved in increased thermogenesis in hamsters under cold stress. Cold-exposed hamsters may become leptin resistant, which is associated with impaired regulation of food intake. This new natural model of leptin resistance may also provide insight into the dynamic long-term control of energy homeostasis for animals that do not exhibit seasonal decline in M(b).

  4. Science Activities in Energy: Electrical Energy.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 16 activities relating to electrical energy. Activities are simple, concrete experiments for fourth, fifth and sixth grades which illustrate principles and problems relating to energy. Each activity is outlined in a single card which is introduced by a question. A teacher's…

  5. Science Activities in Energy: Solar Energy.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 12 activities relating to solar energy. Activities are simple, concrete experiments for fourth, fifth, and sixth grades, which illustrate principles and problems relating to energy. Each activity is outlined on a single card which is introduced by a question. A teacher's supplement…

  6. Science Activities in Energy: Chemical Energy.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 15 activities relating to chemical energy. Activities are simple, concrete experiments for fourth, fifth and sixth grades which illustrate principles and problems relating to energy. Each activity is outlined on a single card which is introduced by a question. A teacher's…

  7. Effects of decreased muscle activity on developing axial musculature in nicb107 mutant zebrafish (Danio rerio).

    PubMed

    van der Meulen, T; Schipper, H; van Leeuwen, J L; Kranenbarg, S

    2005-10-01

    The present paper discusses the effects of decreased muscle activity (DMA) on embryonic development in the zebrafish. Wild-type zebrafish embryos become mobile around 18 h post-fertilisation, long before the axial musculature is fully differentiated. As a model for DMA, the nic(b107) mutant was used. In nic(b107) mutant embryos, muscle fibres are mechanically intact and able to contract, but neuronal signalling is defective and the fibres are not activated, rendering the embryos immobile. Despite the immobility, distinguished slow and fast muscle fibres developed at the correct location in the axial muscles, helical muscle fibre arrangements were detected and sarcomere architecture was generated. However, in nic(b107) mutant embryos the notochord is flatter and the cross-sectional body shape more rounded, also affecting muscle fibre orientation. The stacking of sarcomeres and myofibril arrangement show a less regular pattern. Finally, expression levels of several genes were changed. Together, these changes in expression indicate that muscle growth is not impeded and energy metabolism is not changed by the decrease in muscle activity but that the composition of muscle is altered. In addition, skin stiffness is affected. In conclusion, the lack of muscle fibre activity did not prevent the basal muscle components developing but influenced further organisation and differentiation of these components. PMID:16169945

  8. Silencing of Doublecortin-Like (DCL) Results in Decreased Mitochondrial Activity and Delayed Neuroblastoma Tumor Growth

    PubMed Central

    Verissimo, Carla S.; Elands, Rachel; Cheng, Sou; Saaltink, Dirk-Jan; ter Horst, Judith P.; Alme, Maria N.; Pont, Chantal; van de Water, Bob; Håvik, Bjarte; Fitzsimons, Carlos P.; Vreugdenhil, Erno

    2013-01-01

    Doublecortin-like (DCL) is a microtubule-binding protein crucial for neuroblastoma (NB) cell proliferation. We have investigated whether the anti-proliferative effect of DCL knockdown is linked to reduced mitochondrial activity. We found a delay in tumor development after DCL knockdown in vivo in doxycycline-inducible NB tumor xenografts. To understand the mechanisms underlying this tumor growth retardation we performed a series of in vitro experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results in decreased expression of genes involved in oxidative phosphorylation. Moreover, DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We identified the C-terminal Serine/Proline-rich domain and the second microtubule-binding area as crucial DCL domains for the regulation of cytochrome c oxidase activity and ATP synthesis. Furthermore, DCL knockdown causes a significant reduction in the proliferation rate of NB cells under an energetic challenge induced by low glucose availability. Together with our previous studies, our results corroborate DCL as a key player in NB tumor growth in which DCL controls not only mitotic spindle formation and the stabilization of the microtubule cytoskeleton, but also regulates mitochondrial activity and energy availability, which makes DCL a promising molecular target for NB therapy. PMID:24086625

  9. Aerobic training in rats increases skeletal muscle sphingomyelinase and serine palmitoyltransferase activity, while decreasing ceramidase activity.

    PubMed

    Błachnio-Zabielska, Agnieszka; Zabielski, Piotr; Baranowski, Marcin; Gorski, Jan

    2011-03-01

    Sphingolipids are important components of cell membranes that may also serve as cell signaling molecules; ceramide plays a central role in sphingolipid metabolism. The aim of this study was to examine the effect of 5 weeks of aerobic training on key enzymes and intermediates of ceramide metabolism in skeletal muscles. The experiments were carried out on rats divided into two groups: (1) sedentary and (2) trained for 5 weeks (on a treadmill). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and aSMase), neutral and alkaline ceramidases (nCDase and alCDase) and the content of sphingolipids was determined in three types of skeletal muscle. We also measured the fasting plasma insulin and glucose concentration for calculating HOMA-IR (homeostasis model assessment) for estimating insulin resistance. We found that the activities of aSMase and SPT increase in muscle in the trained group. These changes were followed by elevation in the content of sphinganine. The activities of both isoforms of ceramidase were reduced in muscle in the trained group. Although the activities of SPT and SMases increased and the activity of CDases decreased, the ceramide content did not change in any of the studied muscle. Although ceramide level did not change, we noticed increased insulin sensitivity in trained animals. It is concluded that training affects the activity of key enzymes of ceramide metabolism but also activates other metabolic pathways which affect ceramide metabolism in skeletal muscles.

  10. Changing Conceptions of Activation Energy.

    ERIC Educational Resources Information Center

    Pacey, Philip D.

    1981-01-01

    Provides background material which relates to the concept of activation energy, fundamental in the study of chemical kinetics. Compares the related concepts of the Arrhenius activation energy, the activation energy at absolute zero, the enthalpy of activation, and the threshold energy. (CS)

  11. An Asp7Gly substitution in PPARG is associated with decreased transcriptional activation activity.

    PubMed

    Hua, Liushuai; Wang, Jing; Li, Mingxun; Sun, Xiaomei; Zhang, Liangzhi; Lei, Chuzhao; Lan, Xianyong; Fang, Xingtang; Zhao, Xin; Chen, Hong

    2014-01-01

    As the master regulator of adipogenesis, peroxisome proliferator-activated receptor gamma (PPARG) is required for the accumulation of adipose tissue and hence contributes to obesity. A previous study showed that the substitution of +20A>G in PPARG changed the 7(th) amino acid from Asp to Gly, creating a mutant referred to as PPARG Asp7Gly. In this study, association analysis indicated that PPARG Asp7Gly was associated with lower body height, body weight and heart girth in cattle (P<0.05). Overexpression of PPARG in NIH3T3-L1 cells showed that the Asp7Gly substitution may cause a decrease in its adipogenic ability and the mRNA levels of CIDEC (cell death-inducing DFFA-like effector c) and aP2, which are all transcriptionally activated by PPARG during adipocyte differentiation. A dual-luciferase reporter assay was used to analyze the promoter activity of CIDEC. The results confirmed that the mutant PPARG exhibited weaker transcriptional activation activity than the wild type (P<0.05). These findings likely explain the associations between the Asp7Gly substitution and the body measurements. Additionally, the Asp7Gly mutation may be used in molecular marker assisted selection (MAS) of cattle breeding in the future. PMID:24466299

  12. Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity.

    PubMed

    Fujikawa, Teppei; Fujita, Ryo; Iwaki, Yoko; Matsumura, Shigenobu; Fushiki, Tohru; Inoue, Kazuo

    2010-10-01

    We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.

  13. Why even active people get fatter--the asymmetric effects ofincreasing and decreasing exercise

    SciTech Connect

    Williams, Paul T.

    2006-01-06

    Background: Public health policies for preventing obesityneed guidelines for active individuals who are at risk due to exerciserecidivism. Methods: Changes in adiposity were compared to the runningdistances at baseline and follow-up in men and women whose reportedexercise increased (N=4,632 and 1,953, respectively) or decreased (17,280and 5,970, respectively) during 7.7 years of follow-up. Results: PerDelta km/wk, decreases in running distance caused over four-fold greaterweight gain between 0-8 km/wk (slope+-SE, males: -0.068+ -0.005 kg/m2,females: -0.080+-0.01 kg/m2) than between 32-48 km/wk (-0.017+-0.002 and-0.010+-0.005 kg/m2, respectively). In contrast, increases in runningdistance produced the smallest weight losses between 0-8 km/wk andstatistically significant weight loss only above 16 km/wk in males and 32km/wk in females. Above 32 km/wk (30 kcal/kg) in men and 16 km/wk (15kcal/kg) in women, weight loss from increasing exercise was equal to orgreater than weight gained with decreasing exercise, otherwise weightgain exceeded weight loss. Substantial weight gain occurred in runnerswho quit running, which would be mostly retained with resumed activity.Conclusion: Public health recommendations should warn against the risksof irreversible weight gain with exercise cessation. Weight gained due toreductions in exercise below 30 kcal/kg in men and 15 kcal/kg in womenmay not be reversed by resuming prior activity. Current IOM guidelines(i.e., maintain total energy expenditure at 160 percent of basal) agreewith the men s exercise threshold for symmetric weight change withchanging exercise levels.

  14. Activities Handbook for Energy Education.

    ERIC Educational Resources Information Center

    DeVito, Alfred; Krockover, Gerald H.

    The purpose of this handbook is to present information about energy and to translate this information into learning activities for children. Chapter 1, "Energy: A Delicate Dilemma," presents activities intended to provide an introduction to energy and energy usage. Chapter 2, "What are the Sources of Energy?" provides background information and…

  15. Energy Adventure Center. Activity Book.

    ERIC Educational Resources Information Center

    Carlton, Linda L.

    Energy activities are provided in this student activity book. They include: (1) an energy walk; (2) forms of energy in the home; (3) energy conversion; (4) constructing a solar hot dog cooker (with instructions for drawing a parabola); (5) interviewing senior citizens to learn about energy use in the past; (6) packaging materials; (7) insulation;…

  16. Science Activities in Energy: Conservation.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 14 activities relating to energy conservation. Activities are simple, concrete experiments for fourth, fifth and sixth grades, which illustrate principles and problems relating to energy. Each activity is outlined on a simple card which is introduced by a question. A teacher's…

  17. Science Activities in Energy: Wind Energy.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Included in this science activities energy package are 12 activities related to wind energy for elementary students. Each activity is outlined on a single card and is introduced by a question. Topics include: (1) At what time of day is there enough wind to make electricity where you live?; (2) Where is the windiest spot on your schoolground?; and…

  18. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

    PubMed

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-04-01

    Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  19. Decreased aperture surface energy enhances electrical, mechanical, and temporal stability of suspended lipid membranes

    PubMed Central

    Bright, Leonard K.; Baker, Christopher A.; Agasid, Mark T.; Ma, Lin; Aspinwall, Craig A.

    2013-01-01

    The development of next-generation transmembrane protein-based biosensors relies heavily on the use of black lipid membranes (BLMs); however, electrical, mechanical, and temporal instability of BLMs pose a limiting challenge to biosensor development. In this work, micron-sized glass apertures were modified with silanes of different chain length and fluorine composition, including 3-cyanopropyldimethychlorosilane (CPDCS), ethyldimethylchlorosilane (EDCS), n-octyldimethylchlorosilane (ODCS), (tridecafluoro 1, 1, 2, 2-tetrahydrooctyl)dimethylchlorosilane (PFDCS) or (heptadecafluoro-1,1,2,2-tetrahydrodecyl)dimethylchlorosilane (PFDDCS) to explore the effect of substrate surface energy on BLM stability. Low energy silane-modified surfaces promoted enhanced lipid-substrate interactions that facilitate the formation of low-leakage, stable BLMs. The surface energies of silane-modified substrates were 30 ± 3, 16 ± 1, 14 ± 2, 11 ± 1 and 7.1 ± 2 mJ m−2 for CDCS, EDCS, ODCS, PFDCS and PFDDCS, respectively. Decreased surface energy directly correlated to improved electrical, mechanical, and temporal BLM stability. Amphiphobic perfluorinated surface modifiers yielded superior performance compared to traditional hydrocarbon modifiers in terms of stability and BLM formation, with only marginal effects on BLM membrane permeability. Leakage currents obtained for PFDCS and PFDDCS BLMs were elevated only 10-30%, though PFDDCS modification yielded > 5-fold increase in electrical stability as indicated by breakdown voltage (> 2000 mV vs. 418 ± 73 mV), and > 25-fold increase in mechanical stability as indicated by air-water transfers (> 50 vs. 2 ± 0.2) when compared to previously reported CPDCS modification. Importantly, the dramatically improved membrane stabilities were achieved with no deleterious effects on reconstituted ion channel function as evidenced by α-hemolysin activity. Thus, this approach provides a simple, low cost and broadly applicable alternative for BLM

  20. Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism.

    PubMed

    Gleerup, G; Winther, K

    1991-02-01

    Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity.

  1. Expression of uncoupling protein 1 in skeletal muscle decreases muscle energy efficiency and affects thermoregulation and substrate oxidation.

    PubMed

    Klaus, Susanne; Rudolph, Bettina; Dohrmann, Cord; Wehr, Roland

    2005-04-14

    Skeletal muscle uncoupling by ectopic expression of mitochondrial uncoupling protein 1 (UCP1) has been shown to result in a lean phenotype in mice characterized by increased energy expenditure (EE), resistance to diet-induced obesity, and improved glucose tolerance. Here, we investigated in detail the effect of ectopic UCP1 expression in skeletal muscle on thermoregulation and energy homeostasis in HSA-mUCP1 transgenic mice. Thermoneutrality was determined to be approximately 30 degrees C for both wild-type (WT) and transgenic mice. EE, body temperature (Tb), activity, and respiratory quotient (RQ) were then measured over 24 h at ambient temperatures (Ta) of 30, 22, and 5 degrees C. HSA-mUCP1 transgenic mice showed increased activity-related EE and heat loss but similar basal metabolic rate compared with WT. Tb at resting periods was progressively decreased with declining Ta in HSA-mUCP1 transgenic mice but not in WT. Compared with WT littermates, the transgenic HSA-mUCP1 mice displayed increased RQ levels during night time, indicative of increased overall glucose oxidation, and failed to decrease their RQ levels with declining Ta. Thus increased EE caused by skeletal muscle uncoupling is clearly due to a decreased muscle energy efficiency during activity combined with increased glucose oxidation and a compromised thermoregulation associated with increased overall heat loss. At Tas below thermoneutrality, this puts increasing energy demands on the animals, whereas at thermoneutrality most differences in energy metabolism are not apparent any more.

  2. Fruits and Vegetables Displace, But Do Not Decrease, Total Energy in School Lunches

    PubMed Central

    Schoeller, Dale A.

    2014-01-01

    Abstract Background: The high overweight and obesity prevalence among US children is a well-established public health concern. Diet is known to play a causal role in obesity. Increasing fruit and vegetable (FV) consumption to recommended levels is proposed to help reduce obesity, because their bulk and low energy density are believed to reduce energy-dense food consumption (volume displacement hypothesis). This study tests this hypothesis at the lunch meal among upper-elementary students participating in a Farm to School (F2S) program. Methods: Digital photographs of students' school lunch trays were visually analyzed to identify the food items and amounts that were present and consumed before and after the meal. Using the USDA Nutrient Database, total and FV-only energy were calculated for each tray. Analysis of total- and non-FV energy intake was performed according to (1) levels of FV energy intake, (2) FV energy density, and (3) previous years of Farm to School programming. Results: Higher intake of FV energy displaced non-FV energy, but total energy did not decrease across FV energy intake groups. High-FV-energy-density trays showed lower non-FV energy intake than low-FV-energy-density trays (470±179 vs. 534±219 kcal; p<0.0001). Trays from schools with more previous years of F2S programming decreased total and non-FV energy intake from school lunches (p for trend<0.0001, both). Conclusions: Increased FV consumption reduces non-FV energy intake, but does not reduce total energy intake. Therefore, this study does not support the volume displacement hypothesis and suggests calorie displacement instead. PMID:24988122

  3. Science Activities in Energy: Solar Energy II.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Included in this science activities energy package are 14 activities related to solar energy for secondary students. Each activity is outlined on a single card and is introduced by a question such as: (1) how much solar heat comes from the sun? or (2) how many times do you have to run water through a flat-plate collector to get a 10 degree rise in…

  4. Energy budget during four successive bouts of lactation in striped hamsters exposed to decreases in ambient temperature.

    PubMed

    Zhao, Zhi-Jun

    2011-10-01

    A prediction of the seasonal investment hypothesis is that overall energy investment needs to be greater for young being produced at colder temperatures. Then, that energy cost is lower as temperature becomes warmer. To evaluate this assumption, I performed a series of measures of food intake and reproductive output throughout four successive bouts of lactation in striped hamsters (Cricetulus barabensis) exposed to a constant warm temperature (Warm, 21°C) or exposed to consecutive decreases in ambient temperatures from warm to cold (Warm-Cold, 30-0°C). Warm hamsters showed similar asymptotic food intake, litter size and mass over the course of four successive bouts of lactation. Warm-Cold females consumed more food, but raised lighter litters during the third bout than first bout of lactation. Ambient temperatures had significant effects on energy budget and reproductive output, by which resting metabolic rate, nonshivering thermogenesis and activity of cytochrome c oxidase (EC 1.9.3.1) of brown adipose tissue were increased, but reproductive output was decreased with declines of temperatures. These findings suggest that a trade-off occurs between different components of energy expenditure during the successive course of four bouts of lactation. Seasonal hamsters decrease their reproductive output, but increase the energy spent on thermogenesis as the ambient temperature becomes colder. It may also indicate that temperature has a direct effect on metabolism, leading to an increase in overall energy expenditure at lower temperatures.

  5. Activation of membrane-associated estrogen receptors decreases food and water intake in ovariectomized rats.

    PubMed

    Santollo, Jessica; Marshall, Anikó; Daniels, Derek

    2013-01-01

    Estradiol (E2) decreases food and water intake in a variety of species, including rats. Available evidence suggests that this is mediated by genomic mechanisms that are most often attributed to nuclear estrogen receptors. More recent studies indicate that membrane-associated estrogen receptors (mERs) also can influence gene expression through the activation of transcription factors, yet it is unclear whether mERs are involved in mediating the hypophagic and antidipsetic effects of E2. In the present experiments, we injected E2 or a membrane-impermeable form of E2 (E2-BSA) into the lateral cerebral ventricle of ovariectomized female rats and evaluated the effect on 23 h food and water intake. First, we found that higher doses of E2 were necessary to reduce water intake than were sufficient to reduce food intake. Analysis of drinking microstructure revealed that the decrease in water intake after E2 treatment was mediated by both a decrease in burst number and burst size. Next, the activation of mERs with E2-BSA decreased both overnight food and water intake and analysis of drinking microstructure indicated that the decreased water intake resulted from a decrease in burst number. Finally, E2-BSA did not condition a taste aversion, suggesting that the inhibitory effects on food and water intake were not secondary to malaise. Together these findings suggest that activation of mERs is sufficient to decrease food and water intake in female rats.

  6. Phosphorylation by protein kinase C decreases catalytic activity of avian phospholipase C-beta.

    PubMed Central

    Filtz, T M; Cunningham, M L; Stanig, K J; Paterson, A; Harden, T K

    1999-01-01

    The potential role of protein kinase C (PKC)-promoted phosphorylation has been examined in the G-protein-regulated inositol lipid signalling pathway. Incubation of [32P]Pi-labelled turkey erythrocytes with either the P2Y1 receptor agonist 2-methylthioadenosine triphosphate (2MeSATP) or with PMA resulted in a marked increase in incorporation of 32P into the G-protein-activated phospholipase C PLC-betaT. Purified PLC-betaT also was phosphorylated by PKC in vitro to a stoichiometry (mean+/-S. E.M.) of 1.06+/-0.2 mol of phosphate/mol of PLC-betaT. Phosphorylation by PKC was isoenzyme-specific because, under identical conditions, mammalian PLC-beta2 also was phosphorylated to a stoichiometry near unity, whereas mammalian PLC-beta1 was not phosphorylated by PKC. The effects of PKC-promoted phosphorylation on enzyme activity were assessed by reconstituting purified PLC-betaT with turkey erythrocyte membranes devoid of endogenous PLC activity. Phosphorylation resulted in a decrease in basal activity, AlF4(-)-stimulated activity, and activity stimulated by 2MeSATP plus guanosine 5'-[gamma-thio]triphosphate in the reconstituted membranes. The decreases in enzyme activities were proportional to the extent of PKC-promoted phosphorylation. Catalytic activity assessed by using mixed detergent/phospholipid micelles also was decreased by up to 60% by phosphorylation. The effect of phosphorylation on Gqalpha-stimulated PLC-betaT in reconstitution experiments with purified proteins was not greater than that observed on basal activity alone. Taken together, these results illustrate that PKC phosphorylates PLC-betaT in vivo and to a physiologically relevant stoichiometry in vitro. Phosphorylation is accompanied by a concomitant loss of enzyme activity, reflected as a decrease in overall catalytic activity rather than as a specific modification of G-protein-regulated activity. PMID:10024500

  7. Correlations Decrease with Propagation of Spiking Activity in the Mouse Barrel Cortex

    PubMed Central

    Ranganathan, Gayathri Nattar; Koester, Helmut Joachim

    2011-01-01

    Propagation of suprathreshold spiking activity through neuronal populations is important for the function of the central nervous system. Neural correlations have an impact on cortical function particularly on the signaling of information and propagation of spiking activity. Therefore we measured the change in correlations as suprathreshold spiking activity propagated between recurrent neuronal networks of the mammalian cerebral cortex. Using optical methods we recorded spiking activity from large samples of neurons from two neural populations simultaneously. The results indicate that correlations decreased as spiking activity propagated from layer 4 to layer 2/3 in the rodent barrel cortex. PMID:21629764

  8. Effects of decreased dietary roughage concentration on energy metabolism and nutrient balance in finishing beef cattle.

    PubMed

    Hales, K E; Brown-Brandl, T M; Freetly, H C

    2014-01-01

    The optimal roughage concentration required in feedlot diets changes continuously for many reasons such as source, availability, price, and interaction with other ingredients in the diet. Wet distillers grains and solubles (WDGS) are common in finishing diets and they contain relatively high amounts of fiber compared with other grains they replace. Therefore, concentration of roughage could be altered when WDGS are included in feedlot diets. There has been very little data published regarding the effects of roughage concentration on energy metabolism and nutrient balance in beef steers. Therefore, the effects of roughage concentration in dry-rolled corn (DRC)-based diets containing 25% WDGS were evaluated in 8 steers (BW = 362 ± 3.71 kg) using a replicated Latin square. Data were analyzed with the fixed effects of dietary treatment and period and random effects of square and steer within square were included in the model. Diets consisted of 25% WDGS and the balance being DRC and coarsely ground alfalfa hay (AH) replacing corn at 2% (AH-2), 6% (AH-6), 10% (AH-10), and 14% (AH-14) of dietary dry matter. As a proportion of GE intake, fecal energy loss increased linearly (P = 0.02), and DE decreased linearly (P = 0.02) as dietary level of AH increased. Methane energy loss, as a proportion of GE intake, increased linearly (P < 0.01) and ME decreased linearly (P < 0.01) as dietary concentration of AH increased. Heat production tended (P = 0.10) to decrease reaching a minimum of 10% AH and increased from 10 to 14% AH inclusion. Moreover, as a proportion of GE intake, retained energy (RE) decreased (P < 0.01) as AH level increased in the diet. Reasons for the decrease in RE are 1) the increase in fecal energy loss that is associated with decreased ruminal digestibility of NDF when AH replaced DRC and the shift in ruminal VFA produced, 2) the decreased energy available for animal retention when NDF increased linearly as AH increased in the diet, and 3) the methane and heat

  9. Effects of decreased dietary roughage concentration on energy metabolism and nutrient balance in finishing beef cattle.

    PubMed

    Hales, K E; Brown-Brandl, T M; Freetly, H C

    2014-01-01

    The optimal roughage concentration required in feedlot diets changes continuously for many reasons such as source, availability, price, and interaction with other ingredients in the diet. Wet distillers grains and solubles (WDGS) are common in finishing diets and they contain relatively high amounts of fiber compared with other grains they replace. Therefore, concentration of roughage could be altered when WDGS are included in feedlot diets. There has been very little data published regarding the effects of roughage concentration on energy metabolism and nutrient balance in beef steers. Therefore, the effects of roughage concentration in dry-rolled corn (DRC)-based diets containing 25% WDGS were evaluated in 8 steers (BW = 362 ± 3.71 kg) using a replicated Latin square. Data were analyzed with the fixed effects of dietary treatment and period and random effects of square and steer within square were included in the model. Diets consisted of 25% WDGS and the balance being DRC and coarsely ground alfalfa hay (AH) replacing corn at 2% (AH-2), 6% (AH-6), 10% (AH-10), and 14% (AH-14) of dietary dry matter. As a proportion of GE intake, fecal energy loss increased linearly (P = 0.02), and DE decreased linearly (P = 0.02) as dietary level of AH increased. Methane energy loss, as a proportion of GE intake, increased linearly (P < 0.01) and ME decreased linearly (P < 0.01) as dietary concentration of AH increased. Heat production tended (P = 0.10) to decrease reaching a minimum of 10% AH and increased from 10 to 14% AH inclusion. Moreover, as a proportion of GE intake, retained energy (RE) decreased (P < 0.01) as AH level increased in the diet. Reasons for the decrease in RE are 1) the increase in fecal energy loss that is associated with decreased ruminal digestibility of NDF when AH replaced DRC and the shift in ruminal VFA produced, 2) the decreased energy available for animal retention when NDF increased linearly as AH increased in the diet, and 3) the methane and heat

  10. Noise power associated with decreased task-induced variability of brain electrical activity in schizophrenia.

    PubMed

    Molina, Vicente; Bachiller, Alejandro; Suazo, Vanessa; Lubeiro, Alba; Poza, Jesús; Hornero, Roberto

    2016-02-01

    In schizophrenia, both increased baseline metabolic and electroencephalographic (EEG) activities as well as decreased task-related modulation of neural dynamics have been reported. Noise power (NP) can measure the background EEG activity during task performance, and Shannon entropy (SE) is useful for quantifying the global modulation of EEG activity with a high temporal resolution. In this study, we have assessed the possible relationship between increased NP in theta and gamma bands and decreased SE modulation in 24 patients with schizophrenia and 26 controls over the parietal and central regions during a P300 task. SE modulation was calculated as the change from baseline to the active epoch (i.e., 150-550 ms following the target stimulus onset). Patients with schizophrenia displayed statistically significant higher NP values and lower SE modulation than healthy controls. We found a significant association between gamma NP and SE in all of the participants. Specifically, a NP increase in the gamma band was followed by a decrease in SE change. These results support the notion that an excess of gamma activity, unlocked to the task being performed, is accompanied by a decreased modulation of EEG activity in schizophrenia.

  11. Decreasing excessive media usage while increasing physical activity: a single-subject research study.

    PubMed

    Larwin, Karen H; Larwin, David A

    2008-11-01

    The Kaiser Family Foundation released a report entitled Kids and Media Use in the United States that concluded that children's use of media--including television, computers, Internet, video games, and phones--may be one of the primary contributor's to the poor fitness and obesity of many of today's adolescents. The present study examines the potential of increasing physical activity and decreasing media usage in a 14-year-old adolescent female by making time spent on the Internet and/or cell phone contingent on physical activity. Results of this investigation indicate that requiring the participant to earn her media-usage time did correspond with an increase in physical activity and a decrease in media-usage time relative to baseline measures. Five weeks after cessation of the intervention, the participant's new level of physical activity was still being maintained. One year after the study, the participant's level of physical activity continued to increase. PMID:18544746

  12. Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex.

    PubMed

    Amaral, A C; Jakovcevski, M; McGaughy, J A; Calderwood, S K; Mokler, D J; Rushmore, R J; Galler, J R; Akbarian, S A; Rosene, D L

    2015-02-12

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  13. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    PubMed Central

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  14. Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex.

    PubMed

    Amaral, A C; Jakovcevski, M; McGaughy, J A; Calderwood, S K; Mokler, D J; Rushmore, R J; Galler, J R; Akbarian, S A; Rosene, D L

    2015-02-12

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity.

  15. Collaboration of AMPK and PKC to induce phosphorylation of Ser413 on PIP5K1B resulting in decreased kinase activity and reduced PtdIns(4,5)P2 synthesis in response to oxidative stress and energy restriction.

    PubMed

    van den Bout, Iman; Jones, David R; Shah, Zahid H; Halstead, Jonathan R; Keune, Willem-Jan; Mohammed, Shabaz; D'Santos, Clive S; Divecha, Nullin

    2013-11-01

    The spatial and temporal regulation of the second messenger PtdIns(4,5)P2 has been shown to be crucial for regulating numerous processes in the cytoplasm and in the nucleus. Three isoforms of PIP5K1 (phosphatidylinositol 4-phosphate 5-kinase), A, B and C, are responsible for the regulation of the major pools of cellular PtdIns(4,5)P2. PIP5K1B is negatively regulated in response to oxidative stress although it remains unclear which pathways regulate its activity. In the present study, we have investigated the regulation of PIP5K1B by protein phosphorylation. Using MS analysis, we identified 12 phosphorylation sites on PIP5K1B. We developed a phospho-specific antibody against Ser413 and showed that its phosphorylation was increased in response to treatment of cells with phorbol ester, H2O2 or energy restriction. Using inhibitors, we define a stress-dependent pathway that requires the activity of the cellular energy sensor AMPK (AMP-activated protein kinase) and PKC (protein kinase C) to regulate Ser413 phosphorylation. Furthermore, we demonstrate that PKC can directly phosphorylate Ser413 in vitro. Mutation of Ser413 to aspartate to mimic serine phosphorylation decreased both PIP5K1B activity in vitro and PtdIns(4,5)P2 synthesis in vivo. Our studies show that collaboration between AMPK and PKC dictates the extent of Ser413 phosphorylation on PIP5K1B and regulates PtdIns(4,5)P2 synthesis.

  16. Sub-chronic exposure to methylmercury at low levels decreases butyrylcholinesterase activity in rats.

    PubMed

    Valentini, Juliana; Vicentini, Juliana; Grotto, Denise; Tonello, Raquel; Garcia, Solange C; Barbosa, Fernando

    2010-02-01

    In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 microg/kg/day) by gavage; (Group III) received MeHg (100 microg/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

  17. Decreased motor activity of hyperactive children on dextroamphetamine during active gym program.

    PubMed

    Rapoport, J L; Tepsic, P N; Grice, J; Johnson, C; Langer, D

    1980-07-01

    The motor activity of 10 hyperactive boys was measured during eight 1-hour active gym classes. Children received either dextroaomphetamine (0.5 mg/kg) or placebo elixir before each class, in a double-blind design. The program for each of the classes was participation in the active sports: hockey, basketball, and/or roller skating; the "task" throughout each hour was to play vigorously and continuously. The boys' mean hourly activity following amphetamine was slightly but significantly less than that following placebo. This finding is contradictory to the hypothesis that improved attention to an active task on stimulant would result in increased motor activity, and suggests the possibility of an independent direct effect of amphetamine on the motor system.

  18. Activities for Teaching Solar Energy.

    ERIC Educational Resources Information Center

    Mason, Jack Lee; Cantrell, Joseph S.

    1980-01-01

    Plans and activities are suggested for teaching elementary children about solar energy. Directions are included for constructing a flat plate collector and a solar oven. Activities for a solar field day are given. (SA)

  19. Hypoxic preconditioning decreases nuclear factor κB activity via Disrupted in Schizophrenia-1.

    PubMed

    Liu, Jia-Ren; Liu, Qian; Khoury, Joseph; Li, Yue-Jin; Han, Xiao-Hui; Li, Jing; Ibla, Juan C

    2016-01-01

    Nuclear factor κB is a key mediator of inflammation during conditions of hypoxia. Here, we used models of hypoxic pre-conditioning as mechanism to decrease nuclear factor κB activity induced by hypoxia. Our initial studies suggested that Disrupted in Schizophrenia-1 may be induced by hypoxic pre-conditioning and possibly involved in the regulation of nuclear factor κB. In this study we used Disrupted in Schizophrenia-1 exogenous over-expression and knock-down to determine its effect on ataxia telangiectasia mutated--nuclear factor κB activation cascade. Our results demonstrated that hypoxic pre-conditioning significantly increased the expression of Disrupted in Schizophrenia-1 at mRNA and protein levels both in vitro and in vivo. Over-expression of Disrupted in Schizophrenia-1 significantly attenuated the hypoxia-mediated ataxia telangiectasia mutated phosphorylation and prevented its cytoplasm translocation where it functions to activate nuclear factor κB. We further determined that Disrupted in Schizophrenia-1 activated the protein phosphatase 2A, preventing the phosphorylation of ataxia telangiectasia mutated serine-1981, the main regulatory site of ataxia telangiectasia mutated activity. Cellular levels of Disrupted in Schizophrenia-1 protein significantly decreased nuclear factor κB activation profiles and pro-inflammatory gene expression. Taken together, these results demonstrate that hypoxic pre-conditioning decreases the activation of nuclear factor κB through the transcriptional induction of Disrupted in Schizophrenia-1.

  20. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins

    PubMed Central

    Hannukainen, Jarna C; Nuutila, Pirjo; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher V˙O2,max (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)−1 min−1, P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  1. Local imipenem activity against Pseudomonas aeruginosa decreases in vivo in the presence of siliconized latex.

    PubMed

    Pichardo, C; Conejo, M C; Docobo-Pérez, F; Velasco, C; López-Rojas, R; García, I; Pachón-Ibáñez, M E; Rodríguez, J M; Pachón, J; Pascual, A

    2011-02-01

    Zinc eluted from siliconized latex (SL) increases resistance of Pseudomonas aeruginosa to imipenem in vitro. A foreign body peritonitis model was used to evaluate the activity of imipenem using SL or silicone (S) implants. No differences were observed in mortality, positive blood cultures and tissue bacterial counts between SL and S implants. Implant-associated counts, however, were significantly higher in the SL group. It is concluded that SL decreases the activity of imipenem against P. aeruginosa. PMID:20936490

  2. Decreasing Sports Activity with Increasing Age? Findings from a 20-Year Longitudinal and Cohort Sequence Analysis

    ERIC Educational Resources Information Center

    Breuer, Christoph; Wicker, Pamela

    2009-01-01

    According to cross-sectional studies in sport science literature, decreasing sports activity with increasing age is generally assumed. In this paper, the validity of this assumption is checked by applying more effective methods of analysis, such as longitudinal and cohort sequence analyses. With the help of 20 years' worth of data records from the…

  3. Limited growth of the number of sources and decrease of inelasticity in high-energy reactions

    SciTech Connect

    Weiner, R.M. ); Wilk, G. Soltan Institute for Nuclear Studies, Warsaw ); Wlodarczyk, Z. Institute of Physics, Pedagogical University, Kielce )

    1992-04-01

    The limited growth of the number of sources {l angle}{ital C}{r angle} found some time ago from the analysis of multiparticle distributions is explained in terms of the interacting gluon model. It turns out to be closely related to another characteristic property of strong interactions, namely the decrease with energy of the inelasticity {l angle}{ital K}{r angle} and is due to the specific energy dependence of the gluon-gluon cross section and the form of the gluonic structure functions.

  4. Hormone-sensitive lipase activity and triacylglycerol hydrolysis are decreased in rat soleus muscle by cyclopiazonic acid.

    PubMed

    Watt, Matthew J; Steinberg, Gregory R; Heigenhauser, G J F; Spriet, Lawrence L; Dyck, David J

    2003-08-01

    Cyclopiazonic acid (CPA) is a sarcoplasmic reticulum Ca2+-ATPase inhibitor that increases intracellular calcium. The role of CPA in regulating the oxidation and esterification of palmitate, the hydrolysis of intramuscular lipids, and the activation of hormone-sensitive lipase (HSL) was examined in isolated rat soleus muscles at rest. CPA (40 micro M) was added to the incubation medium to levels that resulted in subcontraction increases in muscle tension, and lipid metabolism was monitored using the previously described pulse-chase procedure. CPA did not alter the cellular energy state, as reflected by similar muscle contents of ATP, phosphocreatine, free AMP, and free ADP. CPA increased total palmitate uptake into soleus muscle (11%, P < 0.05) and was without effect on palmitate oxidation. This resulted in greater esterification of exogenous palmitate into the triacylglycerol (18%, P < 0.05) and phospholipid (89%, P < 0.05) pools. CPA decreased (P < 0.05) intramuscular lipid hydrolysis, and this occurred as a result of reduced HSL activity (20%, P < 0.05). Incubation of muscles with 3 mM caffeine, which is also known to increase Ca2+ without affecting the cellular energy state, reduced HSL activity (24%, P < 0.05). KN-93, a calcium/calmodulin-dependent kinase inhibitor (CaMKII), blocked the effects of CPA and caffeine, and HSL activity returned to preincubation values. The results of the present study demonstrate that CPA simultaneously decreases intramuscular triacylglycerol (IMTG) hydrolysis and promotes lipid storage in isolated, intact soleus muscle. The decreased IMTG hydrolysis is likely mediated by reduced HSL activity, possibly via the CaMKII pathway. These responses are not consistent with the increased hydrolysis and decreased esterification observed in contracting muscle when substrate availability and the hormonal milieu are tightly controlled. It is possible that more powerful signals or a higher [Ca2+] may override the lipid-storage effect of the CPA

  5. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study.

    PubMed

    Hou, Li J; Song, Zheng; Pan, Zhu J; Cheng, Jia L; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state.

  6. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study

    PubMed Central

    Hou, Li J.; Song, Zheng; Pan, Zhu J.; Cheng, Jia L.; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264

  7. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study.

    PubMed

    Hou, Li J; Song, Zheng; Pan, Zhu J; Cheng, Jia L; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264

  8. Decreased contractility due to energy deprivation in a transgenic rat model of hypertrophic cardiomyopathy.

    PubMed

    Luedde, Mark; Flögel, Ulrich; Knorr, Maike; Grundt, Christina; Hippe, Hans-Joerg; Brors, Benedikt; Frank, Derk; Haselmann, Uta; Antony, Claude; Voelkers, Mirko; Schrader, Juergen; Most, Patrick; Lemmer, Bjoern; Katus, Hugo A; Frey, Norbert

    2009-04-01

    Hypertrophic cardiomyopathy (HCM) is associated with cardiac hypertrophy, diastolic dysfunction, and sudden death. Recently, it has been suggested that inefficient energy utilization could be a common molecular pathway of HCM-related mutations. We have previously generated transgenic Sprague-Dawley rats overexpressing a truncated cardiac troponin T (DEL-TNT) molecule, displaying typical features of HCM such as diastolic dysfunction and an increased susceptibility to ventricular arrhythmias. We now studied these rats using 31P magnetic resonance spectroscopy (MRS). MRS demonstrated that cardiac energy metabolism was markedly impaired, as indicated by a decreased phosphocreatine to ATP ratio (-31%, p < 0.05). In addition, we assessed contractility of isolated cardiomyocytes. While DEL-TNT and control cardiomyocytes showed no difference under baseline conditions, DEL-TNT cardiomyocytes selectively exhibited a decrease in fractional shortening by 28% after 1 h in glucose-deprived medium (p < 0.05). Moreover, significant decreases in contraction velocity and relaxation velocity were observed. To identify the underlying molecular pathways, we performed transcriptional profiling using real-time PCR. DEL-TNT hearts exhibited induction of several genes critical for cardiac energy supply, including CD36, CPT-1/-2, and PGC-1alpha. Finally, DEL-TNT rats and controls were studied by radiotelemetry after being stressed by isoproterenol, revealing a significantly increased frequency of arrhythmias in transgenic animals. In summary, we demonstrate profound energetic alterations in DEL-TNT hearts, supporting the notion that inefficient cellular ATP utilization contributes to the pathogenesis of HCM. PMID:19189074

  9. Decreased contractility due to energy deprivation in a transgenic rat model of hypertrophic cardiomyopathy.

    PubMed

    Luedde, Mark; Flögel, Ulrich; Knorr, Maike; Grundt, Christina; Hippe, Hans-Joerg; Brors, Benedikt; Frank, Derk; Haselmann, Uta; Antony, Claude; Voelkers, Mirko; Schrader, Juergen; Most, Patrick; Lemmer, Bjoern; Katus, Hugo A; Frey, Norbert

    2009-04-01

    Hypertrophic cardiomyopathy (HCM) is associated with cardiac hypertrophy, diastolic dysfunction, and sudden death. Recently, it has been suggested that inefficient energy utilization could be a common molecular pathway of HCM-related mutations. We have previously generated transgenic Sprague-Dawley rats overexpressing a truncated cardiac troponin T (DEL-TNT) molecule, displaying typical features of HCM such as diastolic dysfunction and an increased susceptibility to ventricular arrhythmias. We now studied these rats using 31P magnetic resonance spectroscopy (MRS). MRS demonstrated that cardiac energy metabolism was markedly impaired, as indicated by a decreased phosphocreatine to ATP ratio (-31%, p < 0.05). In addition, we assessed contractility of isolated cardiomyocytes. While DEL-TNT and control cardiomyocytes showed no difference under baseline conditions, DEL-TNT cardiomyocytes selectively exhibited a decrease in fractional shortening by 28% after 1 h in glucose-deprived medium (p < 0.05). Moreover, significant decreases in contraction velocity and relaxation velocity were observed. To identify the underlying molecular pathways, we performed transcriptional profiling using real-time PCR. DEL-TNT hearts exhibited induction of several genes critical for cardiac energy supply, including CD36, CPT-1/-2, and PGC-1alpha. Finally, DEL-TNT rats and controls were studied by radiotelemetry after being stressed by isoproterenol, revealing a significantly increased frequency of arrhythmias in transgenic animals. In summary, we demonstrate profound energetic alterations in DEL-TNT hearts, supporting the notion that inefficient cellular ATP utilization contributes to the pathogenesis of HCM.

  10. Azolla filiculoides Nitrogenase Activity Decrease Induced by Inoculation with Chlamydomonas sp.

    PubMed

    Habte, M

    1986-11-01

    Experiments were conducted to determine the influence of Chlamydomonas sp. on nitrogen fixation (C(2)H(2) --> C(2)H(4)) in Azolla filiculoides and on the nitrogen fixation and growth of free-living Anabaena azollae 2B organisms. Inoculation of azolla medium with Chlamydomonas sp. was associated with decreased nitrogenase activity in A. filiculoides and with increases in the density of a fungal population identified as Acremonium sp. Subsequent inoculation of azolla medium with this fungus was also accompanied by a significant decrease in nitrogenase activity of A. filiculoides. However, the extent of depression of nitrogenase activity was significantly higher when azolla medium was inoculated with Chlamydomonas sp. than when it was inoculated with Acremonium sp. Inoculation of nitrogen-free Stanier medium with either Acremonium sp. or Chlamydomonas sp. did not adversely affect the growth or nitrogenase activity of free-living A. azollae. Decreased nitrogenase activity in A. filiculoides is apparently related to the adverse influence of the green alga and the fungus on the macrosymbiont. The mechanisms that might be involved are discussed. PMID:16347211

  11. Azolla filiculoides Nitrogenase Activity Decrease Induced by Inoculation with Chlamydomonas sp. †

    PubMed Central

    Habte, Mitiku

    1986-01-01

    Experiments were conducted to determine the influence of Chlamydomonas sp. on nitrogen fixation (C2H2 → C2H4) in Azolla filiculoides and on the nitrogen fixation and growth of free-living Anabaena azollae 2B organisms. Inoculation of azolla medium with Chlamydomonas sp. was associated with decreased nitrogenase activity in A. filiculoides and with increases in the density of a fungal population identified as Acremonium sp. Subsequent inoculation of azolla medium with this fungus was also accompanied by a significant decrease in nitrogenase activity of A. filiculoides. However, the extent of depression of nitrogenase activity was significantly higher when azolla medium was inoculated with Chlamydomonas sp. than when it was inoculated with Acremonium sp. Inoculation of nitrogen-free Stanier medium with either Acremonium sp. or Chlamydomonas sp. did not adversely affect the growth or nitrogenase activity of free-living A. azollae. Decreased nitrogenase activity in A. filiculoides is apparently related to the adverse influence of the green alga and the fungus on the macrosymbiont. The mechanisms that might be involved are discussed. PMID:16347211

  12. MIF-1 (Pro-Leu-Gly-NH2) decreases activity in Siamese fighting fish (Betta splendens).

    PubMed

    Brown, M M; Sardenga, P B; Olson, G A; Delatte, S W; Olson, R D

    1984-04-01

    The effects of MIF-1 (Pro-Leu-Gly-NH2) on activity and aggression of male Siamese Fighting Fish ( Betta splendens) were considered. Animals were given intraperitoneal injections of 0.0 or 10.0 mg/kg MIF-1. After a 10-minute delay, they were placed in a 10 gallon aquarium and their activity was monitored for 60 minutes. Although aggressive responses in the presence of suitable opponents were not reliably affected, as significant decrease in general activity was produced. This is compatible with differential effects of MIF-1 across species.

  13. Modeling of the atmospheric response to a strong decrease of the solar activity

    NASA Astrophysics Data System (ADS)

    Rozanov, Eugene V.; Egorova, Tatiana A.; Shapiro, Alexander I.; Schmutz, Werner K.

    2012-07-01

    We estimate the consequences of a potential strong decrease of the solar activity using the model simulations of the future driven by pure anthropogenic forcing as well as its combination with different solar activity related factors: total solar irradiance, spectral solar irradiance, energetic electron precipitation, solar protons and galactic cosmic rays. The comparison of the model simulations shows that introduced strong decrease of solar activity can lead to some delay of the ozone recovery and partially compensate greenhouse warming acting in the direction opposite to anthropogenic effects. The model results also show that all considered solar forcings are important in different atmospheric layers and geographical regions. However, in the global scale the solar irradiance variability can be considered as the most important solar forcing. The obtained results constitute probably the upper limit of the possible solar influence. Development of the better constrained set of future solar forcings is necessary to address the problem of future climate and ozone layer with more confidence.

  14. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  15. The ocular inflammatory response to endotoxin is not altered when glutathione peroxidase activity is decreased

    SciTech Connect

    Grimes, A.M.; McGahan, M.C.; Smith, M.G. )

    1991-03-11

    Selenium (Se) is an essential trace element and an integral part of the enzyme glutathione peroxidase (GPx). GPx is an antioxidant which scavenges both hydroperoxide and lipid peroxides. The purpose of the current study was to determine if decreased GPx activity affects the ocular inflammatory response. New Zealand White rabbits were fed either a purified Se deficient or Se adequate diet for 9 weeks. After 9 weeks, plasma Se levels were 0.151 {plus minus} 0.0130 {mu}g/ml in the deficient diet group compared to 0.217 {plus minus} 0.015 {plus minus} 0.87 U compared with 25.43 {plus minus} 1.77 U in the basal diet group. At this point, ocular inflammation was induced by intravitreal injection of endotoxin. Twenty-four hours later, despite a 40% decrease in plasma and a 30% decrease in intraocular fluid GPx activity, there was no significant difference in inflammatory parameters between the groups. However, it is possible that a further decrease in GPx activity could have some effect on the inflammatory response.

  16. Effects of decreasing sedentary behavior and increasing activity on weight change in obese children.

    PubMed

    Epstein, L H; Valoski, A M; Vara, L S; McCurley, J; Wisniewski, L; Kalarchian, M A; Klein, K R; Shrager, L R

    1995-03-01

    Obese children 8-12 years old from 61 families were randomized to treatment groups that targeted increased exercise, decreased sedentary behaviors, or both (combined group) to test the influence of reinforcing children to be more active or less sedentary on child weight change. Significant decreases in percentage overweight were observed after 4 months between the sedentary and the exercise groups (-19.9 vs. -13.2). At 1 year, the sedentary group had a greater decrease in percentage overweight than did the combined and the exercise groups (-18.7 vs. -10.3 and -8.7) and greater decrease in percentage of body fat (-4.7 vs. -1.3). All groups improved fitness during treatment and follow-up. Children in the sedentary group increased their liking for high-intensity activity and reported lower caloric intake than did children in the exercise group. These results support the goal of reducing time spent in sedentary activities to improve weight loss.

  17. Potential of activated carbon to decrease 2,4,6-trinitrotoluene toxicity and accelerate soil decontamination.

    PubMed

    Vasilyeva, G K; Kreslavski, V D; Oh, B T; Shea, P J

    2001-05-01

    Activated carbon can be used to decrease 2,4,6-trinitrotoluene (TNT) toxicity and promote bioremediation of highly contaminated soil. Adding activated carbon at 0.25, 0.75, and 1.0% (w/w) to Sharpsburg soil contaminated with 500, 1,000, and 2,000 mg TNT/kg decreased concentrations of TNT and its transformation products in soil solution to 5 mg/L or less, resulting in low toxicity to corn plants (Zea mays L.) and soil microorganisms. As much as 50% of the added TNT was rapidly bound to the soil-activated carbon matrix. Simultaneous accumulation of 2,4,6-trinitrobenzaldehyde (TNBAld) indicated that the activated carbon promoted oxidation of TNT. Some of the TNBAld was further oxidized to 1,3,5-trinitrobenzene, followed by reduction to 3,5-dinitroaniline. Reversibly bound TNT was gradually transformed to 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene, and both were bound to the soil-activated carbon matrix. The transformation and binding of TNT to soil were further promoted by incorporating shredded corn plants after growing for 52 d in the activated carbon-amended soil. After 120 d, these amendments reduced extractable TNT and transformation products by 91% in soil containing 2,000 mg TNT/kg, compared to 55% in unamended soil. These results demonstrate the potential use of activated carbon in combination with plants to promote in situ bioremediation of soils highly contaminated with explosives.

  18. Infection by bacterial pathogens expressing type III secretion decreases luciferase activity: ramifications for reporter gene studies.

    PubMed

    Savkovic, S D; Koutsouris, A; Wu, G; Hecht, G

    2000-09-01

    Pathogenic microbes influence gene regulation in eukaryotic hosts. Reporter gene studies can define the roles of promoter regulatory sequences. The effect of pathogenic bacteria on reporter genes has not been examined. The aim of this study was to identify which reporter genes are reliable in studies concerning host gene regulation by bacterial pathogens expressing type III secretory systems. Human intestinal epithelial cells, T84, Caco-2 and HT-29, were transfected with plasmids containing luciferase (luc), chloramphenicol acetyltransferase (CAT) or beta-galactosidase (beta-gal) as reporter genes driven by the inducible interleukin-8 (IL-8) or constitutively active simian virus 40 (SV40) promoter. Cells were infected with enteropathogenic E. coli or Salmonella typhimurium, and the reporter activity was assessed. Luc activity significantly decreased following infection, regardless of the promoter. The activity of recombinant luc was nearly ablated by incubation with either EPEC or Salmonella in a cell-free system. Activity was partially preserved by protease inhibitors, and immunoblot analysis showed a decreased amount and molecular weight of recombinant luc, suggesting protein degradation. Neither beta-gal nor CAT activity was altered by infection. Disruption of type III secretion prevented the loss of luc activity. We conclude that CAT or beta-gal, but not luc, can be used as reliable reporter genes to assess the impact of pathogenic microbes, especially those expressing type III secretion on host cell gene regulation.

  19. Oxidative stress is decreased in physically active sickle cell SAD mice.

    PubMed

    Charrin, Emmanuelle; Aufradet, Emeline; Douillard, Aymeric; Romdhani, Aymen; Souza, Genevieve De; Bessaad, Amine; Faes, Camille; Chirico, Erica N; Pialoux, Vincent; Martin, Cyril

    2015-03-01

    Oxidative stress plays a crucial role in sickle cell disease (SCD) physiopathology. Given that chronic physical activity is known to decrease reactive oxygen species (ROS) and increase nitric oxide (NO) bioavailability in healthy subjects and in patients with cardiovascular or inflammatory pathologies, modulating these factors involved in the severity of the pathology could also be beneficial in SCD. This study aimed to determine if 8 weeks of increased physical activity (PA) by voluntary wheel running affects the hypoxia/reoxygenation (H/R) responses by reducing oxidative stress and increasing NO synthesis in sickle SAD mice. Nitrite/nitrate (NOx) concentrations, NOS3 mRNA expression and phosphorylated-endothelial nitric oxide synthase immunostaining were increased in the lungs of the PA groups after H/R stress. Moreover, lipid peroxidation in the heart was decreased in PA SAD mice. The improvement of antioxidant activity at rest and the decrease in haemolysis may explain this reduced oxidative stress. These results suggest that physical activity probably diminishes some deleterious effects of H/R stress in SAD mice and could be protective against vascular occlusions. PMID:25382268

  20. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms

    PubMed Central

    Ji, Hong-Long; Song, Weifeng; Gao, Zhiqian; Su, Xue-Feng; Nie, Hong-Guang; Jiang, Yi; Peng, Ji-Bin; He, Yu-Xian; Liao, Ying; Zhou, Yong-Jian; Tousson, Albert; Matalon, Sadis

    2009-01-01

    Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na+) channels (ENaC), the rate-limiting protein in transepithelial Na+ vectorial transport across distal lung epithelial cells. Coexpression of either S or E protein with human α-, β-, and γ-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na+ currents and γ-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either α- or γ-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCα/β1 and PKCζ. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCα/β1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells. PMID:19112100

  1. Decrease of lactase activity in the small intestine of jejunum-bypassed rats.

    PubMed

    Shinohara, H; Goda, T; Takase, S

    1992-08-01

    The effect of jejunum-bypass operation on lactase in rat small intestine was examined. Three groups of four or five rats were designated as jejunum-bypassed, sham-operated and normal rats. All animals including normal rats received by pair-feeding 5% glucose/1% NaCl for 5 days following the operation; thereafter they were fed ad libitum the laboratory chow diet. Three weeks after the jejunal bypass operation, the proximal ileum exhibited a hyperplasia as evidenced by a concomitant increase in mucosal contents of both total proteins and DNA. The specific activity of lactase in this segment was significantly lower in the operated rats than sham-operated controls, whereas the specific activity of sucrase in this segment was significantly elevated. The reduction of lactase activity was also evident in the proximal jejunal segment as well as in the distal jejunum which was deprived of luminal nutrition, suggesting that some hormonal factor(s) might be involved in the decrease of lactase activity in jejunum-bypassed animals. Electroimmunoassay revealed that the amount of immunoreactive lactase also declined in the operated rats relative to the sham-operated controls. Our results thus suggest that lactase activity in residual ileum is not only unable to compensate for the loss of digestive-absorptive surface of jejunum, but lactase activity even decreases following jejunum-bypass operation.

  2. Decrease in respiration activity related to prodigiosin synthesis in Serratia marcescens.

    PubMed

    Kobayashi, N; Ichikawa, Y

    1985-01-01

    Variation in the cell respiration rate of pigmented and nonpigmented strains of Serratia marcescens was exhibited. The respiration rate of a pigmented strain decreased earlier than that of nonpigmented strains in the late exponential or early stationary phase. However when prodigiosin synthesis was not induced by exchange of carbon sources in the medium, the decrease in the respiration rate of the pigmented strain was the same as that of nonpigmented strains. Measurement of the oxygen consumption rate in the sonicated cell membrane by adding NADH solution showed that the rate in the pigmented strain was lower than that in nonpigmented strains. Furthermore, the cell membrane of prodigiosin-induced organisms was more sensitive to respiration inhibitors than that of pigment-noninduced organisms of the pigmented strain. These results showed that the respiration activity was decreased by prodigiosin synthesis in S. marcescens.

  3. Sleep Restriction Decreases the Physical Activity of Adults at Risk for Type 2 Diabetes

    PubMed Central

    Bromley, Lindsay E.; Booth, John N.; Kilkus, Jennifer M.; Imperial, Jacqueline G.; Penev, Plamen D.

    2012-01-01

    Study Objective: To test the hypothesis that recurrent sleep curtailment will result in decreased physical activity in adults at risk for type 2 diabetes. Design: Two-condition 2-period randomized crossover study. Setting: University General Clinical Research Center. Participants: Eighteen healthy patients with parental history of type 2 diabetes (9 females and 9 males, age 27 yr [standard deviation 3], body mass index 23.7 [2.3] kg/m2). Interventions: Two week-long inpatient sessions with 8.5 or 5.5-hr nighttime sleep opportunity. Participants who exercised regularly (39%) could follow their usual exercise routines during both sessions. Measurements and Results: Sleep and total body movement were measured by wrist actigraphy and waist accelerometry. Subjective mood and vigor was assessed using visual analog scales. The main outcome was the comparison of total activity counts between sleep conditions. Ancillary endpoints included changes in sedentary, light, and moderate plus vigorous activity, and their association with changes in mood and vigor. Daily sleep was reduced by 2.3 hr (P < 0.001) and total activity counts were 31% lower (P = 0.020) during the 5.5-hr time-in-bed condition. This was accompanied by a 24% reduction in moderate-plus-vigorous activity time (P = 0.005) and more sedentary behavior (+21 min/day; P = 0.020). The decrease in daily activity during the 5.5-hr time-in-bed condition was seen mostly in participants who exercised regularly (-39 versus −4% in exercisers versus nonexercisers; P = 0.027). Sleep loss-related declines in physical activity correlated strongly with declines in subjective vigor (R = 0.90; P < 0.001). Conclusions: Experimental sleep restriction results in decreased amount and intensity of physical activity in adults at risk for type 2 diabetes. Citation: Bromley LE; Booth JN; Kilkus JM; Imperial JG; Penev PD. Sleep restriction decreases the physical activity of adults at risk for type 2 diabetes. SLEEP 2012

  4. [Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension].

    PubMed

    Postnov, Iu V; Orlov, S N; Budnikov, E Iu; Doroshchuk, A D; Postnov, A Iu

    2008-01-01

    This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca2+ handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.) may be considered as an additional argument supporting this opinion. It means also that despite of differences in triggering mechanisms of mitochondrial dysfunction in all these models, the final outcome, i.e. decreased mitochondrial ATP production, is similar. Attenuated intracellular ATP content, in turn, results in the long-term maintenance of elevated BP by increased sympathetic outflow, whereas augmented ROS production following mitochondrial dysfunction lowers the capacity of the NO-dependent vascular relaxation. In the light of these data the cause of stationary elevated BP in chronic arterial hypertension should be regarded as a compensatory response to decreased mitochondrial ATP synthesis.

  5. Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension.

    PubMed

    Postnov, Yuvenalii V; Orlov, Sergei N; Budnikov, Yegor Y; Doroschuk, Alexander D; Postnov, Anton Y

    2007-12-01

    Despite numerous efforts, including recent genetic and molecular biology studies, the immediate cause of stationary elevated blood pressure (BP) in any kind of hypertension has not been satisfactorily explained. This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca(2+) handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.) may be considered as an additional argument supporting this opinion. It means also that despite of differences in triggering mechanisms of mitochondrial dysfunction in all these models, the final outcome, i.e. decreased mitochondrial ATP production, is similar. Attenuated intracellular ATP content, in turn, results in the long-term maintenance of elevated BP by increased sympathetic outflow, whereas augmented ROS production following mitochondrial dysfunction lowers the capacity of the NO-dependent vascular relaxation. In the light of these data the cause of stationary elevated BP in chronic arterial hypertension should be regarded as a compensatory response to decreased mitochondrial ATP synthesis.

  6. Increasing or decreasing interest in activities: the role of regulatory fit.

    PubMed

    Higgins, E Tory; Cesario, Joseph; Hagiwara, Nao; Spiegel, Scott; Pittman, Thane

    2010-04-01

    What makes people's interest in doing an activity increase or decrease? Regulatory fit theory (E. T. Higgins, 2000) provides a new perspective on this classic issue by emphasizing the relation between people's activity orientation, such as thinking of an activity as fun, and the manner of activity engagement that the surrounding situation supports. These situational factors include whether a reward for good performance, expected (Study 1) or unexpected (Study 2), is experienced as enjoyable or as serious and whether the free-choice period that measures interest in the activity is experienced as enjoyable or as serious (Study 3). Studies 1-3 found that participants were more likely to do a fun activity again when these situational factors supported a manner of doing the activity that fit the fun orientation-a reward or free-choice period framed as enjoyable. This effect was not because interest in doing an activity again is simply greater in an enjoyable than a serious surrounding situation because it did not occur, and even reversed, when the activity orientation was important rather than fun, where now a serious manner of engagement provides the fit (Study 4a and 4b).

  7. Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids

    PubMed Central

    Guimarães, Larissa O.; de Andrade, Fabiana A.; Bono, Gleyse F.; Setoguchi, Thaís E.; Brandão, Mariana B.; Chautard-Freire-Maia, Eleidi A.; dos Santos, Izabella C.R.; Picheth, Geraldo; Faria, Ana Cristina R. de A.; Réa, Rosângela R.; Souza, Ricardo L.R.; Furtado-Alle, Lupe

    2014-01-01

    Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g., pregnancy or presence of the BCHE gene variant −116A can decrease activity whereas obesity and types I and II diabetes mellitus can increase activity. In this study, we examined BChE activity, −116A and 1615A BCHE gene variants, and anthropometric and biochemical variables associated with diabetes in patients with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE activity was measured spectrophotometrically using propionylthiocholine as substrate and genotyping of the −116 and 1615 sites of the BCHE gene was done with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE activity was significantly lower in healthy pregnant women than in women from the general population and was further reduced in GDM patients. BChE activity was significantly reduced in carriers of −116A in GDM patients and healthy pregnant women. Although GDM patients had a significantly higher mean body mass index (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE activity, suggesting that the lowering effect of GDM on BChE activity was stronger than the characteristic enhancing effect of increased BMI and triglycerides. PMID:24688284

  8. Decreased electrophysiological activity represents the conscious state of emptiness in meditation.

    PubMed

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful "thoughtless emptiness (TE)," a "focused attention," and an "open monitoring" task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p < 0.05). Compared to open monitoring TE expressed decreased alpha and beta amplitudes, mainly in parietal areas (p < 0.01). TE presented significantly less delta (p < 0.001) and theta (p < 0.05) waves than a wakeful closed eyes resting condition. A group of participants with none or little meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness.

  9. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    PubMed Central

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful “thoughtless emptiness (TE),” a “focused attention,” and an “open monitoring” task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p < 0.05). Compared to open monitoring TE expressed decreased alpha and beta amplitudes, mainly in parietal areas (p < 0.01). TE presented significantly less delta (p < 0.001) and theta (p < 0.05) waves than a wakeful closed eyes resting condition. A group of participants with none or little meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  10. Stacking fault energy decrease in austenitic stainless steels induced by hydrogen pairs formation

    SciTech Connect

    Hermida, J.D.; Roviglione, A.

    1998-09-15

    The decrease of the Stacking Fault Energy (SFE), induced by hydrogen in austenitic stainless steels, was always invoked to explain the formation of {epsilon}-martensite at room temperature during cathodic charging of hydrogen. Pontini and Hermida measured by XRD a reduction of 37 pct of the SPE of an AISI 304 steel at room temperature, in the presence of only 274 ppm of hydrogen. However, the nature of this phenomenon is still unknown. Recently, Obiol et a., using the Atoms Superposition and Electron Delocalization-Molecular Obital (ASED-MO) method, calculated the binding energy for H-H pair formation in the faulted zone of an FCC iron matrix. It was shown that, the H-H pair formation is more likely to occur along directions connecting octahedral interstices of the HCP stacking sequence and that are normal to the {l_brace}111{r_brace} planes. The binding energy found was {minus}5.75 eV, being this value significantly larger than the corresponding one for vacuum: {minus}4.75 eV. In this work, an explanation of the SFE decrease is developed on the basis of this previous result.

  11. Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice

    PubMed Central

    Drougard, Anne; Fournel, Audren; Marlin, Alysson; Meunier, Etienne; Abot, Anne; Bautzova, Tereza; Duparc, Thibaut; Louche, Katie; Batut, Aurelie; Lucas, Alexandre; Le-Gonidec, Sophie; Lesage, Jean; Fioramonti, Xavier; Moro, Cedric; Valet, Philippe; Cani, Patrice D.; Knauf, Claude

    2016-01-01

    Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning. PMID:27549402

  12. Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.

    PubMed

    Drougard, Anne; Fournel, Audren; Marlin, Alysson; Meunier, Etienne; Abot, Anne; Bautzova, Tereza; Duparc, Thibaut; Louche, Katie; Batut, Aurelie; Lucas, Alexandre; Le-Gonidec, Sophie; Lesage, Jean; Fioramonti, Xavier; Moro, Cedric; Valet, Philippe; Cani, Patrice D; Knauf, Claude

    2016-01-01

    Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning. PMID:27549402

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

    PubMed

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

    2015-09-01

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

  14. Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes.

    PubMed

    Li, Wan-Fen; Pan, Mei-Hung; Chung, Meng-Chu; Ho, Chi-Kung; Chuang, Hung-Yi

    2006-08-01

    Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, -108C/T). The mean blood lead level (+/-SD) of this cohort was 27.1+/-15 microg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p<0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele.

  15. Exercise Decreases Risk of Future Active Disease in Inflammatory Bowel Disease Patients in Remission

    PubMed Central

    Jones, Patricia D.; Kappelman, Michael D.; Martin, Christopher F.; Chen, Wenli; Sandler, Robert S.; Long, Millie D.

    2015-01-01

    Background Although exercise impacts quality of life in patients with inflammatory bowel disease (IBD), little is known about its role in disease activity. Among IBD patients in remission, we aimed to evaluate the association between exercise and subsequent active disease. Methods We performed a prospective study using the Crohn's and Colitis Foundation of America (CCFA) Partners Internet-based cohort of individuals with self-reported IBD. We identified participants in remission, defined as short Crohn's disease activity index (sCDAI) <150 or simple clinical colitis activity index (SCCAI) ≤2. The primary exposure was exercise status, measured using the validated Godin leisure time activity index. The primary study outcome, assessed after six months, was active disease defined using the above disease activity index thresholds. We used bivariate and multivariate analyses to describe the independent association between exercise and risk of active disease. Results We identified 1308 patients with Crohn's Disease (CD) and 549 with ulcerative or indeterminate colitis (UC/IC) in remission, of whom 227(17.4%) with CD and 135 (24.6%) with UC/IC developed active disease after 6 months. Higher exercise level was associated with decreased risk of active disease for CD (adjusted RR 0.72, 95% CI 0.55-0.94) and UC/IC (adjusted RR 0.78, 95% CI 0.54-1.13). Conclusions In patients with CD in remission, those with higher exercise levels were significantly less likely to develop active disease at six months. In patients with UC/IC in remission, patients with higher exercise levels were less likely to develop active disease at six months, however this was not statistically significant. PMID:25723616

  16. Cell Motility Is Decreased in Macrophages Activated by Cancer Cell-Conditioned Medium

    PubMed Central

    Go, Ahreum; Ryu, Yun-Kyoung; Lee, Jae-Wook; Moon, Eun-Yi

    2013-01-01

    Macrophages play a role in innate immune responses to various foreign antigens. Many products from primary tumors influence the activation and transmigration of macrophages. Here, we investigated a migration of macrophages stimulated with cancer cell culture-conditioned medium (CM). Macrophage activation by treatment with CM of B16F10 cells were judged by the increase in protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). The location where macrophages were at 4 h-incubation with control medium or CM was different from where they were at 5 h-incubation in culture dish. Percentage of superimposed macrophages at every 1 h interval was gradually increased by CM treatment as compared to control. Total coverage of migrated track expressed in coordinates was smaller and total distance of migration was shorter in CM-treated macrophages than that in control. Rac1 activity in CM-treated macrophages was also decreased as compared to that in control. When macrophages were treated with CM in the presence of dexamethasone (Dex), an increase in COX2 protein levels, and a decrease in Rac1 activity and total coverage of migration were reversed. In the meanwhile, biphasic changes were detected by Dex treatment in section distance of migration at each time interval, which was more decreased at early time and then increased at later time. Taken together, data demonstrate that macrophage motility could be reduced in accordance with activation in response to cancer cell products. It suggests that macrophage motility could be a novel marker to monitor cancer-associated inflammatory diseases and the efficacy of anti-inflammatory agents. PMID:24404340

  17. Does the mass of a black hole decrease due to the accretion of phantom energy?

    SciTech Connect

    Gao Changjun; Chen Xuelei; Faraoni, Valerio; Shen Yougen

    2008-07-15

    According to Babichev et al., the accretion of a phantom test fluid onto a Schwarzschild black hole will induce the mass of the black hole to decrease, however the backreaction was ignored in their calculation. Using new exact solutions describing black holes in a background Friedmann-Robertson-Walker universe, we find that the physical black hole mass may instead increase due to the accretion of phantom energy. If this is the case, and the future universe is dominated by phantom dark energy, the black hole apparent horizon and the cosmic apparent horizon will eventually coincide and, after that, the black hole singularity will become naked in finite comoving time before the big rip occurs, violating the cosmic censorship conjecture.

  18. Music Attenuated a Decrease in Parasympathetic Nervous System Activity after Exercise

    PubMed Central

    Miura, Misa; Ito, Osamu; Kohzuki, Masahiro

    2016-01-01

    Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post-exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post-exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise. PMID:26840532

  19. Music Attenuated a Decrease in Parasympathetic Nervous System Activity after Exercise.

    PubMed

    Jia, Tiantian; Ogawa, Yoshiko; Miura, Misa; Ito, Osamu; Kohzuki, Masahiro

    2016-01-01

    Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post-exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post-exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise.

  20. Selective decrease of Na+/k+ -ATPase activity in the brain of hypothyroid rats.

    PubMed

    Pacheco-Rosado, Jorge; Arias-Citalán, G; Ortiz-Butrón, R; Rodríquez-Páez, L

    2005-01-01

    The present work was performed in order to know if mild hypothyroidism in rats modifies the activity of the Na+/K+ -ATPase in different regions of the brain. Male Wistar rats (300-350 g) were randomly divided into three groups: (1) control group (n=8) drank tap water. (2) hypothyroid group (n=8) treated with 60 mg/kg of methimazole in drinking water; and (3) replaced group (n=8) treated with 60 mg/kg of methimazole plus 35 microg/kg of thyroid hormone (T3) in drinking water. After four weeks of treatment, the rats of all groups were sacrificed by decapitation. The cortex, amygdala, hippocampus and cerebellum were dissected and frozen at -70 degrees C until assay. For enzymatic assay, the tissues were homogenized. The Na+/K+ -ATPase activity was determined by quantifying inorganic phosphate after the samples were incubated with ATP in the presence and absence of 1 mM ouabain. The Na+/K+ -ATPase activity is expressed as pmoles Pi/hr/mg protein. The results showed that the Na+/K+ -ATPase activity in the cortex, amygdala and hippocampus, but not in cerebellum, was lower in hypothyroid group than in control group (p<0.05). The co-administration of methimazole and T3 avoided the decrease of Na+/K+ -ATPase activity, except in amygdala. According to the results obtained we concluded that methimazole treatment decreased the Na+/K+- ATPase activity in the brain's regions which are related to seizures onset. That decrement in enzyme activity was avoided with the coadministration of thyroid hormone.

  1. Membrane-bound complement regulatory activity is decreased on vaccinia virus-infected cells.

    PubMed Central

    Baranyi, L; Okada, N; Baranji, K; Takizawa, H; Okada, H

    1994-01-01

    Decay accelerating factor (DAF), membrane cofactor protein (MCP), complement receptor 1 and mouse Crry are cell surface-bound complement regulatory proteins capable of inhibiting C3 convertase activity on cell membranes, and therefore provide a substantial protection from attack by homologous complement activated either by the classical or by the alternative pathway. Decrease in complement regulatory activity might lead to spontaneous complement deposition and subsequent cell injury. MoAb 5I2 can inhibit the complement regulatory activity of molecules on rat cells, resulting in deposition of homologous complement. The antigen recognized by 5I2 MoAb in rats is homologous to mouse Crry. Fifteen to 20 h after infection with vaccinia virus, in vitro cultured KDH-8 rat hepatoma cells show a strong decrease in expression of Crry-like antigen, and proved to be sensitive to complement deposition when 1:5 diluted normal rat serum was added to the culture medium as a source of complement. Addition of complement to the cultured KDH-8 cells infected with a very low dose of vaccinia virus (1 plaque-forming unit (PFU)/1000 cells) substantially reduced spreading of virus infection in the cell culture, while inactivation of complement by heat or zymosan treatment abrogated the protective effect. PMID:7923872

  2. Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi

    2007-02-28

    Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress. PMID:17291597

  3. Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder

    PubMed Central

    Kassel, Michelle T.; Rao, Julia A.; Walker, Sara J.; Briceño, Emily M.; Gabriel, Laura B.; Weldon, Anne L.; Avery, Erich T.; Haase, Brennan D.; Peciña, Marta; Considine, Ciaran M.; Noll, Douglas C.; Bieliauskas, Linas A.; Starkman, Monica N.; Zubieta, Jon-Kar; Welsh, Robert C.; Giordani, Bruno; Weisenbach, Sara L.; Langenecker, Scott A.

    2016-01-01

    Objective Individuals with Major Depressive Disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Method Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during fMRI. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. Results MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Conclusions Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. PMID:26831638

  4. Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer’s Disease Pathology

    PubMed Central

    Rosenberger, Andrea F.N.; Hilhorst, Riet; Coart, Elisabeth; García Barrado, Leandro; Naji, Faris; Rozemuller, Annemieke J.M.; van der Flier, Wiesje M.; Scheltens, Philip; Hoozemans, Jeroen J.M.; van der Vies, Saskia M.

    2015-01-01

    Alzheimer’s disease (AD) is characterized by a long pre-clinical phase (20–30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention. PMID:26519433

  5. Experimental evaluation of decrease in the activities of polyphosphate/glycogen-accumulating organisms due to cell death and activity decay in activated sludge.

    PubMed

    Hao, Xiaodi; Wang, Qilin; Cao, Yali; van Loosdrecht, Mark C M

    2010-06-15

    Decrease in bacterial activity (biomass decay) in activated sludge can result from cell death (reduction in the amount of active bacteria) and activity decay (reduction in the specific activity of active bacteria). The goal of this study was to experimentally differentiate between cell death and activity decay as the cause of decrease in bacterial activity. By means of measuring maximal anaerobic phosphate release rates, verifying membrane integrity by live/dead staining and verifying presence of 16S rRNA with fluorescence in situ hybridization (FISH), the decay rates and death rates of polyphosphate-accumulating organisms (PAOs) in a biological nutrient removal (BNR) system and a laboratory phosphate removing sequencing batch reactor (SBR) system were determined, respectively, under famine conditions. In addition, the decay rate and death rate of glycogen-accumulating organisms (GAOs) in a SBR system with an enrichment culture of GAOs were also measured under famine conditions. Hereto the maximal anaerobic volatile fatty acid uptake rates, live/dead staining, and FISH were used. The experiments revealed that in the BNR and enriched PAO-SBR systems, activity decay contributed 58% and 80% to the decreased activities of PAOs, and that cell death was responsible for 42% and 20% of decreases in their respective activities. In the enriched GAOs system, activity decay constituted a proportion of 74% of the decreased activity of GAOs, and cell death only accounted for 26% of the decrease of their activity.

  6. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    PubMed

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens.

  7. Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls

    PubMed Central

    Johnson, Kyle B.; Hitomi, Kiyotaka; Tykocki, Nathan R.; Thompson, Janice M.; Watts, Stephanie W.

    2015-01-01

    Transglutaminases (TGs) catalyze the formation of covalent cross-links between glutamine residues and amine groups. This cross-linking activity has been implicated in arterial remodeling. Because hypertension is characterized by arterial remodeling, we hypothesized that TG activity, expression, and functionality would be increased in the aorta, but not in the vena cava (which does not undergo remodeling), from hypertensive rats relative to normotensive rats. Spontaneously hypertensive stroke-prone rats (SHRSP) and DOCA-salt rats as well as their respective normotensive Wistar-Kyoto or Sprague-Dawley counterparts were used. Immunohistochemistry and Western blot analysis measured the presence and expression of TG1 and TG2, in situ activity assays quantified active TGs, and isometric contractility was used to measure TG functionality. Contrary to our hypothesis, the activity (52% DOCA-salt vs. control rats and 56% SHRSP vs. control rats, P < 0.05), expression (TG1: 54% DOCA-salt vs. control rats, P > 0.05, and TG2: 77% DOCA-salt vs. control rats, P < 0.05), and functionality of TG1 and TG2 were decreased in the aorta, but not in the vena cava, from hypertensive rats. Mass spectrometry identified proteins uniquely amidated by TGs in the aorta that play roles in cytoskeletal regulation, redox regulation, and DNA/RNA/protein synthesis and regulation and in the vena cava that play roles in cytoskeletal regulation, coagulation regulation, and cell metabolism. Consistent with the idea that growing cells lose TG2 expression, vascular smooth muscle cells placed in culture lost TG2 expression. We conclude that the expression, activity, and functionality of TG1 and TG2 are decreased in the aorta, but not in the vena cava, from hypertensive rats compared with control rats. PMID:25599570

  8. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

    PubMed Central

    Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2016-01-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

  9. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    PubMed

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

  10. Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis.

    PubMed

    Slavov, Nikolai; Budnik, Bogdan A; Schwab, David; Airoldi, Edoardo M; van Oudenaarden, Alexander

    2014-05-01

    Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration) and of mitochondrial folate-mediated NADPH production (required for oxidative defense). The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival.

  11. Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae.

    PubMed

    Barros, Mario H; Bandy, Brian; Tahara, Erich B; Kowaltowski, Alicia J

    2004-11-26

    Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

  12. Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients.

    PubMed

    Chrapko, Wendy; Jurasz, Paul; Radomski, Marek W; Archer, Stephen L; Newman, Stephen C; Baker, Glen; Lara, Nathalie; Le Mellédo, Jean-Michel

    2006-06-01

    Although major depression (MD) and cardiovascular disease (CVD) have been conclusively linked in the literature, the mechanism associating MD and CVD is yet undetermined. The purpose of this paper is to further investigate a potential mechanism involving nitric oxide (NO) and to examine the effect of the selective serotonin reuptake inhibitor paroxetine on NO production by both platelets and the endothelium. In total, 17 subjects with MD and 12 healthy controls (HCs) with no known history of cardiovascular illness completed the study. Paroxetine was administered to both the MD patients and HCs over an 8-week period, and then medication was discontinued. Blood samples were taken at various times throughout paroxetine treatment and after discontinuation. Plasma NO metabolite (NOx) levels were measured by a chemiluminescence method. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of L-[14C]arginine to L-[(14)C]citrulline. Data were analyzed using t-tests and a linear mixed effects model. Baseline levels of both plasma NOx and platelet NOS activity were significantly lower in subjects with MD compared to HCs. Throughout paroxetine treatment, plasma NOx levels increased in both HCs and MD patients. However, platelet eNOS activity decreased in HCs, while no statistically significant change was evidenced in MD patients. These data suggest that, in MD patients, decreased peripheral production of NO, a potential contributor to increased cardiovascular risk, is modified by administration of the antidepressant paroxetine. PMID:16319917

  13. Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity.

    PubMed

    Greco, Tiffany; Glenn, Thomas C; Hovda, David A; Prins, Mayumi L

    2016-09-01

    Cerebral metabolism of ketones after traumatic brain injury (TBI) improves neuropathology and behavior in an age-dependent manner. Neuroprotection is attributed to improved cellular energetics, although other properties contribute to the beneficial effects. Oxidative stress is responsible for mitochondrial dysfunction after TBI. Ketones decrease oxidative stress, increase antioxidants and scavenge free radicals. It is hypothesized that ketogenic diet (KD) will decrease post-TBI oxidative stress and improve mitochondria. Postnatal day 35 (PND35) male rats were given sham or controlled cortical impact (CCI) injury and placed on standard (STD) or KD. Ipsilateral cortex homogenates and mitochondria were assayed for markers of oxidative stress, antioxidant expression and mitochondrial function. Oxidative stress was significantly increased at 6 and 24 h post-injury and attenuated by KD while inducing protein expression of antioxidants, NAD(P)H dehydrogenase quinone 1 (NQO1) and superoxide dismutase (SOD1/2). Complex I activity was inhibited in STD and KD groups at 6 h and normalized by 24 h. KD significantly improved Complex II-III activity that was reduced in STD at 6 h. Activity remained reduced at 24 h in STD and unchanged in KD animals. These results strongly suggest that ketones improve post-TBI cerebral metabolism by providing alternative substrates and through antioxidant properties, preventing oxidative stress-mediated mitochondrial dysfunction.

  14. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    PubMed

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. PMID:26295691

  15. Antinociceptive activity of (-)-carvone: evidence of association with decreased peripheral nerve excitability.

    PubMed

    Gonçalves, Juan Carlos Ramos; Oliveira, Fernando de Sousa; Benedito, Rubens Batista; de Sousa, Damião Pergentino; de Almeida, Reinaldo Nóbrega; de Araújo, Demetrius Antônio Machado

    2008-05-01

    (-)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (-)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (-)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (-)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (-)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (-)-carvone. Such results were unlikely to be provoked by motor abnormality, since (-)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (-)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (-)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability.

  16. Technologies for decreasing the tap temperature to save energy in steel foundries

    NASA Astrophysics Data System (ADS)

    Biswas, Siddhartha

    Steel foundries are one of the most energy intensive industries. The increasing concerns over volatile energy cost and carbon dioxide emission have pushed foundries to improve efficiency and hence decrease electrical energy consumption. Statistical analysis of industrial survey data was combined with computational fluid dynamics (CFD) modeling to investigate the best industrial practices and opportunities to improve energy efficiency. Reducing tap temperature was identified as one of the important ways of reducing energy consumption. Steel foundries typically tap at 1650-1800°C (3000-3300°F) which is 100-250°C (150-450°F) higher than the pouring temperature. The steel temperature is elevated to compensate for the temperature loss associated with tapping, holding and transporting the liquid steel from the furnace to the pouring floor. Based on experimental investigations and CFD modeling of heat losses during holding in the ladle for different foundry practices, a spreadsheet calculator has been developed to calculate the optimum tap temperature for the specific foundry practices which will eliminate unnecessary superheating. The calculated results were compared and validated with industrial measurements. Improving the lining refractory is one significant way of reducing heat losses during holding of the steel in ladle. Silica sand linings are being used in steel foundries as an inexpensive and convenient material for short holding times and small volumes. The possibilities of improvements of silica sand linings by the addition of lower density cenospheres (hollow spheres), a byproduct of coal fired power plants, was studied through property measurements and laboratory trials.

  17. Eating slowly led to decreases in energy intake within meals in healthy women.

    PubMed

    Andrade, Ana M; Greene, Geoffrey W; Melanson, Kathleen J

    2008-07-01

    Although reducing eating rate is frequently advocated for control of food intake and thus body weight, empirical evidence is extremely limited and inconsistent. We sought to compare the impact of slow and quick eating rates on development of satiation in healthy women. In a randomized design, 30 healthy women (22.9+/-7.1 years; body mass index [calculated as kg/m(2)] 22.1+/-2.9) were studied on two test visits to compare slow and quick eating rates. Satiation was examined as the main outcome, using the objective measure of energy intake during ad libitum meals. At designated times, subjects also rated perceived hunger, satiety, desire to eat, thirst and meal palatability on visual analogue scales. Slow rates of ingestion led to significant decreases in energy intake (quick: 645.7+/-155.9 kcal; slow: 579.0+/-154.7 kcal; P<0.05) and significant increases in water consumption (quick: 289.9+/-155.1 g; slow: 409.6+/-205.8 g; P<0.05). Despite higher energy intake upon meal completion under the quick condition, satiety was significantly lower than the slow condition (P<0.05). Accordingly, the quick condition showed a lower Satiating Efficiency Index (quick: 0.1; slow: 0.2; P<0.05). After meal completion, pleasantness ratings tended to be higher under the slow condition (P=0.04; but not significant after Bonferroni adjustment). Ad libitum energy intake was lower when the meal was eaten slowly, and satiety was higher at meal completion. Although more study is needed, these data suggest that eating slowly may help to maximize satiation and reduce energy intake within meals.

  18. Ergonomics work stations decreases the health impairment and saves electrical energy at the woodworking workshop in Bali, Indonesia.

    PubMed

    Sudiajeng, Lilik; Adiputra, Nyoman; Leibbrandt, Richard

    2012-12-01

    This research was conducted to assess the positive effect of the ergonomics work station on the health impairment and electrical energy usage at the woodworking workshop in Bali, Indonesia. Woodworking workshops are dangerous, particularly when they are used improperly. Workers are exposed to health hazards that cause health impairment and inefficiencies in their work conditions. A preliminary study at a woodworking workshop at the Bali State Polytechnic showed that the work station was not suitable to body size of the participants and caused awkward postures. In addition, there was also an inappropriate physical work environment. Both inappropriate work station and physical work environment caused participants to be less active and motivated. This paper reports on an experimental study into the effects of an ergonomic intervention at this workshop. The participants were 2 groups of male students with 10 participants in each group. The first group performed the task with the original work station as a control group, while the second group performed the task with the new work station. The study found a significant difference between groups (p < 0.05) both for the health impairment and the electrical energy usage. The ergonomics intervention on the work station decreased the working heart rate (16.7%), the total score of musculoskeletal disorders (17.3%), and the total score of psychological fatigue (21.5%). Furthermore, it also decreased the electrical energy usage (38.7%). This shows that an ergonomics intervention on work station decreased the health impairment and saved electrical energy usage. It also protected the workers from woodworking hazards and allowed participants to perform their tasks in healthy, safe, convenient and efficient work conditions.

  19. Topical Application of Ice-Nucleating-Active Bacteria Decreases Insect Cold Tolerance †

    PubMed Central

    Strong-Gunderson, Janet M.; Lee, Richard E.; Lee, Marcia R.

    1992-01-01

    The majority of overwintering insects avoid lethal freezing by lowering the temperature at which ice spontaneously nucleates within their body fluids. We examined the effect of ice-nucleating-active bacteria on the cold-hardiness of the lady beetle, Hippodamia convergens, a freeze-intolerant species that overwinters by supercooling to ca. −16°C. Topical application of the ice-nucleating-active bacteria Pseudomonas syringae increased the supercooling point to temperatures as high as −3°C. This decrease in cold tolerance was maintained for at least 3 days after treatment. Various treatment doses (108, 106, and 104 bacteria per ml) and modes of action (bacterial ingestion and topical application) were also compared. At the highest concentration of topically applied P. syringae, 50% of the beetles froze between −2 and −4°C. After topical application at the lowest concentration, 50% of the individuals froze by −11°C. In contrast, beetles fed bacteria at this concentration did not begin to freeze until −10°C, and 50% were frozen only at temperatures of −13°C or less. In addition to reducing the supercooling capacity in H. convergens, ice-nucleating-active bacteria also significantly reduced the cold-hardiness of four additional insects. These data demonstrate that ice-nucleating-active bacteria can be used to elevate the supercooling point and thereby decrease insect cold tolerance. The results of this study support the proposition that ice-nucleating-active bacteria may be used as a biological insecticide for the control of insect pests during the winter. Images PMID:16348764

  20. Using an Alternate Reality Game to Increase Physical Activity and Decrease Obesity Risk of College Students

    PubMed Central

    Johnston, Jeanne D.; Massey, Anne P.; Marker-Hoffman, Rickie Lee

    2012-01-01

    Background This quasi-experimental study investigated a game intervention—specifically, an alternate reality game (ARG)—as a means to influence college students’ physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story. Method Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week). Results A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p < .001) versus a significant decrease (p = .001) for the comparison group. Significant within-group increases for weight (p = .001), BMI (p = .001), and PBF (p = .001) were detected. A significant group x time interaction (p = .001) was detected when analyzing self-reported VPA, with both groups reporting decreases in VPA over time; however, the decrease was only significant for the comparison group (p < .001). No significant group differences were found for MPA. Conclusions It is important that any intervention meet the needs and interests of its target population. Here, the ARG was designed in light of the learning preferences of today’s college students—collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population. PMID:22920809

  1. The Experimental Research (In Vitro) of Carrageenans and Fucoidans to Decrease Activity of Hantavirus.

    PubMed

    Pavliga, Stanislav N; Kompanets, Galina G; Tsygankov, Vasiliy Yu

    2016-06-01

    The effect of carrageenans and fucoidans on the activity of Hantavirus is studied. It has been found that among carrageenans a significant antiviral effect is exerted by the ι-type, which decreases the viral titer by 2.5 log focus forming units per mL; among fucoidans, by a preparation from Laminaria cichorioides, which reduces the number of infected cells from 27.0 to 5.3 after pretreatment of both the macrophage culture and Hantavirus. The antiviral effect of fucoidan from Laminaria japonica is shown to grow in direct proportion to the increase of dose of the preparation. PMID:26943130

  2. Activation of Mitochondrial Uncoupling Protein 4 and ATP-Sensitive Potassium Channel Cumulatively Decreases Superoxide Production in Insect Mitochondria.

    PubMed

    Slocińska, Malgorzata; Rosinski, Grzegorz; Jarmuszkiewicz, Wieslawa

    2016-01-01

    It has been evidenced that mitochondrial uncoupling protein 4 (UCP4) and ATP-regulated potassium channel (mKATP channel) of insect Gromphadorhina coqereliana mitochondria decrease superoxide anion production. We elucidated whether the two energy-dissipating systems work together on a modulation of superoxide level in cockroach mitochondria. Our data show that the simultaneous activation of UCP4 by palmitic acid and mKATP channel by pinacidil revealed a cumulative effect on weakening mitochondrial superoxide formation. The inhibition of UCP4 by GTP (and/or ATP) and mKATP channel by ATP elevated superoxide production. These results suggest a functional cooperation of both energy-dissipating systems in protection against oxidative stress in insects.

  3. A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance.

    PubMed

    Resch, Gregory; Moreillon, Philippe; Fischetti, Vincent A

    2011-12-01

    Bacteriophages (phages) produce endolysins (lysins) as part of their lytic cycle in order to degrade the peptidoglycan layer of the infected bacteria for subsequent release of phage progeny. Because these enzymes maintain their lytic and lethal activity against Gram-positive bacteria when added extrinsically to the cells, they have been actively exploited as novel anti-infectives, sometimes termed enzybiotics. As with other relatively small peptides, one issue in their clinical development is their rapid inactivation through proteolytic degradation, immunological blockage and renal clearance. The antipneumococcal lysin Cpl-1 was shown to escape both proteolysis and immunological blockage. However, its short plasma half-life (20.5 min in mice) may represent a shortcoming for clinical usefulness. Here we report the construction of a Cpl-1 dimer with a view to increasing both the antipneumococcal specific activity and plasma half-life of Cpl-1. Dimerisation was achieved by introducing specific cysteine residues at the C-terminal end of the enzyme, thus favouring disulphide bonding. Compared with the native monomer, the constructed dimer demonstrated a two-fold increase in specific antipneumococcal activity and a ca. ten-fold decrease in plasma clearance. As several lysins are suspected to dimerise on contact with their cell wall substrate to be fully active, stable pre-dimerised enzymes may represent a more efficient alternative to the native monomer. PMID:21982146

  4. Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation.

    PubMed

    Maeno, Emi; Tsubata, Takeshi; Okada, Yasunobu

    2012-12-05

    Persistent cell shrinkage is a major hallmark of apoptotic cell death. The early-phase shrinkage, which starts within 30-120 min after apoptotic stimulation and is called apoptotic volume decrease (AVD), is known to be accomplished by activation of K+ channels and volume-sensitive outwardly rectifying (VSOR) Cl- channels in a manner independent of caspase-3 activation. However, it is controversial whether AVD depends on apoptotic dysfunction of mitochondria and activation of initiator caspases. Here, we observed that AVD is induced not only by a mitochondrial apoptosis inducer, staurosporine (STS), in mouse B lymphoma WEHI-231 cells, but also by ligation of the death receptor Fas in human B lymphoblastoid SKW6.4 cells, which undergo Fas-mediated apoptosis without involving mitochondria. Overexpression of Bcl-2 failed to inhibit the STS-induced AVD in WEHI-231 cells. These results indicate that AVD does not require the mitochondrial pathway of apoptosis. In human epithelial HeLa cells stimulated with anti-Fas antibody or STS, the AVD induction was found to precede activation of caspase-8 and caspase-9 and to be resistant to pan-caspase blockers. Thus, it is concluded that the AVD induction is an early event independent of the mitochondrial apoptotic signaling pathway and initiator caspase activation.

  5. Chemical activation through super energy transfer collisions.

    PubMed

    Smith, Jonathan M; Nikow, Matthew; Ma, Jianqiang; Wilhelm, Michael J; Han, Yong-Chang; Sharma, Amit R; Bowman, Joel M; Dai, Hai-Lung

    2014-02-01

    Can a molecule be efficiently activated with a large amount of energy in a single collision with a fast atom? If so, this type of collision will greatly affect molecular reactivity and equilibrium in systems where abundant hot atoms exist. Conventional expectation of molecular energy transfer (ET) is that the probability decreases exponentially with the amount of energy transferred, hence the probability of what we label "super energy transfer" is negligible. We show, however, that in collisions between an atom and a molecule for which chemical reactions may occur, such as those between a translationally hot H atom and an ambient acetylene (HCCH) or sulfur dioxide, ET of chemically significant amounts of energy commences with surprisingly high efficiency through chemical complex formation. Time-resolved infrared emission observations are supported by quasi-classical trajectory calculations on a global ab initio potential energy surface. Results show that ∼10% of collisions between H atoms moving with ∼60 kcal/mol energy and HCCH result in transfer of up to 70% of this energy to activate internal degrees of freedom.

  6. Saturated lipids decrease mitofusin 2 leading to endoplasmic reticulum stress activation and insulin resistance in hypothalamic cells.

    PubMed

    Diaz, Brenda; Fuentes-Mera, Lizeth; Tovar, Armando; Montiel, Teresa; Massieu, Lourdes; Martínez-Rodríguez, Herminia Guadalupe; Camacho, Alberto

    2015-11-19

    Endoplasmic reticulum (ER) and mitochondria dysfunction contribute to insulin resistance generation during obesity and diabetes. ER and mitochondria interact through Mitofusin 2 (MTF2), which anchors in the outer mitochondrial and ER membranes regulating energy metabolism. Ablation of MTF2 leads to ER stress activation and insulin resistance. Here we determine whether lipotoxic insult induced by saturated lipids decreases MTF2 expression leading to ER stress response in hypothalamus and its effects on insulin sensitivity using in vitro and in vivo models. We found that lipotoxic stimulation induced by palmitic acid, but not the monounsaturated palmitoleic acid, decreases MTF2 protein levels in hypothalamic mHypoA-CLU192 cells. Also, palmitic acid incubation activates ER stress response evidenced by increase in the protein levels of GRP78/BIP marker at later stage than MTF2 downregulation. Additionally, we found that MTF2 alterations induced by palmitic, but not palmitoleic, stimulation exacerbate insulin resistance in hypothalamic cells. Insulin resistance induced by palmitic acid is prevented by pre-incubation of the anti-inflammatory and the ER stress release reagents, sodium salicylate and 4 phenylbutirate, respectively. Finally, we demonstrated that lipotoxic insult induced by high fat feeding to mice decreases MTF2 proteins levels in arcuate nucleus of hypothalamus. Our data indicate that saturated lipids modulate MTF2 expression in hypothalamus coordinating the ER stress response and the susceptibility to insulin resistance.

  7. Loss of the Capsule Increases the Adherence Activity but Decreases the Virulence of Avibacterium paragallinarum.

    PubMed

    Tu, Tzu-Yi; Hsieh, Ming-Kun; Tan, Duen-Huey; Ou, Shan-Chia; Shien, Jui-Hung; Yen, Ting-Ying; Chang, Poa-Chun

    2015-03-01

    Avibacterium paragallinarum is the causative agent of infectious coryza, an important respiratory disease of chickens. The capsule is an important virulence determinant of many pathogenic bacteria, but the function of the capsule in Av. paragallinarum is not well defined. In this study, acapsular mutants of Av. paragallinarum were constructed by inactivation of the hctA gene using the TargeTron gene knockout system. The acapsular mutants were found to have greater hemagglutination activity than did the wild-type strain. Further, acapsular mutants exhibited an increased ability to adhere to DF-1 cells and to form biofilms on abiotic surfaces. Virulence assays showed that acapsular mutants were less virulent than the wild-type strain. Taken together, these results indicated that loss of capsule increases hemagglutination and adhesion activities but decreases the virulence of Av. paragallinarum. These results could be valuable to further elucidate the function of the capsule and the mechanism of pathogenicity of Av. paragallinarum.

  8. A Decrease in Brain Activation Associated with Driving When Listening to Someone Speak

    PubMed Central

    Just, Marcel Adam; Keller, Timothy A.; Cynkar, Jacquelyn

    2009-01-01

    Behavioral studies have shown that engaging in a secondary task, such as talking on a cellular telephone, disrupts driving performance. This study used functional magnetic resonance imaging (fMRI) to investigate the impact of concurrent auditory language comprehension on the brain activity associated with a simulated driving task. Participants steered a vehicle along a curving virtual road, either undisturbed or while listening to spoken sentences that they judged as true or false. The dual task condition produced a significant deterioration in driving accuracy caused by the processing of the auditory sentences. At the same time, the parietal lobe activation associated with spatial processing in the undisturbed driving task decreased by 37% when participants concurrently listened to sentences. The findings show that language comprehension performed concurrently with driving draws mental resources away from the driving and produces deterioration in driving performance, even when it does not require holding or dialing a phone. PMID:18353285

  9. Hypothermia Increases Tissue Plasminogen Activator Expression and Decreases Post-Operative Intra-Abdominal Adhesion

    PubMed Central

    Lee, Chien-Chang; Wang, Hsuan-Mao; Chou, Tzung-Hsin; Wu, Meng-Che; Hsueh, Kuang-Lung; Chen, Shyr-Chyr

    2016-01-01

    Background Therapeutic hypothermia during operation decreases postoperative intra-abdominal adhesion formation. We sought to determine the most appropriate duration of hypothermia, and whether hypothermia affects the expression of tissue plasminogen activator (tPA). Methods 80 male BALB/c mice weighing 25–30 g are randomized into one of five groups: adhesion model with infusion of 15°C saline for 15 minutes (A); 30 minutes (B); 45 minute (C); adhesion model without infusion of cold saline (D); and sham operation without infusion of cold saline (E). Adhesion scores and tPA levels in the peritoneum fluid levels were analyzed on postoperative days 1, 7, and 14. Results On day 14, the cold saline infusion groups (A, B, and C) had lower adhesion scores than the without infusion of cold saline group (D). However, only group B (cold saline infusion for 30 minutes) had a significantly lower adhesion scores than group D. Also, group B was found to have 3.4 fold, 2.3 fold, and 2.2 fold higher levels of tPA than group D on days 1, 7, and 14 respectively. Conclusions Our results suggest that cold saline infusion for 30 minutes was the optimum duration to decrease postoperative intra-abdominal adhesion formation. The decrease in the adhesion formations could be partly due to an increase in the level of tPA. PMID:27583464

  10. Short photoperiod-induced decrease of histamine H3 receptors facilitates activation of hypothalamic neurons in the Siberian hamster.

    PubMed

    Barrett, P; van den Top, M; Wilson, D; Mercer, J G; Song, C K; Bartness, T J; Morgan, P J; Spanswick, D

    2009-08-01

    Nonhibernating seasonal mammals have adapted to temporal changes in food availability through behavioral and physiological mechanisms to store food and energy during times of predictable plenty and conserve energy during predicted shortage. Little is known, however, of the hypothalamic neuronal events that lead to a change in behavior or physiology. Here we show for the first time that a shift from long summer-like to short winter-like photoperiod, which induces physiological adaptation to winter in the Siberian hamster, including a body weight decrease of up to 30%, increases neuronal activity in the dorsomedial region of the arcuate nucleus (dmpARC) assessed by electrophysiological patch-clamping recording. Increased neuronal activity in short days is dependent on a photoperiod-driven down-regulation of H3 receptor expression and can be mimicked in long-day dmpARC neurons by the application of the H3 receptor antagonist, clobenproprit. Short-day activation of dmpARC neurons results in increased c-Fos expression. Tract tracing with the trans-synaptic retrograde tracer, pseudorabies virus, delivered into adipose tissue reveals a multisynaptic neuronal sympathetic outflow from dmpARC to white adipose tissue. These data strongly suggest that increased activity of dmpARC neurons, as a consequence of down-regulation of the histamine H3 receptor, contributes to the physiological adaptation of body weight regulation in seasonal photoperiod.

  11. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    SciTech Connect

    Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  12. Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity.

    PubMed

    Yu, Jinghua; Lo, Jane-L; Huang, Li; Zhao, Annie; Metzger, Edward; Adams, Alan; Meinke, Peter T; Wright, Samuel D; Cui, Jisong

    2002-08-30

    Bile salt export pump (BSEP) is a major bile acid transporter in the liver. Mutations in BSEP result in progressive intrahepatic cholestasis, a severe liver disease that impairs bile flow and causes irreversible liver damage. BSEP is a target for inhibition and down-regulation by drugs and abnormal bile salt metabolites, and such inhibition and down-regulation may result in bile acid retention and intrahepatic cholestasis. In this study, we quantitatively analyzed the regulation of BSEP expression by FXR ligands in primary human hepatocytes and HepG2 cells. We demonstrate that BSEP expression is dramatically regulated by ligands of the nuclear receptor farnesoid X receptor (FXR). Both the endogenous FXR agonist chenodeoxycholate (CDCA) and synthetic FXR ligand GW4064 effectively increased BSEP mRNA in both cell types. This up-regulation was readily detectable at as early as 3 h, and the ligand potency for BSEP regulation correlates with the intrinsic activity on FXR. These results suggest BSEP as a direct target of FXR and support the recent report that the BSEP promoter is transactivated by FXR. In contrast to CDCA and GW4064, lithocholate (LCA), a hydrophobic bile acid and a potent inducer of cholestasis, strongly decreased BSEP expression. Previous studies did not identify LCA as an FXR antagonist ligand in cells, but we show here that LCA is an FXR antagonist with partial agonist activity in cells. In an in vitro co-activator association assay, LCA decreased CDCA- and GW4064-induced FXR activation with an IC(50) of 1 microm. In HepG2 cells, LCA also effectively antagonized GW4064-enhanced FXR transactivation. These data suggest that the toxic and cholestatic effect of LCA in animals may result from its down-regulation of BSEP through FXR. Taken together, these observations indicate that FXR plays an important role in BSEP gene expression and that FXR ligands may be potential therapeutic drugs for intrahepatic cholestasis.

  13. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    SciTech Connect

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W. )

    1991-03-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions.

  14. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    PubMed Central

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  15. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

    PubMed

    Bai, Xiyuan; Feldman, Nicole E; Chmura, Kathryn; Ovrutsky, Alida R; Su, Wen-Lin; Griffin, Laura; Pyeon, Dohun; McGibney, Mischa T; Strand, Matthew J; Numata, Mari; Murakami, Seiji; Gaido, Loretta; Honda, Jennifer R; Kinney, William H; Oberley-Deegan, Rebecca E; Voelker, Dennis R; Ordway, Diane J; Chan, Edward D

    2013-01-01

    Nuclear factor-kappa B (NFκB) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB). However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase) or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

  16. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

    PubMed

    Bai, Xiyuan; Feldman, Nicole E; Chmura, Kathryn; Ovrutsky, Alida R; Su, Wen-Lin; Griffin, Laura; Pyeon, Dohun; McGibney, Mischa T; Strand, Matthew J; Numata, Mari; Murakami, Seiji; Gaido, Loretta; Honda, Jennifer R; Kinney, William H; Oberley-Deegan, Rebecca E; Voelker, Dennis R; Ordway, Diane J; Chan, Edward D

    2013-01-01

    Nuclear factor-kappa B (NFκB) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB). However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase) or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy. PMID:23634218

  17. Inhibition of Nuclear Factor-Kappa B Activation Decreases Survival of Mycobacterium tuberculosis in Human Macrophages

    PubMed Central

    Chmura, Kathryn; Ovrutsky, Alida R.; Su, Wen-Lin; Griffin, Laura; Pyeon, Dohun; McGibney, Mischa T.; Strand, Matthew J.; Numata, Mari; Murakami, Seiji; Gaido, Loretta; Honda, Jennifer R.; Kinney, William H.; Oberley-Deegan, Rebecca E.; Voelker, Dennis R.; Ordway, Diane J.; Chan, Edward D.

    2013-01-01

    Nuclear factor-kappa B (NFκB) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB). However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase) or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy. PMID:23634218

  18. Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart.

    PubMed

    O'Tierney, P F; Anderson, D F; Faber, J J; Louey, S; Thornburg, K L; Giraud, G D

    2010-08-01

    The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 +/- 2.8 mmHg) was lower than that of control fetuses (47.5 +/- 4.7 mmHg) (P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 +/- 0.5 g/kg vs. 7.0 +/- 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle (P < 0.005) and the left ventricle (P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart. PMID:20484695

  19. Decreased resting-state brain activity complexity in schizophrenia characterized by both increased regularity and randomness.

    PubMed

    Yang, Albert C; Hong, Chen-Jee; Liou, Yin-Jay; Huang, Kai-Lin; Huang, Chu-Chung; Liu, Mu-En; Lo, Men-Tzung; Huang, Norden E; Peng, Chung-Kang; Lin, Ching-Po; Tsai, Shih-Jen

    2015-06-01

    Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 age- and sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia.

  20. Activated carbon decreases invasive plant growth by mediating plant-microbe interactions.

    PubMed

    Nolan, Nicole E; Kulmatiski, Andrew; Beard, Karen H; Norton, Jeanette M

    2014-01-01

    There is growing appreciation for the idea that plant-soil interactions (e.g. allelopathy and plant-microbe feedbacks) may explain the success of some non-native plants. Where this is the case, native plant restoration may require management tools that change plant-soil interactions. Activated carbon (AC) is one such potential tool. Previous research has shown the potential for high concentrations of AC to restore native plant growth to areas dominated by non-natives on a small scale (1 m × 1 m plots). Here we (i) test the efficacy of different AC concentrations at a larger scale (15 m × 15 m plots), (ii) measure microbial responses to AC treatment and (iii) use a greenhouse experiment to identify the primary mechanism, allelopathy versus microbial changes, through which AC impacts native and non-native plant growth. Three years after large-scale applications, AC treatments decreased non-native plant cover and increased the ratio of native to non-native species cover, particularly at concentrations >400 g m(-2). Activated carbon similarly decreased non-native plant growth in the greenhouse. This effect, however, was only observed in live soils, suggesting that AC effects were microbially mediated and not caused by direct allelopathy. Bacterial community analysis of field soils indicated that AC increased the relative abundance of an unidentified bacterium and an Actinomycetales and decreased the relative abundance of a Flavobacterium, suggesting that these organisms may play a role in AC effects on plant growth. Results support the idea that manipulations of plant-microbe interactions may provide novel and effective ways of directing plant growth and community development (e.g. native plant restoration). PMID:25387751

  1. Activated carbon decreases invasive plant growth by mediating plant–microbe interactions

    PubMed Central

    Nolan, Nicole E.; Kulmatiski, Andrew; Beard, Karen H.; Norton, Jeanette M.

    2015-01-01

    There is growing appreciation for the idea that plant–soil interactions (e.g. allelopathy and plant–microbe feedbacks) may explain the success of some non-native plants. Where this is the case, native plant restoration may require management tools that change plant–soil interactions. Activated carbon (AC) is one such potential tool. Previous research has shown the potential for high concentrations of AC to restore native plant growth to areas dominated by non-natives on a small scale (1 m × 1 m plots). Here we (i) test the efficacy of different AC concentrations at a larger scale (15 m × 15 m plots), (ii) measure microbial responses to AC treatment and (iii) use a greenhouse experiment to identify the primary mechanism, allelopathy versus microbial changes, through which AC impacts native and non-native plant growth. Three years after large-scale applications, AC treatments decreased non-native plant cover and increased the ratio of native to non-native species cover, particularly at concentrations >400 g m−2. Activated carbon similarly decreased non-native plant growth in the greenhouse. This effect, however, was only observed in live soils, suggesting that AC effects were microbially mediated and not caused by direct allelopathy. Bacterial community analysis of field soils indicated that AC increased the relative abundance of an unidentified bacterium and an Actinomycetales and decreased the relative abundance of a Flavobacterium, suggesting that these organisms may play a role in AC effects on plant growth. Results support the idea that manipulations of plant–microbe interactions may provide novel and effective ways of directing plant growth and community development (e.g. native plant restoration). PMID:25387751

  2. Pyruvate dehydrogenase activity and quantity decreases after coronary artery bypass grafting: a prospective observational study

    PubMed Central

    Andersen, Lars W.; Liu, Xiaowen; Peng, Teng J.; Giberson, Tyler A.; Khabbaz, Kamal R.; Donnino, Michael W.

    2014-01-01

    Introduction Pyruvate dehydrogenase (PDH) is a key gatekeeper enzyme in aerobic metabolism. The main purpose of this study was to determine if PDH activity is affected by major stress in the form of coronary artery bypass grafting (CABG) which has previously been used as a model of critical illness. Methods We conducted a prospective, observational study of patients undergoing CABG at an urban, tertiary care hospital. We included adult patients undergoing CABG with or without concomitant valve surgery. Measurements of PDH activity and quantity and thiamine were obtained prior to surgery, at the completion of surgery, and 6 hours post-surgery. Results Fourteen patients were enrolled (age: 67 ± 10 years, 21 % female). Study subjects had a mean 41.7 % (SD: 27.7) reduction in PDH activity after surgery and a mean 32.0% (SD: 31.4) reduction 6 hours after surgery (p < 0.001). Eight patients were thiamine deficient (≤ 7 nmol/L) after surgery compared to none prior to surgery (p = 0.002). Thiamine level was a significantly associated with PDH quantity at all time points (p = 0.01). Post-surgery lactate levels were inversely correlated with post-surgery thiamine levels (r = −0.58 and p = 0.04). Conclusion The stress of major surgery causes decreased PDH activity and quantity, and depletion of thiamine levels. PMID:25526377

  3. AMPK over-activation leads to accumulation of α-synuclein oligomers and decrease of neurites

    PubMed Central

    Jiang, Peizhou; Gan, Ming; Ebrahim, Abdul Shukkur; Castanedes-Casey, Monica; Dickson, Dennis W.; Yen, Shu-Hui C.

    2012-01-01

    Neuronal inclusions of α-synuclein (α-syn), termed Lewy bodies, are a hallmark of Parkinson disease (PD). Increased α-syn levels can occur in brains of aging human and neurotoxin treated mice. Since previous studies have shown increased brain lactate levels in aging brains, in PD affected subjects when compared to age-matched controls, and in mice treated with MPTP, we tested the effects of lactate exposure on α-syn in a cell based-study. We demonstrated that (i) lactate treatment led to α-syn accumulation and oligomerization in a time- and concentration-dependent manner, (ii) such alterations were mediated via adenosine-monophosphate activated protein kinase (AMPK) and associated with increasing cytoplasmic phosphorylated AMPK levels, (iii) AMPK activation facilitated α-syn accumulation and phosphorylation, (iv) lactate treatment or overexpression of active form of AMPK decreased α-syn turnover and neurite outgrowth and (v) Lewy body-bearing neurons displayed abnormal cytoplasmic distribution of phosphorylated AMPK, which normally is located in nuclei. Together, our results suggest that chronic neuronal accumulation of α-syn induced by lactate-triggered AMPK activation in aging brains may be a novel mechanism underlying α-synucleionpathies in PD and related disorders. PMID:23200460

  4. CB1 receptor deficiency decreases wheel-running activity: consequences on emotional behaviours and hippocampal neurogenesis.

    PubMed

    Dubreucq, Sarah; Koehl, Muriel; Abrous, Djoher N; Marsicano, Giovanni; Chaouloff, Francis

    2010-07-01

    Chronic voluntary wheel-running activity has been reported to hypersensitise central CB1 receptors in mice. On the other hand, pharmacological findings suggest that the CB1 receptor could be involved in wheel-running behaviour and in running-induced neurogenesis in the hippocampus. We analysed wheel-running behaviour for 6 weeks and measured its consequences on hippocampal neurogenesis in CB1 knockout (CB1(-/-)) animals, compared to wild-type (CB1(+/+)) littermates. Because wheel running has been shown to affect locomotor reactivity in novel environments, memory for aversive events and depression-like behaviours, we also assessed these behaviours in control and running CB1(+/+) and CB1(-/-) mice. When compared with running CB1(+/+) mice, the distance covered weekly by CB1(-/-) mice was decreased by 30-40%, an observation accounted for by decreased time spent and maximal velocity on the wheels. Analyses of running distances with respect to the light/dark cycle revealed that mutant covered less distance throughout both the inactive and the active phases of that cycle. Locomotion in an activity cage, exploration in an open field, and immobility time in the forced swim test proved insensitive to chronic wheel running in either genotype. Wheel running, per se, did not influence the expression and extinction of cued fear memory but counteracted in a time-dependent manner the deficiency of extinction measured in CB1(-/-) mice. Hippocampal neurogenesis, assessed by doublecortin labelling of immature neurons in the dentate gyrus, was lowered by 40% in control CB1(-/-) mice, compared to control CB1(+/+) mice. Although CB1(-/-) mice ran less than their wild-type littermates, the 6-week running protocol increased neurogenesis to similar extents (37-39%) in both genotypes. This study suggests that mouse CB1 receptors control wheel running but not its neurogenic consequences in the hippocampus.

  5. Age-related decrease in physical activity and functional fitness among elderly men and women

    PubMed Central

    Milanović, Zoran; Pantelić, Saša; Trajković, Nebojša; Sporiš, Goran; Kostić, Radmila; James, Nic

    2013-01-01

    Aim To determine differences in physical activity level and functional fitness between young elderly (60–69 years) and old elderly (70–80 years) people with the hypothesis that an age-related decline would be found. Methods A total of 1288 participants’ level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Results Significant differences (P < 0.05) were found for all Senior Fitness tests between young elderly (60–69 years) and old elderly (70–80) men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05). Conclusions This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance. PMID:23723694

  6. Thyrotrophin-releasing hormone decreases feeding and increases body temperature, activity and oxygen consumption in Siberian hamsters.

    PubMed

    Schuhler, S; Warner, A; Finney, N; Bennett, G W; Ebling, F J P; Brameld, J M

    2007-04-01

    Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5-50 mg/kg body weight; i.p.) and central (0.5 microg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function.

  7. PGE2 decreases reactivity of human platelets by activating EP2 and EP4

    PubMed Central

    Smith, James P.; Haddad, Elias V.; Downey, Jason D.; Breyer, Richard M.; Boutaud, O.

    2010-01-01

    Introduction: Platelet hyperreactivity associates with cardiovascular events in humans. Studies in mice and humans suggest that prostaglandin E2 (PGE2) regulates platelet activation. In mice, activation of the PGE2 receptor subtype 3 (EP3) promotes thrombosis, but the significance of EP3 in humans is less well understood. Objectives: To characterize the regulation of thromboxane-dependent human platelet activation by PGE2. Patients/Methods: Platelets collected from nineteen healthy adults were studied using an agonist of the thromboxane receptor (U46,619), PGE2, and selective agonists and/or antagonists of the EP receptor subtypes. Platelet activation was assayed by (1) optical aggregometry, (2) measurement of dense granule release, and (3) single-platelet counting. Results: Healthy volunteers demonstrated significant interindividual variation in platelet response to PGE2. PGE2 completely inhibited U46,619-induced platelet aggregation and ATP release in 26% of subjects; the remaining 74% had partial or no response to PGE2. Antagonism of EP4 abolished the inhibitory effect of PGE2. In all volunteers, a selective EP2 agonist inhibited U46,619-induced aggregation. Furthermore, the selective EP3 antagonist DG-041 converted all PGE2 nonresponders to full responders. Conclusions: There is significant interindividual variation of platelet response to PGE2 in humans. The balance between EP2, EP3, and EP4 activation determines its net effect. PGE2 can prevent thromboxane-induced platelet aggregation in an EP4-dependent manner. EP3 antagonism converts platelets of nonresponders to a PGE2-responsive phenotype. These data suggest that therapeutic targeting of EP pathways may have cardiovascular benefit by decreasing platelet reactivity. PMID:20451959

  8. Ankyrin domain of myosin 16 influences motor function and decreases protein phosphatase catalytic activity.

    PubMed

    Kengyel, András; Bécsi, Bálint; Kónya, Zoltán; Sellers, James R; Erdődi, Ferenc; Nyitrai, Miklós

    2015-05-01

    The unconventional myosin 16 (Myo16), which may have a role in regulation of cell cycle and cell proliferation, can be found in both the nucleus and the cytoplasm. It has a unique, eight ankyrin repeat containing pre-motor domain, the so-called ankyrin domain (My16Ank). Ankyrin repeats are present in several other proteins, e.g., in the regulatory subunit (MYPT1) of the myosin phosphatase holoenzyme, which binds to the protein phosphatase-1 catalytic subunit (PP1c). My16Ank shows sequence similarity to MYPT1. In this work, the interactions of recombinant and isolated My16Ank were examined in vitro. To test the effects of My16Ank on myosin motor function, we used skeletal muscle myosin or nonmuscle myosin 2B. The results showed that My16Ank bound to skeletal muscle myosin (K D ≈ 2.4 µM) and the actin-activated ATPase activity of heavy meromyosin (HMM) was increased in the presence of My16Ank, suggesting that the ankyrin domain can modulate myosin motor activity. My16Ank showed no direct interaction with either globular or filamentous actin. We found, using a surface plasmon resonance-based binding technique, that My16Ank bound to PP1cα (K D ≈ 540 nM) and also to PP1cδ (K D ≈ 600 nM) and decreased its phosphatase activity towards the phosphorylated myosin regulatory light chain. Our results suggest that one function of the ankyrin domain is probably to regulate the function of Myo16. It may influence the motor activity, and in complex with the PP1c isoforms, it can play an important role in the targeted dephosphorylation of certain, as yet unidentified, intracellular proteins.

  9. Observed and projected decrease in Northern Hemisphere extratropical cyclone activity in summer and its impacts on maximum temperature

    NASA Astrophysics Data System (ADS)

    Chang, Edmund K. M.; Ma, Chen-Geng; Zheng, Cheng; Yau, Albert M. W.

    2016-03-01

    Extratropical cyclones cause much of the high-impact weather over the midlatitudes. With increasing greenhouse gases, enhanced high-latitude warming will lead to weaker cyclone activity. Here we show that between 1979 and 2014, the number of strong cyclones in Northern Hemisphere in summer has decreased at a rate of 4% per decade, with even larger decrease found near northeastern North America. Climate models project a decrease in summer cyclone activity, but the observed decreasing rate is near the fastest projected. Decrease in summer cyclone activity will lead to decrease in cloud cover, giving rise to higher maximum temperature, potentially enhancing the increase in maximum temperature by 0.5 K or more over some regions. We also show that climate models may have biases in simulating the positive relationship between cyclone activity and cloud cover, potentially underestimating the impacts of cyclone decrease on accentuating the future increase in maximum temperature.

  10. Impaired ALDH2 activity decreases the mitochondrial respiration in H9C2 cardiomyocytes.

    PubMed

    Mali, Vishal R; Deshpande, Mandar; Pan, Guodong; Thandavarayan, Rajarajan A; Palaniyandi, Suresh S

    2016-02-01

    Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Aldehyde dehydrogenase (ALDH) superfamily contains NAD(P)(+)-dependent isozymes which can detoxify endogenous and exogenous aldehydes into non-toxic carboxylic acids. Therefore we hypothesize that 4HNE afflicts mitochondrial respiration and leads to cell death by impairing ALDH2 activity in cultured H9C2 cardiomyocyte cell lines. H9C2 cardiomyocytes were treated with 25, 50 and 75 μM 4HNE and its vehicle, ethanol as well as 25, 50 and 75 μM disulfiram (DSF), an inhibitor of ALDH2 and its vehicle (DMSO) for 4 h. 4HNE significantly decreased ALDH2 activity, ALDH2 protein levels, mitochondrial respiration and mitochondrial respiratory reserve capacity, and increased 4HNE adduct formation and cell death in cultured H9C2 cardiomyocytes. ALDH2 inhibition by DSF and ALDH2 siRNA attenuated ALDH2 activity besides reducing ALDH2 levels, mitochondrial respiration and mitochondrial respiratory reserve capacity and increased cell death. Our results indicate that ALDH2 impairment can lead to poor mitochondrial respiration and increased cell death in cultured H9C2 cardiomyocytes.

  11. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    PubMed

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients. PMID:24339807

  12. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    SciTech Connect

    Liu, Chun; Ge, Beihai; He, Chao; Zhang, Yi; Liu, Xiaowen; Liu, Kejian; Qian, Cuiping; Zhang, Yu; Peng, Wenzhong; Guo, Xiaomei

    2014-07-18

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.

  13. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    PubMed

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  14. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    PubMed Central

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer’s patients. PMID:24339807

  15. Metabolic adaptation to decreases in energy intake due to changes in the energy cost of low energy expenditure regimen.

    PubMed

    Garby, L

    1990-01-01

    (1) The energy content in food is used in the human body for three main purposes. The first is to maintain the dissipative structures. Most of the structures of the body are of this kind, i.e. they represent stationary non-equilibrium states, or (generalized) stationary potentials, and are inherently unstable. The second is to maintain a body temperature independent of and usually higher than that of the surroundings. The third is to provide energy for performance of external work. The functional structure of the system providing these results consists of a large number of coupled processes (chemical reactions and translocations), in series and in parallel, whose general nature is well understood but whose quantitative extents are mainly unknown. The coupled processes are driven by the spontaneous reaction of the main substrates with oxygen. Energy flows through the system and is converted to heat (and external work) with simultaneous creation of stationary generalized potentials. For each potential there is an associated flow of energy and the relation between the two is an expression of the efficiency with which the potential is maintained. The processes giving rise to the potentials are likely to be controlled with respect to the efficiency with which the potentials are maintained. The control is partly provided through feedback from the potentials themselves: the potentials are regulated. In this way, the system can respond in a non-linear fashion to perturbations in the energy intake (or energy expenditure): the potentials are maintained at constant, or nearly constant, values. The concept of metabolic adaptation implies that control of the efficiency by feedback from the potentials is an important element in the overall regulation of the potentials, including that of the body temperature. (2) The concept of metabolic adaptation can be framed in such a way that it becomes operational. Quantities such as maintained potentials and efficiency can be revealed in

  16. Capsaicin increases sensation of fullness in energy balance, and decreases desire to eat after dinner in negative energy balance.

    PubMed

    Janssens, Pilou L H R; Hursel, Rick; Westerterp-Plantenga, Margriet S

    2014-06-01

    Addition of capsaicin (CAPS) to the diet has been shown to increase satiety; therefore, CAPS is of interest for anti-obesity therapy. We investigated the effects of CAPS on appetite profile and ad libitum energy intake in relation to energy balance. Fifteen subjects (seven women and eight men, age: 29.7 ± 10.8yrs, BMI: 23.3 ± 2.9 kg/m(2)) underwent four conditions in a randomized crossover design in 36 hour sessions in a respiration chamber; they received 100% of their daily energy requirements in the conditions "100%Control" and "100%CAPS", and 75% of their daily energy requirements in the conditions "75%Control" and "75%CAPS", followed by an ad libitum dinner. In the 100%CAPS and 75%CAPS conditions, CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units) with every meal. Satiety (P < 0.05) and fullness (P = 0.01) were measured every waking hour and before and after every meal using visual analogue scales, and were higher in the 100%CAPS versus 100%Control condition. After dinner desire to eat, satiety and fullness did not differ between 75%CAPS and 100%Control, while desire to eat was higher (P < 0.05) and satiety (P = 0.06) and fullness (P = 0.06) tended to be lower in the 75%Control versus 100%Control condition. Furthermore, ad libitum intake (P = 0.07) and overconsumption (P = 0.06) tended to decrease in 100%CAPS versus 100%Control. In energy balance, addition of capsaicin to the diet increases satiety and fullness, and tends to prevent overeating when food intake is ad libitum. After dinner, capsaicin prevents the effects of the negative energy balance on desire to eat.

  17. Microglial activation decreases retention of the protease inhibitor saquinavir: implications for HIV treatment

    PubMed Central

    2013-01-01

    Background Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide. Methods To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent microglia exposed to the prototypical inflammatory mediator lipopolysaccharide (LPS). Results [3H]-Saquinavir accumulation by microglia was rapid, and was increased up to two-fold in the presence of the specific P-glycoprotein inhibitor, PSC833. After six or 24 hours of exposure to 10 ng/ml LPS, saquinavir accumulation was decreased by up to 45%. LPS did not directly inhibit saquinavir transport, and did not affect P-glycoprotein protein expression. LPS exposure did not alter RNA and/or protein expression of other transporters including multidrug resistance-associated protein 1 and several solute carrier uptake transporters. Conclusions The decrease in saquinavir accumulation in microglia following treatment with LPS is likely multi-factorial, since drug accumulation was attenuated by inhibitors of NF-κβ and the MEK1/2 pathway in the microglia cell line HAPI, and in primary microglia cultures from toll-like receptor 4 deficient mice. These data provide new pharmacological insights into why microglia act as a difficult-to-treat viral sanctuary site. PMID:23642074

  18. Solar Energy Project, Activities: Biology.

    ERIC Educational Resources Information Center

    Tullock, Bruce, Ed.; And Others

    This guide contains lesson plans and outlines of science activities which present concepts of solar energy in the context of biology experiments. Each unit presents an introduction; objectives; skills and knowledge needed; materials; methods; questions; recommendations for further work; and a teacher information sheet. The teacher information…

  19. Activation energy measurements of cheese

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Temperature sweeps of cheeses using small amplitude oscillatory shear tests produced values for activation energy of flow (Ea) between 30 and 44 deg C. Soft goat cheese and Queso Fresco, which are high-moisture cheeses and do not flow when heated, exhibited Ea values between 30 and 60 kJ/mol. The ...

  20. Plasmonic color filters to decrease ambient light errors on active type dual band infrared image sensors

    NASA Astrophysics Data System (ADS)

    Lyu, Hong-Kun; Park, Young-Jin; Cho, Hui-Sup; Jo, Sung-Hyun; Lee, Hee-Ho; Shin, Jang-Kyoo

    2014-09-01

    In this paper, we proposed the plasmonic color filters to decrease ambient light errors on active type dual band infrared image sensors for a large-area multi-touch display system. Although the strong point of the touch display system in the area of education and exhibition there are some limits of the ambient light. When an unexpected ambient light incidents into the display the touch recognition system can make errors classifying the touch point in the unexpected ambient light area. We proposed a new touch recognition image sensor system to decrease the ambient light error and investigated the optical transmission properties of plasmonic color filters for IR image sensor. To find a proper structure of the plasmonic color filters we used a commercial computer simulation tool utilizing finite-difference time-domain (FDTD) method as several thicknesses and whit the cover passivation layer or not. Gold (Au) applied for the metal film and the dispersion information associated with was derived from the Lorentz-Drude model. We also described the mechanism applied the double band filter on the IR image sensors.

  1. BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

    PubMed

    Klenke, Ulrike; Constantin, Stephanie; Wray, Susan

    2016-05-01

    Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50μM BPA significantly decreased GnRH calcium activity. Blockage of γ-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-β, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-γ, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA-mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-γ, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons. PMID:26934298

  2. BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

    PubMed

    Klenke, Ulrike; Constantin, Stephanie; Wray, Susan

    2016-05-01

    Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50μM BPA significantly decreased GnRH calcium activity. Blockage of γ-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-β, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-γ, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA-mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-γ, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons.

  3. Is Pedometer-Determined Physical Activity Decreasing in Czech Adults? Findings from 2008 to 2013

    PubMed Central

    Pelclová, Jana; Frömel, Karel; Řepka, Emil; Bláha, Ladislav; Suchomel, Aleš; Fojtík, Igor; Feltlová, Dana; Valach, Petr; Horák, Svatopluk; Nykodým, Jiří; Vorlíček, Michal

    2016-01-01

    Objective measured trend data are important for public health practice. However, these data are rare for an adult population. Therefore, the aim of this study was to describe time trends in pedometer-determined physical activity of Czech adults (25–65 years) from 2008 to 2013. Participants were Czech national citizens whose physical activity was assessed objectively using a Yamax Digiwalker SW-700 pedometer (Yamax Corporation, Tokyo, Japan) for seven consecutive days in the period 2008 to 2013. The final sample was 4647 Czech adults [M age 41.4 ± 10 years; M body mass index (BMI) 25.1 ± 3.7 kg/m2]. The results showed that men took more steps/day (M (Mean) = 10,014; 95% CI (Confidence Interval) = 9864–10,164) than women (M = 9448; 95% CI = 9322–9673) in all age and BMI groups. Mean steps/day declined from 2008 to 2013 by 852 steps/day in men and 1491 steps/day in women. In the whole sample, the proportion of participants who had a sedentary lifestyle (<5000 steps/day) increased by 5.8%; the proportion taking ≥10,000 steps/day decreased by 15.8%. In 2013, men and women were 2.67 and 2.05 times, respectively, more likely to have a physically inactive lifestyle (<7500 steps/day) than in 2008. Conversely, in 2008, men and women were 1.68 and 2.46 times, respectively, less likely to have very active lifestyle (>12,500 steps/day). In conclusion, this study suggests that there has been a substantial reduction in physical activity in Czech adults over time. PMID:27783062

  4. Decreased Pregnane X Receptor Expression in Children with Active Crohn’s Disease

    PubMed Central

    Vyhlidal, Carrie; Friesen, Craig; Hildreth, Amber; Singh, Vivekanand; Daniel, James; Kearns, Gregory L.; Leeder, J. Steven

    2016-01-01

    Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn’s disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn’s disease (CD) and 12 age- and sex-matched controls (aged 7–17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed duodenum of children with CD. Relative expression was determined via reverse transcription real-time quantitative polymerase chain reaction, data normalized to glyceraldehyde 3-phosphate dehydrogenase, and differences in gene expression explored via paired t tests. PXR expression was decreased in the inflamed TI versus noninflamed duodenum (TI = 1.88 ± 0.89 versus duodenum = 2.5 ± 0.67; P < 0.001) in CD, but not controls (TI = 2.11 ± 0.41 versus duodenum = 2.26 ± 0.61; P = 0.52). CYP3A4 expression was decreased in CD (TI = –0.89 ± 3.11 versus duodenum = 1.90 ± 2.29; P < 0.05), but not controls (TI = 2.46 ± 0.51 versus duodenum = 2.60 ± 0.60; P = 0.61), as was VIL1 (CD TI = 3.80 ± 0.94 versus duodenum = 4.61 ± 0.52; P < 0.001; controls TI = 4.30 ± 0.35 versus duodenum = 4.47 ± 0.40; P = 0.29). PXR expression correlated with VIL1 (r = 0.78, P = 0.01) and CYP3A4 (r = 0.52, P = 0.01) expression. In conclusion, PXR, CYP3A4, and VIL1 expression was decreased only in the actively inflamed small intestinal tissue in children with CD. Our findings suggest that inflammation has the potential to influence expression of genes, and potentially intestinal proteins, important to drug disposition and response. The observed differential patterns of gene expression support further investigation of the role of PXR in the pathogenesis and/or treatment of pediatric Crohn

  5. Protein-energy malnutrition alters histological and ultrastructural characteristics of the bone marrow and decreases haematopoiesis in adult mice.

    PubMed

    Xavier, J G; Favero, M E; Vinolo, M A R; Rogero, M M; Dagli, M L Z; Arana-Chavez, V E; Borojevic, R; Borelli, P

    2007-06-01

    Protein-energy malnutrition (PEM) decreases resistance to infection by impairing a number of physiological processes, including haematopoiesis. The aim of this study was to evaluate the microanatomical aspects of bone marrow (BM) in mice that were subjected to PEM, in particular, with respect to the components of the local extracellular matrix and the proliferative activity of haematopoietic cells. For this, histological, histochemical, immunohistochemical and ultrastructural techniques were used. Two-month old male Swiss mice were fed with a low-protein diet containing 4% protein and control mice fed a 20% protein diet. When the experimental group had attained a 25% loss of their original body weight, we collected the different biological samples. Malnourished mice had presented severe BM atrophy as well as a reduction in proliferating cell nuclear antigen and gelatinous degeneration. The malnourished mice had more fibronectin accretion in paratrabecular and endosteal regions and more laminin deposition in perisinusal sites than controls. Endosteal cell activation and hyperplasia were found, suggesting their participation in the process. Additionally, we have observed a decrease in the capacity of malnourished haematopoietic stroma to support the growth of haematopoietic stem cells (CD34+) in vitro. These findings point to a structural impairment of the haematopoietic microenvironments in mice with PEM, possibly hampering the interactions between cells and cellular signalling.

  6. Aluminum-induced decrease in CO2 assimilation in citrus seedlings is unaccompanied by decreased activities of key enzymes involved in CO2 assimilation.

    PubMed

    Chen, Li-Song; Qi, Yi-Ping; Smith, Brandon Rhett; Liu, Xing-Hui

    2005-03-01

    'Cleopatra' tangerine (Citrus reshni Hort. ex Tanaka) seedlings were irrigated daily for 8 weeks with 1/4 strength Hoagland's nutrient solution containing 0 (control) or 2 mM aluminum (Al). Leaves from Al-treated plants had decreased CO2 assimilation and stomatal conductance, but increased intercellular CO2 concentrations compared with control leaves. On a leaf area basis, 2 mM Al increased activities of key enzymes in the Calvin cycle, including ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), NADP-glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoribulokinase (PRK), stromal fructose-1,6-bisphosphatase (FBPase), and a key enzyme in starch synthesis, ADP-glucose pyrophosphorylase (AGPase), compared with control leaves. Aluminum had no effect on cytosolic FBPase activity, but it decreased sucrose phosphate synthase (SPS) activity. Aluminum had no effect on area-based concentrations of carbohydrates, glucose-6-phosphate (G6P) and fructose 6-phosphate (F6P) or the G6P:F6P ratio, but it decreased the area-based concentration of 3-phosphoglycerate (PGA). Photochemical quenching coefficient (qP) and electron transport rate through PSII were greatly reduced by Al. Non-photochemical quenching coefficient (NPQ) was less affected by Al than qP and electron transport rate through PSII. We conclude that the reduced rate of CO2 assimilation in Al-treated leaves was probably caused by a combination of factors such as reduced electron transport rate through PSII, increased closure of PSII reaction centers and increased photorespiration.

  7. cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells

    PubMed Central

    Poole, Jill A.; Nordgren, Tara M.; DeVasure, Jane M.; Heires, Art J.; Bailey, Kristina L.; Romberger, Debra J.

    2014-01-01

    Lung injury caused by inhalation of dust from swine-concentrated animal-feeding operations (CAFO) involves the release of inflammatory cytokine interleukin 8 (IL-8), which is mediated by protein kinase C-ε (PKC-ε) in airway epithelial cells. Once activated by CAFO dust, PKC-ε is responsible for slowing cilia beating and reducing cell migration for wound repair. Conversely, the cAMP-dependent protein kinase (PKA) stimulates contrasting effects, such as increased cilia beating and an acceleration of cell migration for wound repair. We hypothesized that a bidirectional mechanism involving PKA and PKC regulates epithelial airway inflammatory responses. To test this hypothesis, primary human bronchial epithelial cells and BEAS-2B cells were treated with hog dust extract (HDE) in the presence or absence of cAMP. PKC-ε activity was significantly reduced in cells that were pretreated for 1 h with 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) before exposure to HDE (P < 0.05). HDE-induced IL-6, and IL-8 release was significantly lower in cells that were pretreated with 8-Br-cAMP (P < 0.05). To exclude exchange protein activated by cAMP (EPAC) involvement, cells were pretreated with either 8-Br-cAMP or 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2Me-cAMP) (EPAC agonist). 8-CPT-2Me-cAMP did not activate PKA and did not reduce HDE-stimulated IL-6 release. In contrast, 8-Br-cAMP decreased HDE-stimulated tumor necrosis factor (TNF)-α-converting enzyme (TACE; ADAM-17) activity and subsequent TNF-α release (P < 0.001). 8-Br-cAMP also blocked HDE-stimulated IL-6 and keratinocyte-derived chemokine release in precision-cut mouse lung slices (P < 0.05). These data show bidirectional regulation of PKC-ε via a PKA-mediated inhibition of TACE activity resulting in reduced PKC-ε-mediated release of IL-6 and IL-8. PMID:25150062

  8. cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells.

    PubMed

    Wyatt, Todd A; Poole, Jill A; Nordgren, Tara M; DeVasure, Jane M; Heires, Art J; Bailey, Kristina L; Romberger, Debra J

    2014-10-15

    Lung injury caused by inhalation of dust from swine-concentrated animal-feeding operations (CAFO) involves the release of inflammatory cytokine interleukin 8 (IL-8), which is mediated by protein kinase C-ε (PKC-ε) in airway epithelial cells. Once activated by CAFO dust, PKC-ε is responsible for slowing cilia beating and reducing cell migration for wound repair. Conversely, the cAMP-dependent protein kinase (PKA) stimulates contrasting effects, such as increased cilia beating and an acceleration of cell migration for wound repair. We hypothesized that a bidirectional mechanism involving PKA and PKC regulates epithelial airway inflammatory responses. To test this hypothesis, primary human bronchial epithelial cells and BEAS-2B cells were treated with hog dust extract (HDE) in the presence or absence of cAMP. PKC-ε activity was significantly reduced in cells that were pretreated for 1 h with 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) before exposure to HDE (P < 0.05). HDE-induced IL-6, and IL-8 release was significantly lower in cells that were pretreated with 8-Br-cAMP (P < 0.05). To exclude exchange protein activated by cAMP (EPAC) involvement, cells were pretreated with either 8-Br-cAMP or 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2Me-cAMP) (EPAC agonist). 8-CPT-2Me-cAMP did not activate PKA and did not reduce HDE-stimulated IL-6 release. In contrast, 8-Br-cAMP decreased HDE-stimulated tumor necrosis factor (TNF)-α-converting enzyme (TACE; ADAM-17) activity and subsequent TNF-α release (P < 0.001). 8-Br-cAMP also blocked HDE-stimulated IL-6 and keratinocyte-derived chemokine release in precision-cut mouse lung slices (P < 0.05). These data show bidirectional regulation of PKC-ε via a PKA-mediated inhibition of TACE activity resulting in reduced PKC-ε-mediated release of IL-6 and IL-8. PMID:25150062

  9. HSP90 inhibitors decrease AID levels and activity in mice and in human cells.

    PubMed

    Montamat-Sicotte, Damien; Litzler, Ludivine C; Abreu, Cecilia; Safavi, Shiva; Zahn, Astrid; Orthwein, Alexandre; Müschen, Markus; Oppezzo, Pablo; Muñoz, Denise P; Di Noia, Javier M

    2015-08-01

    Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert noncanonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications.

  10. Decreasing CNPY2 Expression Diminishes Colorectal Tumor Growth and Development through Activation of p53 Pathway.

    PubMed

    Yan, Ping; Gong, Hui; Zhai, Xiaoyan; Feng, Yi; Wu, Jun; He, Sheng; Guo, Jian; Wang, Xiaoxia; Guo, Rui; Xie, Jun; Li, Ren-Ke

    2016-04-01

    Neovascularization drives tumor development, and angiogenic factors are important neovascularization initiators. We recently identified the secreted angiogenic factor CNPY2, but its involvement in cancer has not been explored. Herein, we investigate CNPY2's role in human colorectal cancer (CRC) development. Tumor samples were obtained from CRC patients undergoing surgery. Canopy 2 (CNPY2) expression was analyzed in tumor and adjacent normal tissue. Stable lines of human HCT116 cells expressing CNPY2 shRNA or control shRNA were established. To determine CNPY2's effects on tumor xenografts in vivo, human CNPY2 shRNA HCT116 cells and controls were injected into nude mice, separately. Cellular apoptosis, growth, and angiogenesis in the xenografts were evaluated. CNPY2 expression was significantly higher in CRC tissues. CNPY2 knockdown in HCT116 cells inhibited growth and migration and promoted apoptosis. In xenografts, CNPY2 knockdown prevented tumor growth and angiogenesis and promoted apoptosis. Knockdown of CNPY2 in the HCT116 CRC cell line reversibly increased p53 activity. The p53 activation increased cyclin-dependent kinase inhibitor p21 and decreased cyclin-dependent kinase 2, thereby inhibiting tumor cell growth, inducing cell apoptosis, and reducing angiogenesis both in vitro and in vivo. CNPY2 may play a critical role in CRC development by enhancing cell proliferation, migration, and angiogenesis and by inhibiting apoptosis through negative regulation of the p53 pathway. Therefore, CNPY2 may represent a novel CRC therapeutic target and prognostic indicator. PMID:26835537

  11. PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1

    SciTech Connect

    Rankin, Sherri L.; Guy, Clifford S.; Mearow, Karen M.

    2009-02-13

    p75NTR is expressed throughout the nervous system and its dysregulation is associated with pathological conditions. We have recently demonstrated a signalling cascade initiated by laminin (LN), which upregulates PTEN and downregulates p75NTR. Here we investigate the mechanism by which PTEN modulates p75NTR. Studies using PTEN mutants show that its protein phosphatase activity directly modulates p75NTR protein expression. Nuclear relocalization of PTEN subsequent to LN stimulation suggests transcriptional control of p75NTR expression, which was confirmed following EMSA and ChIP analysis of Sp1 transcription factor binding activity. LN and PTEN independently decrease the DNA-binding ability of PTEN to the p75NTR promoter. Sp1 regulation of p75NTR occurs via dephosphorylation of Sp1, thus reducing p75NTR transcription and protein expression. This mechanism represents a novel regulatory pathway which controls the expression level of a receptor with broad implications not only for the development of the nervous system but also for progression of pathological conditions.

  12. Hormonal control in a state of decreased activation: potentiation of arginine vasopressin secretion.

    PubMed

    O'Halloran, J P; Jevning, R; Wilson, A F; Skowsky, R; Walsh, R N; Alexander, C

    1985-10-01

    Behaviorally induced stress is associated with increased arginine vasopressin (AVP) secretion. In this report we describe a phasic conditioned response of AVP secretion yielding 2.6-7.1 times normal plasma concentration of this hormone in association with a physiological state of decreased activation, that associated with the mental technique of "transcendental meditation" (TM) in long-term practitioners (6-8 years of regular elicitation). Such a very large phasic response of AVP was previously unknown in the normal physiology of AVP. This elevation was not accompanied by elevation of plasma osmolality. Unstylized ordinary eyes closed rest in a separate group of subjects studied in the same manner was associated with normal plasma AVP concentration. Galvanic skin resistance (GSR) increased during both TM and rest with significantly larger increase associated with TM. Other measures of activation, including muscle metabolism, and the Spielberger Anxiety Inventory indicated marked relaxation in association with TM. In previous research it has been shown that blood pressure does not change acutely during this behavior. These observations indicate that neither stress nor operation of other usual homeostatic control mechanisms are responsible for elevated for AVP in the meditators. It is speculated that the apparently unique mechanism of TM-induced AVP secretion may be more specifically related to the behavioral effects of meditation.

  13. Loss of rostral brainstem cholinergic activity results in decreased ultrasonic vocalization behavior and altered sensorimotor gating.

    PubMed

    Machold, Robert P

    2013-11-01

    The parabigeminal (PBG), pedunculopontine (PPTg), and laterodorsal tegmental (LDTg) nuclei located in the rostral brainstem are the primary sources of the neurotransmitter acetylcholine (ACh) for the midbrain and thalamus, and as part of the ascending reticular activating system, these cholinergic signaling pathways regulate mouse behavioral responses to sensory stimuli. Here, I report that mice harboring a conditional deletion of ACh synthesis specifically within these nuclei (ChAT(En1 KO)) exhibit decreased ultrasonic vocalizations both as pups and adults, consistent with their previously reported hypoactivity when exploring the novel environment of the open field arena. Furthermore, in prepulse inhibition (PPI) tests, ChAT(En1 KO) animals exhibited increased sensorimotor gating in comparison to control littermates. These data suggest that ACh signaling arising from the rostral brainstem modulates animal behavior in part by tuning the levels of sensorimotor gating. Thus, the net effect of this cholinergic activity is to increase sensitivity to environmental stimuli, and loss of this pathway contributes to the hypoactivity in these mutants by raising the sensory threshold for eliciting exploratory behaviors.

  14. Fasciola hepatica Kunitz Type Molecule Decreases Dendritic Cell Activation and Their Ability to Induce Inflammatory Responses

    PubMed Central

    Falcón, Cristian R.; Masih, Diana; Gatti, Gerardo; Sanchez, María Cecilia; Motrán, Claudia C.; Cervi, Laura

    2014-01-01

    The complete repertoire of proteins with immunomodulatory activity in Fasciola hepatica (Fh) has not yet been fully described. Here, we demonstrated that Fh total extract (TE) reduced LPS-induced DC maturation, and the DC ability to induce allogeneic responses. After TE fractionating, a fraction lower than 10 kDa (F<10 kDa) was able to maintain the TE properties to modulate the DC pro- and anti-inflammatory cytokine production induced by LPS. In addition, TE or F<10 kDa treatment decreased the ability of immature DC to stimulate the allogeneic responses and induced a novo allogeneic CD4+CD25+Foxp3+ T cells. In contrast, treatment of DC with T/L or F<10 kDa plus LPS (F<10/L) induced a regulatory IL-27 dependent mechanism that diminished the proliferative and Th1 and Th17 allogeneic responses. Finally, we showed that a Kunitz type molecule (Fh-KTM), present in F<10 kDa, was responsible for suppressing pro-inflammatory cytokine production in LPS-activated DC, by printing tolerogenic features on DC that impaired their ability to induce inflammatory responses. These results suggest a modulatory role for this protein, which may be involved in the immune evasion mechanisms of the parasite. PMID:25486609

  15. HSP90 inhibitors decrease AID levels and activity in mice and in human cells

    PubMed Central

    Montamat-Sicotte, Damien; Liztler, Ludivine C; Abreu, Cecilia; Safavi, Shiva; Zahn, Astrid; Orthwein, Alexandre; Muschen, Markus; Oppezzo, Pablo; Muñoz, Denise P; Di Noia, Javier M

    2015-01-01

    Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert non-canonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications. PMID:25912253

  16. Erythropoietin stimulation decreases hepcidin expression through hematopoietic activity on bone marrow cells in mice.

    PubMed

    Sasaki, Yusuke; Noguchi-Sasaki, Mariko; Yasuno, Hideyuki; Yorozu, Keigo; Shimonaka, Yasushi

    2012-12-01

    Erythropoiesis-stimulating agents (ESA) are now central to the treatment of renal anemia and are associated with improved clinical outcomes. It is well known that erythropoietin (EPO) is a key regulator of erythropoiesis through its promotion of red blood cell production. In order to investigate the role of ESA on iron metabolism, we analyzed the regulation of the iron regulatory hormone hepcidin by ESA treatment in a bone marrow transplant model in mouse. After treating C57BL/6 mice with continuous erythropoietin receptor activator (C.E.R.A.), recombinant human epoetin-β (rhEPO), or recombinant human carbamylated epoetin-β (rhCEPO), we investigated serum hepcidin concentrations and parameters of erythropoiesis. Serum hepcidin concentrations after rhEPO treatment were analyzed in mice subjected to total body irradiation followed by bone marrow transplantation. C.E.R.A. administration caused long-term downregulation of serum hepcidin levels. Serum hepcidin levels in rhEPO-treated mice decreased significantly, whereas there was no change in rhCEPO-treated mice. The reduction in circulating hepcidin levels after rhEPO administration was not observed in irradiated mice. Finally, bone marrow transplantation recovered the response to rhEPO administration that downregulates hepcidin concentration in irradiated mice. These results indicate that ESA treatment downregulates serum hepcidin concentrations, mainly by indirect mechanisms affecting hematopoietic activity in bone marrow cells. PMID:23160767

  17. Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study

    PubMed Central

    Casazza, K; Hanks, LJ; Hidalgo, B; Hu, HH; Affuso, O

    2011-01-01

    Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 minutes of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after ten weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization. PMID:21939791

  18. WAPA Daily Energy Accounting Activities

    1990-10-01

    ISA (Interchange, Scheduling, & Accounting) is the interchange scheduling system used by the DOE Western Area Power Administration to perform energy accounting functions associated with the daily activities of the Watertown Operations Office (WOO). The system's primary role is to provide accounting functions for scheduled energy which is exchanged with other power companies and power operating organizations. The system has a secondary role of providing a historical record of all scheduled interchange transactions. The followingmore » major functions are performed by ISA: scheduled energy accounting for received and delivered energy; generation scheduling accounting for both fossil and hydro-electric power plants; metered energy accounting for received and delivered totals; energy accounting for Direct Current (D.C.) Ties; regulation accounting; automatic generation control set calculations; accounting summaries for Basin, Heartland Consumers Power District, and the Missouri Basin Municipal Power Agency; calculation of estimated generation for the Laramie River Station plant; daily and monthly reports; and dual control areas.« less

  19. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    PubMed

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  20. Decreased expression of mitochondrial aldehyde dehydrogenase-2 induces liver injury via activation of the mitogen-activated protein kinase pathway.

    PubMed

    Zhong, Zibiao; Ye, Shaojun; Xiong, Yan; Wu, Lianxi; Zhang, Meng; Fan, Xiaoli; Li, Ling; Fu, Zhen; Wang, Huanglei; Chen, Mingyun; Yan, Xiaomin; Huang, Wei; Ko, Dicken Shiu-Chung; Wang, Yanfeng; Ye, Qifa

    2016-01-01

    The aim of this study was to determine the role of ALDH2 in the injury of liver from brain-dead donors. Using brain-dead rabbit model and hypoxia model, levels of ALDH2 and apoptosis in tissues and cell lines were determined by Western blot, flow cytometry (FCM), and transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assays. After the expression of ALDH2 during hypoxia had been inhibited or activated, the accumulations of 4-hydroxynonenal (4-HNE) and molecules involved in mitogen-activated protein kinase (MAPK) signaling pathway were analyzed using ELISA kit and Western blot. The low expression of phosphorylated ALDH2 in liver was time-dependent in the brain-dead rabbit model. Immunohistochemistry showed ALDH2 was primarily located in endothelial, and the rates of cell apoptosis in the donation after brain-death (DBD) rabbit groups significantly increased with time. Following the treatment of inhibitor of ALDH2, daidzein, in combination with hypoxia for 8 h, the apoptosis rate and the levels of 4-HNE, P-JNK, and cleaved caspase-3 significantly increased in contrast to that in hypoxic HUVECs; however, they all decreased after treatment with Alda-1 and hypoxia compared with that in hypoxic HUVECs (P < 0.05). Instead, the levels of P-P38, P-ERK, P-JNK, and cleaved caspase-3 decreased and the ratio of bcl-2/bax increased with ad-ALDH2 (10(6) pfu/ml) in combination with hypoxia for 8 h, which significantly alleviated in contrast to that in hypoxic HUVECs. We found low expression of ALDH2 and high rates of apoptosis in the livers of brain-dead donor rabbits. Furthermore, decreased ALDH2 led to apoptosis in HUVECs through MAPK pathway.

  1. Capsaicin increases sensation of fullness in energy balance, and decreases desire to eat after dinner in negative energy balance.

    PubMed

    Janssens, Pilou L H R; Hursel, Rick; Westerterp-Plantenga, Margriet S

    2014-06-01

    Addition of capsaicin (CAPS) to the diet has been shown to increase satiety; therefore, CAPS is of interest for anti-obesity therapy. We investigated the effects of CAPS on appetite profile and ad libitum energy intake in relation to energy balance. Fifteen subjects (seven women and eight men, age: 29.7 ± 10.8yrs, BMI: 23.3 ± 2.9 kg/m(2)) underwent four conditions in a randomized crossover design in 36 hour sessions in a respiration chamber; they received 100% of their daily energy requirements in the conditions "100%Control" and "100%CAPS", and 75% of their daily energy requirements in the conditions "75%Control" and "75%CAPS", followed by an ad libitum dinner. In the 100%CAPS and 75%CAPS conditions, CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units) with every meal. Satiety (P < 0.05) and fullness (P = 0.01) were measured every waking hour and before and after every meal using visual analogue scales, and were higher in the 100%CAPS versus 100%Control condition. After dinner desire to eat, satiety and fullness did not differ between 75%CAPS and 100%Control, while desire to eat was higher (P < 0.05) and satiety (P = 0.06) and fullness (P = 0.06) tended to be lower in the 75%Control versus 100%Control condition. Furthermore, ad libitum intake (P = 0.07) and overconsumption (P = 0.06) tended to decrease in 100%CAPS versus 100%Control. In energy balance, addition of capsaicin to the diet increases satiety and fullness, and tends to prevent overeating when food intake is ad libitum. After dinner, capsaicin prevents the effects of the negative energy balance on desire to eat. PMID:24630935

  2. Muscle activation characteristics of the front leg during baseball swings with timing correction for sudden velocity decrease.

    PubMed

    Ohta, Yoichi; Nakamoto, Hiroki; Ishii, Yasumitsu; Ikudome, Sachi; Takahashi, Kyohei; Shima, Norihiro

    2014-01-01

    This study aimed to clarify the activation characteristics of the vastus lateralis muscle in the front leg during timing correction for a sudden decrease in the velocity of a target during baseball swings. Eleven male collegiate baseball players performed coincident timing tasks that comprised constant velocity of 8 m/s (unchanged) and a sudden decrease in velocity from 8 to 4 m/s (decreased velocity). Electromyography (EMG) revealed that the muscle activation was typically monophasic when responding unchanged conditions. The type of muscle activation during swings in response to decreased velocity condition was both monophasic and biphasic. When biphasic activation appeared in response to decreased velocity, the impact time and the time to peak EMG amplitude were significantly prolonged and the timing error was significantly smaller than that of monophasic activation. However, the EMG onset from the target start was consistent both monophasic and biphasic activation in response to conditions of decreased velocity. In addition, batters with small timing errors in response to decreased velocity were more likely to generate biphasic EMG activation. These findings indicated that timing correction for a sudden decrease in the velocity of an oncoming target is achieved by modifying the muscle activation characteristics of the vastus lateralis muscle of front leg from monophasic to biphasic to delay reaching peak muscle activation and thus prolong impact time. Therefore, the present findings suggests that the extent of timing errors in response to decreased velocity is influenced by the ability to correct muscle activation after its initiation rather than by delaying the initiation timing of muscle activation during baseball swings.

  3. Muscle activation characteristics of the front leg during baseball swings with timing correction for sudden velocity decrease.

    PubMed

    Ohta, Yoichi; Nakamoto, Hiroki; Ishii, Yasumitsu; Ikudome, Sachi; Takahashi, Kyohei; Shima, Norihiro

    2014-01-01

    This study aimed to clarify the activation characteristics of the vastus lateralis muscle in the front leg during timing correction for a sudden decrease in the velocity of a target during baseball swings. Eleven male collegiate baseball players performed coincident timing tasks that comprised constant velocity of 8 m/s (unchanged) and a sudden decrease in velocity from 8 to 4 m/s (decreased velocity). Electromyography (EMG) revealed that the muscle activation was typically monophasic when responding unchanged conditions. The type of muscle activation during swings in response to decreased velocity condition was both monophasic and biphasic. When biphasic activation appeared in response to decreased velocity, the impact time and the time to peak EMG amplitude were significantly prolonged and the timing error was significantly smaller than that of monophasic activation. However, the EMG onset from the target start was consistent both monophasic and biphasic activation in response to conditions of decreased velocity. In addition, batters with small timing errors in response to decreased velocity were more likely to generate biphasic EMG activation. These findings indicated that timing correction for a sudden decrease in the velocity of an oncoming target is achieved by modifying the muscle activation characteristics of the vastus lateralis muscle of front leg from monophasic to biphasic to delay reaching peak muscle activation and thus prolong impact time. Therefore, the present findings suggests that the extent of timing errors in response to decreased velocity is influenced by the ability to correct muscle activation after its initiation rather than by delaying the initiation timing of muscle activation during baseball swings. PMID:25918848

  4. Muscle Activation Characteristics of the Front Leg During Baseball Swings with Timing Correction for Sudden Velocity Decrease

    PubMed Central

    Ohta, Yoichi; Nakamoto, Hiroki; Ishii, Yasumitsu; Ikudome, Sachi; Takahashi, Kyohei; Shima, Norihiro

    2015-01-01

    This study aimed to clarify the activation characteristics of the vastus lateralis muscle in the front leg during timing correction for a sudden decrease in the velocity of a target during baseball swings. Eleven male collegiate baseball players performed coincident timing tasks that comprised constant velocity of 8 m/s (unchanged) and a sudden decrease in velocity from 8 to 4 m/s (decreased velocity). Electromyography (EMG) revealed that the muscle activation was typically monophasic when responding unchanged conditions. The type of muscle activation during swings in response to decreased velocity condition was both monophasic and biphasic. When biphasic activation appeared in response to decreased velocity, the impact time and the time to peak EMG amplitude were significantly prolonged and the timing error was significantly smaller than that of monophasic activation. However, the EMG onset from the target start was consistent both monophasic and biphasic activation in response to conditions of decreased velocity. In addition, batters with small timing errors in response to decreased velocity were more likely to generate biphasic EMG activation. These findings indicated that timing correction for a sudden decrease in the velocity of an oncoming target is achieved by modifying the muscle activation characteristics of the vastus lateralis muscle of front leg from monophasic to biphasic to delay reaching peak muscle activation and thus prolong impact time. Therefore, the present findings suggests that the extent of timing errors in response to decreased velocity is influenced by the ability to correct muscle activation after its initiation rather than by delaying the initiation timing of muscle activation during baseball swings. PMID:25918848

  5. Decreased Circulating T Regulatory Cells in Egyptian Patients with Nonsegmental Vitiligo: Correlation with Disease Activity

    PubMed Central

    Hegab, Doaa Salah; Attia, Mohamed Attia Saad

    2015-01-01

    Background. Vitiligo is an acquired depigmentary skin disorder resulting from autoimmune destruction of melanocytes. Regulatory T cells (Tregs), specifically CD4+CD25+ and Forkhead box P3+ (FoxP3+) Tregs, acquired notable attention because of their role in a variety of autoimmune pathologies. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to vitiligo pathogenesis. Methods. In order to sustain the role of Tregs in pathogenesis and disease activity of vitiligo, surface markers for CD4+CD25+ and FoxP3+ peripheral Tregs were evaluated by flow cytometry in 80 Egyptian patients with nonsegmental vitiligo in addition to 60 healthy control subjects and correlated with clinical findings. Results. Vitiligo patients had significantly decreased numbers of both peripheral CD4+CD25+ and FoxP3+ T cells compared to control subjects (11.49%  ± 8.58% of CD4+ T cells versus 21.20%  ± 3.08%, and 1.09%  ± 0.96% versus 1.44%  ± 0.24%, resp., P < 0.05 for both). Peripheral numbers of CD4+CD25+ and FoxP3+ Tregs correlated negatively with VIDA score. Conclusion. Treg depletion with impaired immune downregulatory function might play a key role in the autoimmune conditions beyond nonsegmental vitiligo particularly in active cases. Effective Treg cell-based immunotherapies might be a future hope for patients with progressive vitiligo. PMID:26788051

  6. Decreased Circulating T Regulatory Cells in Egyptian Patients with Nonsegmental Vitiligo: Correlation with Disease Activity.

    PubMed

    Hegab, Doaa Salah; Attia, Mohamed Attia Saad

    2015-01-01

    Background. Vitiligo is an acquired depigmentary skin disorder resulting from autoimmune destruction of melanocytes. Regulatory T cells (Tregs), specifically CD4(+)CD25(+) and Forkhead box P3(+) (FoxP3(+)) Tregs, acquired notable attention because of their role in a variety of autoimmune pathologies. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to vitiligo pathogenesis. Methods. In order to sustain the role of Tregs in pathogenesis and disease activity of vitiligo, surface markers for CD4(+)CD25(+) and FoxP3(+) peripheral Tregs were evaluated by flow cytometry in 80 Egyptian patients with nonsegmental vitiligo in addition to 60 healthy control subjects and correlated with clinical findings. Results. Vitiligo patients had significantly decreased numbers of both peripheral CD4(+)CD25(+) and FoxP3(+) T cells compared to control subjects (11.49%  ± 8.58% of CD4(+) T cells versus 21.20%  ± 3.08%, and 1.09%  ± 0.96% versus 1.44%  ± 0.24%, resp., P < 0.05 for both). Peripheral numbers of CD4(+)CD25(+) and FoxP3(+) Tregs correlated negatively with VIDA score. Conclusion. Treg depletion with impaired immune downregulatory function might play a key role in the autoimmune conditions beyond nonsegmental vitiligo particularly in active cases. Effective Treg cell-based immunotherapies might be a future hope for patients with progressive vitiligo. PMID:26788051

  7. Greater than predicted decrease in energy expenditure during exercise after body weight loss in obese men.

    PubMed

    Doucet, Eric; Imbeault, Pascal; St-Pierre, Sylvie; Alméras, Natalie; Mauriège, Pascale; Després, Jean-Pierre; Bouchard, Claude; Tremblay, Angelo

    2003-07-01

    This study was performed retrospectively to investigate whether exercise energy expenditure (EE) measured during a standardized treadmill protocol (4.5 km/h at 0% grade) falls below predicted values after body weight loss in obese men. A reference equation was established to predict net exercise EE in a control sample of 83 obese individuals (27 kg/m(2)< or = body mass index <45 kg/m(2)), using age, fat mass and fat-free mass as independent variables. This equation was then used to predict net exercise EE in another group of 11 obese men before and after a 15-week drug-based weight loss programme that was coupled with energy restriction [-2929 kJ/day (-700 kcal/day)]. Body weight and body composition were determined by hydrodensitometry. Net exercise EE, insulin, leptin, 3,3',5-tri-iodothyronine and free thyroxine were measured after an overnight fast at baseline and 2-4 weeks after the end of the programme, when subjects were weight stable. Body weight was significantly reduced (-11%; P <0.01) at the end of the weight loss programme. At baseline, measured net exercise EE was similar to that predicted from the regression equation [19.6 and 19.8 kJ/min (4.69 and 4.74 kcal/min) respectively; not significant]. However, after the end of the intervention, measured net exercise EE was significantly below the predicted value [15.5 and 17.3 kJ/min (3.71 and 4.14 kcal/min) respectively; P <0.01]. The difference between the predicted and the measured fall in net exercise EE was significantly associated with changes in leptin concentration ( r =0.79, P <0.01), even after correction for changes in fat mass and insulin. These observations suggest that net exercise EE falls below predicted values after body weight loss. In addition, this greater than predicted decrease in net exercise EE was associated with changes in leptin. PMID:12617720

  8. Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity

    PubMed Central

    Ji, Gong-Jun; Liao, Wei; Yu, Yang; Miao, Huan-Huan; Feng, Yi-Xuan; Wang, Kai; Feng, Jian-Hua; Zang, Yu-Feng

    2016-01-01

    Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS. PMID:27799898

  9. Modulation of red cell metabolism by states of decreased activation: comparison between states.

    PubMed

    Jevning, R; Wilson, A F; Pirkle, H; Guich, S; Walsh, R N

    1985-11-01

    Marked decline of red cell metabolism has been described during the acute state of decreased activation associated with the stylized mental technique of transcendental meditation (TM) in long-term meditators (5-10 years regular elicitation, TM instructors). It is not known whether unstylized rest is accompanied by a similar effect and it is not known what effector(s) may contribute to red cell metabolic changes in these states. In the present study ordinary, unstylized rest was found to be accompanied by small increase of red cell glycolytic rate. Apparently, either repeated elicitation of TM behavior or some special feature of this practice become associated with new mechanisms of metabolic control than those previously in operation. Although the data of this study do not permit isolation of the precise psychological determinants of this effect, the range of possible physiological effectors can be delimited. Blood pH, PCO2, PO2, and phosphate can be eliminated as significant for red cell metabolic control during both TM and rest, and based upon related studies, several known hormones such as insulin, T3, T4, arginine vasopressin, oxytocin, prolactin and growth hormone can also be eliminated as responsible effector(s).

  10. Active Prompting to Decrease Cell Phone Use and Increase Seat Belt Use While Driving

    PubMed Central

    Clayton, Michael; Helms, Bridgett; Simpson, Cathy

    2006-01-01

    Automobile crashes are the leading cause of death for those aged 3 to 33, with 43,005 (118 per day) Americans killed in 2002 alone. Seat belt use reduces the risk of serious injury in an accident, and refraining from using a cell phone while driving reduces the risk of an accident. Cell phone use while driving increases accident rates, and leads to 2,600 U.S. fatalities each year. An active prompting procedure was employed to increase seat belt use and decrease cell phone use among drivers exiting a university parking lot. A multiple baseline with reversal design was used to evaluate the presentation of two signs: “Please Hang Up, I Care” and “Please Buckle Up, I Care.” The proportion of drivers who complied with the seat belt prompt was high and in line with previous research. The proportion of drivers who hung up their cell phones in response to the prompt was about equal to that of the seat belt prompt. A procedure that reduces cell phone use among automobile drivers is a significant contribution to the behavioral safety literature. PMID:17020214

  11. Experimental evidence of the decrease of kinetic energy of hadrons in passing through atomic nuclei

    NASA Technical Reports Server (NTRS)

    Strugalski, Z.

    1985-01-01

    Hadrons with kinetic energies higher than the pion production threshold lose their kinetic energies monotonically in traversing atomic nuclei, due to the strong interactions in nuclear matter. This phenomenon is a crude analogy to the energy loss of charged particles in their passage through materials. Experimental evidence is presented.

  12. Ovine maternal nutrient restriction from mid to late gestation decreases heptic progesterone inactivating enzyme activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously we have shown increased concentrations of progesterone and decreased liver weight in mid to late pregnant ewes provided a nutrient restricted vs. adequate diet. This alteration in peripheral progesterone could be due to increased synthesis and/or decreased clearance of progesterone. There...

  13. Decrease of physical activity level in adolescents with limb fractures: an accelerometry-based activity monitor study

    PubMed Central

    2011-01-01

    Background Immobilization and associated periods of inactivity can cause osteopenia, the physiological response of the bone to disuse. Mechanical loading plays an essential role in maintaining bone integrity. Skeletal fractures represent one cause of reduction of the physical activity (PA) level in adolescents. The purpose of this study was to quantify the reduction of PA in adolescents with limb fractures during the cast immobilization period compared with healthy controls. Methods Two hundred twenty adolescents were divided into three groups: those with upper limb fractures (50 cases); lower limb fractures (50 cases); and healthy cases (120 cases). Patients and their healthy peers were matched for gender, age, and seasonal assessment of PA. PA level was assessed during cast immobilization by accelerometer. Time spent in PA in each of the different intensity levels - sedentary, light, moderate, and vigorous - was determined for each participant and expressed in minutes and as a percentage of total valid time. Results Reduction in PA during cast immobilization was statistically significant in patients with limb fractures compared to healthy controls. The total PA count (total number of counts/min) was significantly lower in those with upper and lower limb fractures (-30.1% and -62.4%, respectively) compared with healthy controls (p < 0.0001 and p = 0.0003, respectively). Time spent in moderate-to-vigorous PA by patients with upper and lower limb injuries decreased by 36.9% (p = 0.0003) and 76.6% (p < 0.0001), respectively, and vigorous PA was reduced by 41.4% (p = 0.0008) and 84.4% (p < 0.0001), respectively. Conclusions PA measured by accelerometer is a useful and valid tool to assess the decrease of PA level in adolescents with limb fractures. As cast immobilization and reduced PA are known to induce bone mineral loss, this study provides important information to quantify the decrease of skeletal loading in this patient population. The observed reduction of high

  14. Energy Activities for the Primary Classroom. Revised.

    ERIC Educational Resources Information Center

    Tierney, Blue, Comp.

    An energy education program at the primary level should help students to understand the nature and importance of energy, consider different energy sources, learn about energy conservation, prepare for energy related careers, and become energy conscious in other career fields. The activities charts, readings, and experiments provided in this…

  15. Decreasing the singlet-triplet gap for thermally activated delayed fluorescence molecules by structural modification on the donor fragment: First-principles study

    NASA Astrophysics Data System (ADS)

    Fan, Jian-zhong; Lin, Li-li; Wang, Chuan-kui

    2016-05-01

    The small energy gap between singlet excitons (S) and triplet excitons (T) of organic molecules is a dominant condition for high efficient thermally activated delayed fluorescence (TADF). In this study, influence of modification in donor groups of a series of molecules on their geometries, S-T energy gaps, and photophysical properties, is investigated based on first-principles calculations. Investigation shows that, as the electron donating ability is increased, both S-T energy gap and overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are decreased. This work provides strategy for designing high efficient and multi-color TADF devices.

  16. Rapid decrease in active tension generated by C2C12 myotubes after termination of artificial exercise.

    PubMed

    Fujita, Hideaki; Hirano, Minoru; Shimizu, Kazunori; Nagamori, Eiji

    2010-12-01

    We found that the active tension of C2C12 myotubes that had been subjected to artificial exercise for ~10 days decreased rapidly after termination of the artificial exercise. When differentiated C2C12 myotubes were subjected to continuous 1 Hz artificial exercise for ~10 days, the active tension increased to ~4× compared to that before application of the artificial exercise, as reported previously. On termination of artificial exercise, the active tension decreased rapidly, the level reaching that before application of the artificial exercise within 8 h. Concomitant with the decrease in the active tension, an increase in the amount of ubiquitinated proteins was observed. Real time RT-PCR revealed that the expression of several genes associated with atrophy, namely Smc6, Vegfa, Jarid2, Kitl, Cds2, Inmt, Fasn, Neurl, Topors, and Cul2, were also changed after termination of artificial exercise. These results indicate that termination of artificial exercise induced atrophy-like responses of C2C12 myotubes. Here we found that during the decrease in active tension, the sarcomere structure, especially the thin filament structure, decayed rapidly after termination of artificial exercise. On reapplication of the artificial exercise, the active tension was restored rapidly, within 8 h, concomitant with reformation of the sarcomere structure. These results indicate that disassembly of the sarcomere structure may be one of the reasons for the active tension decrease during disuse muscle atrophy.

  17. A Knockout Mutation of a Constitutive GPCR in Tetrahymena Decreases Both G-Protein Activity and Chemoattraction

    PubMed Central

    Lampert, Thomas J.; Coleman, Kevin D.; Hennessey, Todd M.

    2011-01-01

    Although G-protein coupled receptors (GPCRs) are a common element in many chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G-protein activity has yet been shown in any ciliate. To study the possible role for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena Genome database. One of these knockout mutants, called G6, is a complete knockout of a gene that we call GPCR6 (TTHERM_00925490). Based on sequence comparisons, the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p shares highest amino acid sequence homologies to GPCRs from Paramecium and several plants. One of the phenotypes of the G6 mutant is a decreased responsiveness to the depolarizing ions Ba2+ and K+, suggesting a decrease in basal excitability (decrease in Ca2+ channel activity). The other major phenotype of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA) and proteose peptone (PP), two known chemoattractants in Tetrahymena. Using microsomal [35S]GTPγS binding assays, we found that wild-type (CU427) have a prominent basal G-protein activity. This activity is decreased to the same level by pertussis toxin (a G-protein inhibitor), addition of chemoattractants, or the G6 mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it is likely that this gene codes for a constitutively active GPCR in Tetrahymena. We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to decreased excitability in wild-type and longer runs of smooth forward swimming (less interrupted by direction changes) towards the attractant. Therefore, these attractants may work as inverse agonists through the constitutively active Gpcr6p coupled to a pertussis-sensitive G-protein. PMID:22140501

  18. Energy Storage. Teachers Guide. Science Activities in Energy.

    ERIC Educational Resources Information Center

    Jacobs, Mary Lynn, Ed.

    Included in this science activities energy package for students in grades 4-10 are 12 activities related to energy storage. Each activity is outlined on the front and back of a single sheet and is introduced by a key question. Most of the activities can be completed in the classroom with materials readily available in any community. Among the…

  19. Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments

    PubMed Central

    Kearns, Patrick J.; Angell, John H.; Howard, Evan M.; Deegan, Linda A.; Stanley, Rachel H. R.; Bowen, Jennifer L.

    2016-01-01

    Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy. PMID:27666199

  20. Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments

    NASA Astrophysics Data System (ADS)

    Kearns, Patrick J.; Angell, John H.; Howard, Evan M.; Deegan, Linda A.; Stanley, Rachel H. R.; Bowen, Jennifer L.

    2016-09-01

    Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy.

  1. Decrease in serum cortisol during yoga exercise is correlated with alpha wave activation.

    PubMed

    Kamei, T; Toriumi, Y; Kimura, H; Ohno, S; Kumano, H; Kimura, K

    2000-06-01

    We examined changes in brain waves and blood levels of serum cortisol during yoga exercise in 7 yoga instructors and found that alpha waves increased and serum cortisol decreased. These two measures were negatively correlated (r = -.83). Comparison with a control group of nonpractitioners is desirable.

  2. Limitation of dietary copper and zinc decreases superoxide dismutase activity in the onion fly, Delia antiqua.

    PubMed

    Matsuo, T; Ooe, S; Ishikawa, Y

    1997-06-01

    Larvae of the onion fly, Delia antiqua, have lower superoxide dismutase (SOD) activity when they are fed a defined synthetic diet that contains no copper or zinc. SOD activity was rapidly recovered when these larvae were fed onion bulbs. Addition of copper and zinc to the synthetic diet also led to the recovery of SOD activity. Results of an immunoblotting analysis using anti-D. antiqua CuZnSOD mouse monoclonal antibody suggest that this alteration of SOD activity is dependent on the amount of CuZnSOD. PMID:9172377

  3. Energy and power limits for microbial activity

    NASA Astrophysics Data System (ADS)

    LaRowe, D.; Amend, J.

    2014-12-01

    The goal of this presentation is to describe a quantitative framework for determining how energy limits microbial activity, biomass and, ultimately, biogeochemical processes. Although this model can be applied to any environment, its utility is demonstrated in marine sediments, which are an attractive test habitat because they encompass a broad spectrum of energy levels, varying amounts of biomass and are ubiquitous. The potential number of active microbial cells in Arkonas Basin (Baltic Sea) sediments are estimated as a function of depth by quantifying the amount of energy that is available to them and the rate at which it is supplied: power. The amount of power supplied per cubic centimeter of sediment is determined by calculating the Gibbs energy of fermentation and sulfate reduction in combination with the rate of particulate organic carbon, POC, degradation. The Reactive Continuum Model (Boudreau and Ruddick, 1991), RCM, is used to determine the rate at which POC is made available for microbial consumption. The RCM represents POC as containing a range of different types of organic compounds whose ability to be consumed by microorganisms varies as a function of the age of the sediment and on the distribution of compound types that were initially deposited. The sediment age model and RCM parameters determined by (Mogollon et al., 2012) are used. The power available for fermentation and sulfate reduction coupled to H2 and acetate oxidation varies from 10-8 W cm-3 at the sediment water interface to between 10-11 - 10-12 W cm-3 at 3.5 meters below the seafloor, mbsf. Using values of maintenance powers for each of these catabolic activities taken from the literature, the total number of active cells in these sediments similarly decreases from just less than 108 cell cm-3 at the SWI to 4.6 x 104 cells cm-3 at 3.5 mbsf. The number of moles of POC decreases from 2.6 x 10-5 to 9.5 x 10-6, also becoming more recalcitrant with depth. Boudreau, B. P. and Ruddick, B. R

  4. Decreasing Stereotypy in Preschoolers with Autism Spectrum Disorder: The Role of Increased Physical Activity and Function

    ERIC Educational Resources Information Center

    McLaughlin, Constance Ann Hylton

    2010-01-01

    This study used increased physical activity during recess to reduce stereotypy in preschoolers with Autism Spectrum Disorder. Results indicate increasing physical activity can be used as an intervention to reduce automatically maintained stereotypy in preschoolers with ASD. The intervention had a lesser effect on a preschooler whose stereotypy was…

  5. Introduction to Acoustical Energy. Learning Activity.

    ERIC Educational Resources Information Center

    Shackelford, Ray; Johnson, Steve

    1998-01-01

    This technology education activity will allow the students to observe acoustical energy and will put them in a problem-solving situation where they must use the movement of a sound-activated diaphragm to perform another activity. (Author)

  6. Experimental evidence for shallow, slow-moving landslides activated by a decrease in ground temperature

    NASA Astrophysics Data System (ADS)

    Shibasaki, Tatsuya; Matsuura, Sumio; Okamoto, Takashi

    2016-07-01

    In order to understand the trigger mechanism of slow-moving landslides occurring in the early cold season from late autumn to winter, we investigated the effect of temperature on the shear strength of slip surface soils. Displacement-controlled and shear stress-controlled box shear experiments were performed on undisturbed slip zone soils under residual strength conditions. Test results conducted at temperatures from 9 to 25°C showed remarkable shear strength reductions with decreasing temperature. Creep-like slow shear displacements were induced by a decrease in temperature. These temperature-dependent shear behaviors are attributed to the rheological properties of hydrous smectite that dominantly compose the soil material along the failure surface. Our experimental results imply that ground temperature conditions influence slope instability, especially for shallow landslides occurring in smectite-bearing rock areas.

  7. "Split Them!" Smaller Item Sizes of Cookies Lead to a Decrease in Energy Intake in Children

    ERIC Educational Resources Information Center

    Marchiori, David; Waroquier, Laurent; Klein, Olivier

    2012-01-01

    Objective: Examine the influence of altering the size of snack food (ie, small vs large cookies) on short-term energy intake. Methods: First- and sixth-graders (n = 77) participated in a between-subjects experimental design. All participants were offered the same gram weight of cookies during an afternoon tea at their school. For half of the…

  8. Use of ultrasonic energy to decrease the gel strength of waxy crude oil

    SciTech Connect

    Scribner, M.E.

    1991-01-08

    This patent describes improvement in a process for flowing waxy crude oil through a pipe line. The improvement comprises: applying ultrasonic energy to the flowing crude oil prior to or after combining with the crude oil a solution of polymeric wax crystal modifier whereby the gel strength of the crude oil-wax crystal modifier is lowered.

  9. DELTAMETHRIN AND PERMETHRIN DECREASE SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS IN VITRO.

    EPA Science Inventory

    Effects of pyrethroid insecticides on spontaneous electrical activity were investigated in primary cultures of cortical or spinal cord neurons grown on microelectrode arrays. Bicuculline (40 ¿M) was utilized to block fast GABAergic transmission, and concentration-dependent effect...

  10. BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE

    EPA Science Inventory

    Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmac...

  11. Decreased Flight Activity in Culex pipiens (Diptera: Culicidae) Naturally Infected With Culex flavivirus.

    PubMed

    Newman, Christina M; Anderson, Tavis K; Goldberg, Tony L

    2016-01-01

    Insect-specific flaviviruses (ISFVs) commonly infect vectors of mosquito-borne arboviruses. To investigate whether infection with an ISFV might affect mosquito flight behavior, we quantified flight behavior in Culex pipiens L. naturally infected with Culex flavivirus (CxFV). We observed a significant reduction in the scotophase (dark hours) flight activity of CxFV-positive mosquitoes relative to CxFV-negative mosquitoes, but only a marginal reduction in photophase (light hours) flight activity, and no change in the circadian pattern of flight activity. These results suggest that CxFV infection alters the flight activity of naturally infected Cx. pipiens most dramatically when these vectors are likely to be host seeking and may therefore affect the transmission of medically important arboviruses.

  12. Intracellular ATP Decrease Mediates NLRP3 Inflammasome Activation upon Nigericin and Crystal Stimulation.

    PubMed

    Nomura, Johji; So, Alexander; Tamura, Mizuho; Busso, Nathalie

    2015-12-15

    Activation of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome initiates an inflammatory response, which is associated with host defense against pathogens and the progression of chronic inflammatory diseases such as gout and atherosclerosis. The NLRP3 inflammasome mediates caspase-1 activation and subsequent IL-1β processing in response to various stimuli, including extracellular ATP, although the roles of intracellular ATP (iATP) in NLRP3 activation remain unclear. In this study, we found that in activated macrophages artificial reduction of iATP by 2-deoxyglucose, a glycolysis inhibitor, caused mitochondrial membrane depolarization, leading to IL-1β secretion via NLRP3 and caspase-1 activation. Additionally, the NLRP3 activators nigericin and monosodium urate crystals lowered iATP through K(+)- and Ca(2+)-mediated mitochondrial dysfunction, suggesting a feedback loop between iATP loss and lowering of mitochondrial membrane potential. These results demonstrate the fundamental roles of iATP in the maintenance of mitochondrial function and regulation of IL-1β secretion, and they suggest that maintenance of the intracellular ATP pools could be a strategy for countering NLRP3-mediated inflammation. PMID:26546608

  13. Lithium treatment decreases activities of tau kinases in a murine model of senescence.

    PubMed

    Tajes, Marta; Gutierrez-Cuesta, Javier; Folch, Jaume; Ferrer, Isidre; Caballero, Beatriz; Smith, Mark A; Casadesus, Gemma; Camins, Antoni; Pallás, Mercé

    2008-06-01

    Lithium modulates glycogen synthase kinase 3beta (GSK-3beta), a kinase involved in Alzheimer disease-related tau pathology. To investigate mechanisms of aging and the potential therapy of lithium in neurodegenerative disease, we treated senescence-accelerated mouse (SAM)P8 mice, a murine model of senescence, and mice of the control SAMR1 strain with lithium. The treatment reduced hippocampal caspase 3 and calpain activation, indicating that it provides neuroprotection. Lithium also reduced both the levels and activity of GSK-3beta and the activity of cyclin-dependent kinase 5 and reduced hyperphosphorylation of 3 different phosphoepitopes of tau: Ser199, Ser212, and Ser396. In lithium-treated primary cultures of SAMP8 and SAMR1 cerebellar neurons, there was a marked reduction in protease activity mediated by calpain and caspase 3. Both lithium and SB415286, a specific inhibitor of GSK-3beta, reduced apoptosis in vitro. Taken together, these in vivo and in vitro findings of lithium-mediated reductions in GSK-3beta and cyclin-dependent kinase 5 activities, tau phosphorylation, apoptotic activity, and cell death provide a strong rationale for the use of lithium as a potential treatment in neurodegenerative diseases.

  14. Changes in Microbial Extracellular Enzyme Activity Associated with Decreasing Organic Matter Particle Size in a Louisiana Cypress Swamp

    NASA Astrophysics Data System (ADS)

    Vallaire, S.; Jackson, C. R.

    2005-05-01

    Microbial extracellular enzymes are vital to the decomposition of fine particulate organic matter (FPOM) in aquatic systems. However, little is known about variations in the activity of these enzymes with decreasing FPOM size, and even less is known about the importance of these enzymes in the decomposition of FPOM in wetland sediments. Three sediment samples were collected from a Louisiana cypress swamp and sieved into five size ranges, consisting of course particulate organic matter (>1 mm), and four different sizes of FPOM: 0.5-1mm, 0.25-0.5mm, 0.125-0.25mm, and 0.063-0.125mm. For each size range, we assayed the activities of six enzymes involved in lignocellulose decomposition. Activities of beta-glucosidase, beta-xylosidase, cellobiohydrolase, and beta-N-acetylglucosaminidase were strongly correlated with each other, and the activities of all four hydrolytic enzymes began to decrease in activity on FPOM less than 0.5mm. Peroxidase activity was generally low, but peaked on 0.125-0.25mm particles. Phenol oxidase activity was not detected in any samples, regardless of particle size. These results show that changes in microbial enzyme activity occur as FPOM decreases in size, particularly on particles below a 0.25-0.5mm threshold. These changes may reflect differences in both the microbial community and the nature of the FPOM.

  15. Inhibition of prolidase activity by nickel causes decreased growth of proline auxotrophic CHO cells.

    PubMed

    Miltyk, Wojciech; Surazynski, Arkadiusz; Kasprzak, Kazimierz S; Fivash, Matthew J; Buzard, Gregory S; Phang, James M

    2005-04-15

    Occupational exposure to nickel has been epidemiologically linked to increased cancer risk in the respiratory tract. Nickel-induced cell transformation is associated with both genotoxic and epigenetic mechanisms that are poorly understood. Prolidase [E.C.3.4.13.9] is a cytosolic Mn(II)-activated metalloproteinase that specifically hydrolyzes imidodipeptides with C-terminal proline or hydroxyproline and plays an important role in the recycling of proline for protein synthesis and cell growth. Prolidase also provides free proline as substrate for proline oxidase, whose gene is activated by p53 during apoptosis. The inhibition of prolidase activity by nickel has not yet been studied. We first showed that Ni(II) chloride specifically inhibited prolidase activity in CHO-K1 cells in situ. This interpretation was possible because CHO-K1 cells are proline auxotrophs requiring added free proline or proline released from added Gly-Pro by prolidase. In a dose-dependent fashion, Ni(II) inhibited growth on Gly-Pro but did not inhibit growth on proline, thereby showing inhibition of prolidase in situ in the absence of nonspecific toxicity. Studies using cell-free extracts showed that Ni(II) inhibited prolidase activity when present during prolidase activation with Mn(II) or during incubation with Gly-Pro. In kinetic studies, we found that Ni(II) inhibition of prolidase varied with respect to Mn(II) concentration. Analysis of these data suggested that increasing concentrations of Mn(II) stabilized the enzyme protein against Ni(II) inhibition. Because prolidase is an important enzyme in collagen metabolism, inhibition of the enzyme activity by nickel could alter the metabolism of collagen and other matrix proteins, and thereby alter cell-matrix and cell-cell interactions involved in gene expression, genomic stability, cellular differentiation, and cell proliferation. PMID:15696600

  16. Decreased Ventral Striatal Activity with Impulse Control Disorders in Parkinson’s Disease

    PubMed Central

    Rao, Hengyi; Mamikonyan, Eugenia; Detre, John A.; Siderowf, Andrew D.; Stern, Matthew B.; Potenza, Marc N.; Weintraub, Daniel

    2010-01-01

    Purpose A range of impulse control disorders (ICDs) are reported to occur in Parkinson’s disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood. Methods We used both arterial spin labeling (ASL) perfusion fMRI to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART). Results 18 PD patients, either with a diagnosis of one or more ICDs (N=9) or no lifetime ICD history (N=9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum. Conclusion ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs. PMID:20589879

  17. Decreased ventral striatal activity with impulse control disorders in Parkinson's disease.

    PubMed

    Rao, Hengyi; Mamikonyan, Eugenia; Detre, John A; Siderowf, Andrew D; Stern, Matthew B; Potenza, Marc N; Weintraub, Daniel

    2010-08-15

    A range of impulse control disorders (ICDs) are reported to occur in Parkinson's disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood. We used both arterial spin labeling perfusion functional magnetic resonance imaging (fMRI) to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART). Eighteen PD patients, either with a diagnosis of one or more ICDs (N = 9) or no lifetime ICD history (N = 9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum. ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs. PMID:20589879

  18. Activation of NMDA receptors prevents excessive metabolic decrease in hypoxic rat pups.

    PubMed

    Baig, Mirza Shafiulla; Joseph, Vincent

    2006-05-01

    We tested the hypothesis that glutamate NMDA receptors may help maintain metabolic rate and body temperature during acute or chronic hypoxic exposure in newborn rats. We recorded ventilation, metabolism ((.)V(O(2)) -- ((.)V(CO(2)) and rectal temperature, under normoxia, acute hypoxia (30 min -- 12% O(2)), or following 10 days of chronic hypoxia, in 10 days old male and female rats, receiving saline i.p. injection or the NMDA receptor antagonist MK-801. Acute hypoxia decreased rectal temperature and metabolism, and increased ventilation, and (.)V(E)/((.)V(O(2) and (.)V(E)/((.)V(CO(2) to the same extent in males and females. MK-801 injection amplified the metabolic decrease under acute (in males and females) and chronic (in males) hypoxia, prevented the increase of minute ventilation, while (.)V(E)/((.)V(O(2) or (.)V(E)/((.)V(CO(2)remained constant. Hence, NMDA glutamate receptors help to maintain metabolic rate, minute ventilation and body temperature at a determined level in acute (males and females) and chronic hypoxia (males only).

  19. Metabolic control in a state of decreased activation: modulation of red cell metabolism.

    PubMed

    Jevning, R; Wilson, A F; Pirkle, H; O'Halloran, J P; Walsh, R N

    1983-11-01

    Very little is known in depth of the biochemical and physiological changes induced at the cellular level by human behavioral states. For study of the physiology of behavior at this level, the erythrocyte may be useful, because it is readily available and its metabolism and metabolic control are comparatively well understood. In this report we describe a marked decline of red cell glycolytic rate induced by the transcendental meditation technique (TM). This decline was significantly correlated with decreased plasma lactate concentration and with relaxation as indicated by electrodermal response. The occurrence of sleep was not correlated with the metabolic changes. The observed lack of variation of blood pH, blood gases, glucose, and hematocrit in this behavior implies that the decrease of erythrocyte metabolism is not an epiphenomenon of respiratory change or substrate availability. Based upon further measurements indicating persisting alteration of the red blood cell, we suggest the possibility of attachment of a humoral agent(s) to the cell in the mechanism of this effect. This behavioral effect is unique, and the effector(s) responsible may increase our understanding of metabolic control of the erythrocyte and of TM.

  20. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    PubMed Central

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  1. [Molecular Mechanisms of Functional Activity Decreasing of the Skin Cells With Its Aging].

    PubMed

    Khavinson, V Kh; Linkova, N S; Kukanova, E O; Orlova, O A

    2016-01-01

    The article discusses the pool of signaling molecules that regulate the functional activity of the skin cells. Molecules of apoptosis and cells skin aging are p53, p21, p15, Cdk 4/6 and Bcl-2. Inflammation in skin fibroblasts are realized through the cytokines TNF-α, TGF-β, IL-1, ICAM-1, matrix metalloproteinase MMP-1,2,3,9, transcription factor NF-κB and activator protein AP-1. An important role in the aging of skin cells play neuroimmunoendocrine signaling molecules--melatonin, serotonin, skin fibroblast proliferation marker chromogranin A and CD98hc. Age-related changes in the activity of immune cells of the skin is associated with impaired expression of cluster of differentiation of T-lymphocytes (CD3, CD4, CD5, CD8, CD11) and dendritic cells (CD83⁺). These signaling molecules produced by the fibroblasts of the skin, regulate the activity of immune cells involved in the cascade of reactions associated with inflammatory responses, proliferation, apoptosis and cell regeneration. Based on these data nowadays new highly selective approaches to the diagnosis of the skin and the creation of cosmetic agents for the prevention of aging are developed. PMID:27530044

  2. Greater Impulsivity is Associated with Decreased Brain Activation in Obese Women during a Delay Discounting Task

    PubMed Central

    Stoeckel, Luke E.; Murdaugh, Donna L.; Cox, James E.; Cook, Edwin W.; Weller, Rosalyn E.

    2012-01-01

    Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD) or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual’s ‘indifference point’, or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain. PMID:22948956

  3. [Molecular Mechanisms of Functional Activity Decreasing of the Skin Cells With Its Aging].

    PubMed

    Khavinson, V Kh; Linkova, N S; Kukanova, E O; Orlova, O A

    2016-01-01

    The article discusses the pool of signaling molecules that regulate the functional activity of the skin cells. Molecules of apoptosis and cells skin aging are p53, p21, p15, Cdk 4/6 and Bcl-2. Inflammation in skin fibroblasts are realized through the cytokines TNF-α, TGF-β, IL-1, ICAM-1, matrix metalloproteinase MMP-1,2,3,9, transcription factor NF-κB and activator protein AP-1. An important role in the aging of skin cells play neuroimmunoendocrine signaling molecules--melatonin, serotonin, skin fibroblast proliferation marker chromogranin A and CD98hc. Age-related changes in the activity of immune cells of the skin is associated with impaired expression of cluster of differentiation of T-lymphocytes (CD3, CD4, CD5, CD8, CD11) and dendritic cells (CD83⁺). These signaling molecules produced by the fibroblasts of the skin, regulate the activity of immune cells involved in the cascade of reactions associated with inflammatory responses, proliferation, apoptosis and cell regeneration. Based on these data nowadays new highly selective approaches to the diagnosis of the skin and the creation of cosmetic agents for the prevention of aging are developed.

  4. Decreased ventral anterior cingulate cortex activity is associated with reduced social pain during emotional support.

    PubMed

    Onoda, Keiichi; Okamoto, Yasumasa; Nakashima, Ken'ichiro; Nittono, Hiroshi; Ura, Mitsuhiro; Yamawaki, Shigeto

    2009-01-01

    People feel psychological pain when they are excluded, and this pain is often attenuated when emotional support is received. It is therefore likely that a specific neural mechanism underlies the detection of social exclusion. Similarly, specific neural mechanisms may underlie the beneficial effects of emotional support. Although neuroimaging researchers have recently examined the neural basis of social pain, there is presently no agreement as to which part of the anterior cingulate cortex (ACC) is involved in the perception and modulation of social pain. We hypothesized that activity in those brain regions that are associated with social pain would be correlated with decrements in social pain induced by emotional support. To examine the effects of emotional support on social pain caused by exclusion, we conducted an fMRI study in which participants played a virtual ball-tossing game. Participants were initially included and later excluded from the game. In the latter half of the session from which participants were excluded, participants received emotionally supportive text messages. We found that emotional support led to increased activity in the left lateral/medial prefrontal cortices and some temporal regions. Those individuals who experienced greater attenuation of social pain exhibited lower ventral ACC and higher left lateral prefrontal cortex activation. These results suggest that the ventral ACC underlies social pain, and that emotional support enhances prefrontal cortex activity, which in turn may lead to a weakened affective response. PMID:19562631

  5. Damage to temporo-parietal cortex decreases incidental activation of thematic relations during spoken word comprehension

    PubMed Central

    Mirman, Daniel; Graziano, Kristen M.

    2012-01-01

    Both taxonomic and thematic semantic relations have been studied extensively in behavioral studies and there is an emerging consensus that the anterior temporal lobe plays a particularly important role in the representation and processing of taxonomic relations, but the neural basis of thematic semantics is less clear. We used eye tracking to examine incidental activation of taxonomic and thematic relations during spoken word comprehension in participants with aphasia. Three groups of participants were tested: neurologically intact control participants (N=14), individuals with aphasia resulting from lesions in left hemisphere BA 39 and surrounding temporo-parietal cortex regions (N=7), and individuals with the same degree of aphasia severity and semantic impairment and anterior left hemisphere lesions (primarily inferior frontal gyrus and anterior temporal lobe) that spared BA 39 (N=6). The posterior lesion group showed reduced and delayed activation of thematic relations, but not taxonomic relations. In contrast, the anterior lesion group exhibited longer-lasting activation of taxonomic relations and did not differ from control participants in terms of activation of thematic relations. These results suggest that taxonomic and thematic semantic knowledge are functionally and neuroanatomically distinct, with the temporo-parietal cortex playing a particularly important role in thematic semantics. PMID:22571932

  6. Energy Activities for the Classroom: Volume II.

    ERIC Educational Resources Information Center

    Coon, Herbert L.; Bowman, Mary Lynne

    This resource book contains descriptions of over 100 classroom activities designed to illustrate concepts relating to energy, its production, characteristics, use, and conservations. Each activity integrates the energy lesson into a concept that relates to one or more subject areas common to public school curricula. Many of the activities included…

  7. Amygdala-ventral striatum circuit activation decreases long-term fear

    PubMed Central

    Correia, Susana S; McGrath, Anna G; Lee, Allison; Graybiel, Ann M; Goosens, Ki A

    2016-01-01

    In humans, activation of the ventral striatum, a region associated with reward processing, is associated with the extinction of fear, a goal in the treatment of fear-related disorders. This evidence suggests that extinction of aversive memories engages reward-related circuits, but a causal relationship between activity in a reward circuit and fear extinction has not been demonstrated. Here, we identify a basolateral amygdala (BLA)-ventral striatum (NAc) pathway that is activated by extinction training. Enhanced recruitment of this circuit during extinction learning, either by pairing reward with fear extinction training or by optogenetic stimulation of this circuit during fear extinction, reduces the return of fear that normally follows extinction training. Our findings thus identify a specific BLA-NAc reward circuit that can regulate the persistence of fear extinction and point toward a potential therapeutic target for disorders in which the return of fear following extinction therapy is an obstacle to treatment. DOI: http://dx.doi.org/10.7554/eLife.12669.001 PMID:27671733

  8. Amygdala-ventral striatum circuit activation decreases long-term fear

    PubMed Central

    Correia, Susana S; McGrath, Anna G; Lee, Allison; Graybiel, Ann M; Goosens, Ki A

    2016-01-01

    In humans, activation of the ventral striatum, a region associated with reward processing, is associated with the extinction of fear, a goal in the treatment of fear-related disorders. This evidence suggests that extinction of aversive memories engages reward-related circuits, but a causal relationship between activity in a reward circuit and fear extinction has not been demonstrated. Here, we identify a basolateral amygdala (BLA)-ventral striatum (NAc) pathway that is activated by extinction training. Enhanced recruitment of this circuit during extinction learning, either by pairing reward with fear extinction training or by optogenetic stimulation of this circuit during fear extinction, reduces the return of fear that normally follows extinction training. Our findings thus identify a specific BLA-NAc reward circuit that can regulate the persistence of fear extinction and point toward a potential therapeutic target for disorders in which the return of fear following extinction therapy is an obstacle to treatment. DOI: http://dx.doi.org/10.7554/eLife.12669.001

  9. Enhanced risk of thromboembolic disease in hypertension from platelet hyperfunction and decreased fibrinolytic activity: has antihypertensive therapy any influence?

    PubMed

    Winther, K; Gleerup, G; Hedner, T

    1992-01-01

    Enhanced platelet function and a decrease in fibrinolytic activity have been reported in patients with mild hypertension after treatment with various nonselective beta-blockers. Until now, such changes have not been reported during treatment with beta 1-selective drugs or with agents that have intrinsic sympathomimetic activity. The impact of angiotensin-converting enzyme inhibitors and diuretics on platelet function and fibrinolytic activity has not been fully elucidated. Calcium antagonists of various types, however, are known to decrease platelet release in vivo whereas their effects on platelet aggregation and fibrinolytic activity are less clear. The new dihydropyridine calcium antagonist isradipine, when tested in a group of patients with mild hypertension, resulted in a decrease in platelet aggregation, a shortened euglobulin clot-lysis time, and a dramatic increase in t-PA (tissue-plasminogen activator) activity after 14 days of treatment. These changes remained stable throughout the 1-year study period. The fact that antihypertensive therapy does not always result in the hoped-for prolongation of life, despite satisfactory blood pressure reduction, may be in part due to an unfavorable impact on various components of the blood-clotting system.

  10. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

    PubMed Central

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  11. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    PubMed

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  12. Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

    NASA Astrophysics Data System (ADS)

    Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

    2015-02-01

    The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

  13. Heavy metal pollution decreases microbial abundance, diversity and activity within particle-size fractions of a paddy soil.

    PubMed

    Chen, Junhui; He, Feng; Zhang, Xuhui; Sun, Xuan; Zheng, Jufeng; Zheng, Jinwei

    2014-01-01

    Chemical and microbial characterisations of particle-size fractions (PSFs) from a rice paddy soil subjected to long-term heavy metal pollution (P) and nonpolluted (NP) soil were performed to investigate whether the distribution of heavy metals (Cd, Cu, Pb and Zn) regulates microbial community activity, abundance and diversity at the microenvironment scale. The soils were physically fractionated into coarse sand, fine sand, silt and clay fractions. Long-term heavy metal pollution notably decreased soil basal respiration (a measurement of the total activity of the soil microbial community) and microbial biomass carbon (MBC) across the fractions by 3-45% and 21-53%, respectively. The coarse sand fraction was more affected by pollution than the clay fraction and displayed a significantly lower MBC content and respiration and dehydrogenase activity compared with the nonpolluted soils. The abundances and diversities of bacteria were less affected within the PSFs under pollution. However, significant decreases in the abundances and diversities of fungi were noted, which may have strongly contributed to the decrease in MBC. Sequencing of denaturing gradient gel electrophoresis bands revealed that the groups Acidobacteria, Ascomycota and Chytridiomycota were clearly inhibited under pollution. Our findings suggest that long-term heavy metal pollution decreased the microbial biomass, activity and diversity in PSFs, particularly in the large-size fractions.

  14. Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity

    PubMed Central

    Park, Joo-Man; Kim, Tae-Hyun; Jo, Seong-Ho; Kim, Mi-Young; Ahn, Yong-Ho

    2015-01-01

    Glucokinase (GK), mainly expressed in the liver and pancreatic β-cells, is critical for maintaining glucose homeostasis. GK expression and kinase activity, respectively, are both modulated at the transcriptional and post-translational levels. Post-translationally, GK is regulated by binding the glucokinase regulatory protein (GKRP), resulting in GK retention in the nucleus and its inability to participate in cytosolic glycolysis. Although hepatic GKRP is known to be regulated by allosteric mechanisms, the precise details of modulation of GKRP activity, by post-translational modification, are not well known. Here, we demonstrate that GKRP is acetylated at Lys5 by the acetyltransferase p300. Acetylated GKRP is resistant to degradation by the ubiquitin-dependent proteasome pathway, suggesting that acetylation increases GKRP stability and binding to GK, further inhibiting GK nuclear export. Deacetylation of GKRP is effected by the NAD+-dependent, class III histone deacetylase SIRT2, which is inhibited by nicotinamide. Moreover, the livers of db/db obese, diabetic mice also show elevated GKRP acetylation, suggesting a broader, critical role in regulating blood glucose. Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies. PMID:26620281

  15. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation.

    PubMed

    Demidowich, Andrew P; Davis, Angela I; Dedhia, Nicket; Yanovski, Jack A

    2016-07-01

    Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. PMID:27241260

  16. Protein-energy malnutrition decreases immune response to Leishmania chagasi vaccine in BALB/c mice.

    PubMed

    Malafaia, G; Serafim, T D; Silva, M E; Pedrosa, M L; Rezende, S A

    2009-01-01

    Protein-energy malnutrition and visceral leishmaniasis are important problems of public health affecting millions of people worldwide. Vaccine efficacy depends on the ability of individuals to mount an appropriate immune response and may be inadequate in malnourished persons. In this study, we used a mouse model to verify the effect of combined protein, iron and zinc deficiency in the response to Leishmania chagasi antigen vaccine. BALB/c mice were fed with a low-protein (3% casein), iron- and zinc-deficient diet or control diet (14% casein and sufficient in zinc and iron). After malnutrition establishment, mice were vaccinated subcutaneously with L. chagasi Ag plus saponin. After vaccination, mice were nutritionally repleted and then all mice were challenged with L. chagasi promastigotes. Four weeks later, liver and spleen parasite load was evaluated. Our data show that vaccine caused a significant reduction in parasite load in spleen and liver from mice fed with control diet. However, splenic parasitism was increased in mice fed with deficient diet and this diet caused a reduction in splenocyte IFN-gamma production in response to the vaccine in repleted mice. These data suggest that malnutrition may alter immune response to L. chagasi vaccine in BALB/c model of infection, even after nutritional repletion.

  17. Age related decrease of NOR activity in bone marrow metaphase chromosomes from healthy individuals.

    PubMed Central

    Pedrazzini, E; Mamaev, N; Slavutsky, I

    1998-01-01

    AIMS: To present data obtained from human bone marrow preparations from healthy individual showing that the proportion of metaphases with silver stained nucleolar organiser region (AgNOR) chromosomes is associated with the age of the donor. METHODS: Bone marrow preparations from eight Russian and 10 Argentinian healthy individuals donating bone marrow for heterologous transplantation were studied by silver staining. The Russian bone marrow preparations were used directly, while the bone marrow specimens from Argentinian donors were incubated for 24 hours at 37 degrees C in F-10 medium with 15% fetal bovine serum. The slides were silver stained by the one step method of Howell and Black with slight modifications. Thirty metaphases with clearly defined D and G group chromosomes were scored for the numbers of AgNORs. All metaphases that were adjacent to silver stained interphase nuclei were analysed to assess the percentage of AgNOR positive mitoses. The Kruskal Wallis test and Kendall's rank correlation coefficient (rK) were used to assess the relation between age and the percentage of AgNOR positive cells. RESULTS: The mean numbers (SE) of AgNORs per metaphase were 5.06 (0.17) and 5.56 (0.23) for the Russian and Argentinian groups, respectively, with no significant differences between the two groups. The common percentage of AgNOR positive cells decreased significantly as a function of age, with an rK = -0.57 (p < 0.0012). CONCLUSIONS: The percentages of AgNOR negative metaphases in bone marrow from healthy individuals is strongly associated with age and this may be related to age related telomere loss. PMID:9624419

  18. Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium

    PubMed Central

    Gorth, Deborah J; Puckett, Sabrina; Ercan, Batur; Webster, Thomas J; Rahaman, Mohamed; Bal, B Sonny

    2012-01-01

    A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants – titanium (Ti), polyether-ether-ketone (PEEK), and silicon nitride (Si3N4) – were tested to understand their respective susceptibility to bacterial infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface chemistry, wettability, and nanostructured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization, and growth were investigated. Ti and PEEK were received with as-machined surfaces; both materials are hydrophobic, with net negative surface charges. Two surface finishes of Si3N4 were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of Si3N4 is hydrophilic, with a net positive charge. A decreased biofilm formation was found, as well as fewer live bacteria on both the as-fired and polished Si3N4. These differences may reflect differential surface chemistry and surface nanostructure properties between the biomaterials tested. Because protein adsorption on material surfaces affects bacterial adhesion, the adsorption of fibronectin, vitronectin, and laminin on Ti, PEEK, and Si3N4 were also examined. Significantly greater amounts of these proteins adhered to Si3N4 than to Ti or PEEK. The findings of this study suggest that surface properties of biomaterials lead to differential adsorption of physiologic proteins, and that this phenomenon could explain the observed in-vitro differences in bacterial affinity for the respective biomaterials. Intrinsic biomaterial properties as they relate to resistance to bacterial colonization may reflect a novel strategy toward designing future orthopedic implants. PMID:22973102

  19. Decreased bacteria activity on Si₃N₄ surfaces compared with PEEK or titanium.

    PubMed

    Gorth, Deborah J; Puckett, Sabrina; Ercan, Batur; Webster, Thomas J; Rahaman, Mohamed; Bal, B Sonny

    2012-01-01

    A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants--titanium (Ti), polyether-ether-ketone (PEEK), and silicon nitride (Si₃N₄)--were tested to understand their respective susceptibility to bacterial infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface chemistry, wettability, and nanostructured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization, and growth were investigated. Ti and PEEK were received with as-machined surfaces; both materials are hydrophobic, with net negative surface charges. Two surface finishes of Si₃N₄ were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of Si₃N₄ is hydrophilic, with a net positive charge. A decreased biofilm formation was found, as well as fewer live bacteria on both the as-fired and polished Si₃N₄. These differences may reflect differential surface chemistry and surface nanostructure properties between the biomaterials tested. Because protein adsorption on material surfaces affects bacterial adhesion, the adsorption of fibronectin, vitronectin, and laminin on Ti, PEEK, and Si₃N₄ were also examined. Significantly greater amounts of these proteins adhered to Si₃N₄ than to Ti or PEEK. The findings of this study suggest that surface properties of biomaterials lead to differential adsorption of physiologic proteins, and that this phenomenon could explain the observed in-vitro differences in bacterial affinity for the respective biomaterials. Intrinsic biomaterial properties as they relate to resistance to bacterial colonization may reflect a novel strategy toward designing future orthopedic implants.

  20. Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation

    PubMed Central

    Luo, Lin-Na; Xie, De Qiong; Zhang, Xiao Gang; Jiang, Rong

    2016-01-01

    Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying renal I/R injury involve inflammation, oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits potential anti-inflammatory activity. The aim of the present study was to investigate the effect of osthole in renal I/R injury and its underlying mechanism. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. A total of 70 rats were randomly assigned to seven groups (n=10 per group): Sham; IRI; and osthole (0, 5, 10, 20 and 40 mg/kg) groups. Rats were administered intraperitoneally with osthole 45 min prior to renal ischemia. Serum and renal tissue were harvested 24 h after reperfusion. Renal function and histological changes were assessed. In addition, the mRNA and protein expression of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and interleukin-6 (IL-6) in renal tissue and serum were evaluated using quantitative polymerase chain reaction and ELISA assays, respectively. The protein expression levels of p65, p-p65, janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3) and p-STAT3 were measured using western blot analysis. The results indicate that osthole pretreatment was able to significantly attenuate the renal dysfunction in a dose-dependent manner, histological changes and the expression of TNF-α, IL-8, IL-6, p-JAK2, p-STAT3 and p-p65 induced by renal I/R injury. However, neither osthole or I/R injury affected the expression p65, JAK2 and STAT3. Osthole pretreatment is able to reduce renal I/R injury by abrogating inflammation and the mechanism is partially involved in suppressing JAK2/STAT3 activation. Thus, osthole may be a novel practical strategy for the mitigation of renal I/R injury. PMID:27698686

  1. Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation

    PubMed Central

    Luo, Lin-Na; Xie, De Qiong; Zhang, Xiao Gang; Jiang, Rong

    2016-01-01

    Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying renal I/R injury involve inflammation, oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits potential anti-inflammatory activity. The aim of the present study was to investigate the effect of osthole in renal I/R injury and its underlying mechanism. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. A total of 70 rats were randomly assigned to seven groups (n=10 per group): Sham; IRI; and osthole (0, 5, 10, 20 and 40 mg/kg) groups. Rats were administered intraperitoneally with osthole 45 min prior to renal ischemia. Serum and renal tissue were harvested 24 h after reperfusion. Renal function and histological changes were assessed. In addition, the mRNA and protein expression of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and interleukin-6 (IL-6) in renal tissue and serum were evaluated using quantitative polymerase chain reaction and ELISA assays, respectively. The protein expression levels of p65, p-p65, janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3) and p-STAT3 were measured using western blot analysis. The results indicate that osthole pretreatment was able to significantly attenuate the renal dysfunction in a dose-dependent manner, histological changes and the expression of TNF-α, IL-8, IL-6, p-JAK2, p-STAT3 and p-p65 induced by renal I/R injury. However, neither osthole or I/R injury affected the expression p65, JAK2 and STAT3. Osthole pretreatment is able to reduce renal I/R injury by abrogating inflammation and the mechanism is partially involved in suppressing JAK2/STAT3 activation. Thus, osthole may be a novel practical strategy for the mitigation of renal I/R injury.

  2. Is the decrease of the total electron energy density a covalence indicator in hydrogen and halogen bonds?

    PubMed

    Angelina, Emilio L; Duarte, Darío J R; Peruchena, Nélida M

    2013-05-01

    In this work, halogen bonding (XB) and hydrogen bonding (HB) complexes were studied with the aim of analyzing the variation of the total electronic energy density H(r b ) with the interaction strengthening. The calculations were performed at the MP2/6-311++G(2d,2p) level of approximation. To explain the nature of such interactions, the atoms in molecules theory (AIM) in conjunction with reduced variational space self-consistent field (RVS) energy decomposition analysis were carried out. Based on the local virial theorem, an equation to decompose the total electronic energy density H(r b ) in two energy densities, (-G(r b )) and 1/4∇(2)ρ(r b ), was derived. These energy densities were linked with the RVS interaction energy components. Through the connection between both decomposition schemes, it was possible to conclude that the decrease in H(r b ) with the interaction strengthening observed in the HB as well as the XB complexes, is mainly due to the increase in the attractive electrostatic part of the interaction energy and in lesser extent to the increase in its covalent character, as is commonly considered. PMID:23187685

  3. Is the decrease of the total electron energy density a covalence indicator in hydrogen and halogen bonds?

    PubMed

    Angelina, Emilio L; Duarte, Darío J R; Peruchena, Nélida M

    2013-05-01

    In this work, halogen bonding (XB) and hydrogen bonding (HB) complexes were studied with the aim of analyzing the variation of the total electronic energy density H(r b ) with the interaction strengthening. The calculations were performed at the MP2/6-311++G(2d,2p) level of approximation. To explain the nature of such interactions, the atoms in molecules theory (AIM) in conjunction with reduced variational space self-consistent field (RVS) energy decomposition analysis were carried out. Based on the local virial theorem, an equation to decompose the total electronic energy density H(r b ) in two energy densities, (-G(r b )) and 1/4∇(2)ρ(r b ), was derived. These energy densities were linked with the RVS interaction energy components. Through the connection between both decomposition schemes, it was possible to conclude that the decrease in H(r b ) with the interaction strengthening observed in the HB as well as the XB complexes, is mainly due to the increase in the attractive electrostatic part of the interaction energy and in lesser extent to the increase in its covalent character, as is commonly considered.

  4. High Fetal Estrogen Concentrations: Correlation with Increased Adult Sexual Activity and Decreased Aggression in Male Mice

    NASA Astrophysics Data System (ADS)

    Vom Saal, Frederick S.; Grant, William M.; McMullen, Carol W.; Laves, Kurt S.

    1983-06-01

    In the house mouse (Mus musculus), fetuses may develop in utero next to siblings of the same or opposite sex. The amniotic fluid of the female fetuses contains higher concentrations of estradiol than that of male fetuses. Male fetuses that developed in utero between female fetuses had higher concentrations of estradiol in their amniotic fluid than males that were located between other male fetusesw during intrauterine development. They were also more sexually active as adults, less aggressive, and had smaller seminal vesicles than males that had developed between other male fetuses in utero. These findings raise the possibility that during fetal life circulating estrogens may interact with circulating androgens both in regulating the development of sex differences between males and females and in producing variation in phenotype among males and among females.

  5. Decreasing relapse in colorectal cancer patients treated with cetuximab by using the activating KRAS detection chip.

    PubMed

    Huang, Ming-Yii; Liu, Hsueh-Chiao; Yen, Li-Chen; Chang, Jia-Yuan; Huang, Jian-Jhang; Wang, Jaw-Yuan; Lin, Shiu-Ru

    2014-10-01

    The KRAS oncogene was among the first genetic alterations in colorectal cancer (CRC) to be discovered. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-epidermal growth factor receptor therapeutic drugs. Because the KRAS mutations are similar in the primary CRC and/or the CRC metastasis, KRAS mutation testing can be performed on both specimen types. The purpose of this study was to investigate the clinical advantage of using a KRAS pathway-associated molecule analysis chip to analyze CRC patients treated with cetuximab. Our laboratory developed a KRAS pathway-associated molecule analysis chip and a weighted enzymatic chip array (WEnCA) technique, activating KRAS detection chip, which can detect KRAS mutation status by screening circulating cancer cells in the bloodstream. We prospectively enrolled 210 stage II-III CRC patients who received adjuvant oxaliplatin plus infusional 5-fluorouracil/leucovorin (FOLFOX)-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens with disease control status in these patients. Among the 168 CRC patients with negative chip results, 119 were treated with FOLFOX-4 plus cetuximab chemotherapy, and their relapse rate was 35.3 % (42/119). In contrast, the relapse rate was 71.4 % among the patients with negative chip results who received FOLFOX-4 treatment alone (35/49). Negative chip results were significantly correlated with better treatment outcomes in the FOLFOX-4 plus cetuximab group (P < 0.001). We suggest that the activating KRAS detection chip is a potential tool for predicting clinical outcomes in CRC patients following FOLFOX-4 treatment with or without cetuximab therapy.

  6. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

    PubMed Central

    Hua-Huy, Thông; Duong-Quy, Sy; Pham, Hoa; Pansiot, Julien; Mercier, Jean-Christophe; Baud, Olivier

    2016-01-01

    Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  7. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    PubMed Central

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  8. Permafrost thaw and intense thermokarst activity decreases abundance of stream benthic macroinvertebrates.

    PubMed

    Chin, Krista S; Lento, Jennifer; Culp, Joseph M; Lacelle, Denis; Kokelj, Steven V

    2016-08-01

    Intensification of permafrost thaw has increased the frequency and magnitude of large permafrost slope disturbances (mega slumps) in glaciated terrain of northwestern Canada. Individual thermokarst disturbances up to 40 ha in area have made large volumes of previously frozen sediments available for leaching and transport to adjacent streams, significantly increasing sediment and solute loads in these systems. To test the effects of this climate-sensitive disturbance regime on the ecology of Arctic streams, we explored the relationship between physical and chemical variables and benthic macroinvertebrate communities in disturbed and undisturbed stream reaches in the Peel Plateau, Northwest Territories, Canada. Highly disturbed and undisturbed stream reaches differed with respect to taxonomic composition and invertebrate abundance. Minimally disturbed reaches were not differentiated by these variables but rather were distributed along a disturbance gradient between highly disturbed and undisturbed sites. In particular, there was evidence of a strong negative relationship between macroinvertebrate abundance and total suspended solids, and a positive relationship between abundance and the distance from the disturbance. Increases in both sediments and nutrients appear to be the proximate cause of community differences in highly disturbed streams. Declines in macroinvertebrate abundance in response to slump activity have implications for the food webs of these systems, potentially leading to negative impacts on higher trophic levels, such as fish. Furthermore, the disturbance impacts on stream health can be expected to intensify as climate change increases the frequency and magnitude of thermokarst. PMID:26766394

  9. Permafrost thaw and intense thermokarst activity decreases abundance of stream benthic macroinvertebrates.

    PubMed

    Chin, Krista S; Lento, Jennifer; Culp, Joseph M; Lacelle, Denis; Kokelj, Steven V

    2016-08-01

    Intensification of permafrost thaw has increased the frequency and magnitude of large permafrost slope disturbances (mega slumps) in glaciated terrain of northwestern Canada. Individual thermokarst disturbances up to 40 ha in area have made large volumes of previously frozen sediments available for leaching and transport to adjacent streams, significantly increasing sediment and solute loads in these systems. To test the effects of this climate-sensitive disturbance regime on the ecology of Arctic streams, we explored the relationship between physical and chemical variables and benthic macroinvertebrate communities in disturbed and undisturbed stream reaches in the Peel Plateau, Northwest Territories, Canada. Highly disturbed and undisturbed stream reaches differed with respect to taxonomic composition and invertebrate abundance. Minimally disturbed reaches were not differentiated by these variables but rather were distributed along a disturbance gradient between highly disturbed and undisturbed sites. In particular, there was evidence of a strong negative relationship between macroinvertebrate abundance and total suspended solids, and a positive relationship between abundance and the distance from the disturbance. Increases in both sediments and nutrients appear to be the proximate cause of community differences in highly disturbed streams. Declines in macroinvertebrate abundance in response to slump activity have implications for the food webs of these systems, potentially leading to negative impacts on higher trophic levels, such as fish. Furthermore, the disturbance impacts on stream health can be expected to intensify as climate change increases the frequency and magnitude of thermokarst.

  10. HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

    SciTech Connect

    Yadav, Anjana; Pati, Shibani; Nyugen, Anhthu; Barabitskaja, Oxana; Mondal, Prosanta; Anderson, Michael; Gallo, Robert C.; Huso, David L.; Reid, William . E-mail: reid@umbi.umd.edu

    2006-09-30

    Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the {alpha}/{beta} T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells.

  11. [On the mechanism of noopept action: decrease in activity of stress-induced kinases and increase in expression of neutrophines].

    PubMed

    Ostrovskaia, R U; Vakhitova, Iu V; Salimgareeva, M Kh; Iamidanov, R S; Sadovnikov, S V; Kapitsa, I G; Seredenin, S B

    2010-12-01

    The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111)--a drug combining the nootrope and neuroprotector properties--on the activity of mitogen-activated protein kinases (MAPKs) and the level of NGF and BDNF gene and protein expression in the frontal cortex, hippocampus, and hypothalamus has been studied in rats. Under conditions of chronic administration (28 days, 0.5 mg/day, i.p.), noopept decreased the activity of stress-induced kinases (SAPK/JNK 46/54 and pERK1/2) in rat hippocampus and increases the level of mRNA of the BDNF gene in both hypothalamus and hippocampus. The content of BDNF protein in the hypothalamus was also somewhat increased. In the context of notions about the activation of stress-induced kinases, as an important factor of amyloidogenesis and tau-protein deposition in brain tissue, and the role of deficiency of the neurotrophic factors in the development of neurodegenerative processes, the observed decrease in the activity of stress-activated MAPKs and increased expression of BDNF as a result of noopept administration suggest thatthis drug hasaspecific activity withrespect to some pathogenetic mechanisms involved in the Alzheimer disease. PMID:21395007

  12. Energy balance, physical activity, and cancer risk.

    PubMed

    Fair, Alecia Malin; Montgomery, Kara

    2009-01-01

    This chapter posits that cancer is a complex and multifactorial process as demonstrated by the expression and production of key endocrine and steroid hormones that intermesh with lifestyle factors (physical activity, body size, and diet) in combination to heighten cancer risk. Excess weight has been associated with increased mortality from all cancers combined and for cancers of several specific sites. The prevalence of obesity has reached epidemic levels in many parts of the world; more than 1 billion adults are overweight with a body mass index (BMI) exceeding 25. Overweight and obesity are clinically defined indicators of a disease process characterized by the accumulation of body fat due to an excess of energy intake (nutritional intake) relative to energy expenditure (physical activity). When energy intake exceeds energy expenditure over a prolonged period of time, the result is a positive energy balance (PEB), which leads to the development of obesity. This physical state is ideal for intervention and can be modulated by changes in energy intake, expenditure, or both. Nutritional intake is a modifiable factor in the energy balance-cancer linkage primarily tested by caloric restriction studies in animals and the effect of energy availability. Restriction of calories by 10 to 40% has been shown to decrease cell proliferation, increasing apoptosis through anti-angiogenic processes. The potent anticancer effect of caloric restriction is clear, but caloric restriction alone is not generally considered to be a feasible strategy for cancer prevention in humans. Identification and development of preventive strategies that "mimic" the anticancer effects of low energy intake are desirable. The independent effect of energy intake on cancer risk has been difficult to estimate because body size and physical activity are strong determinants of total energy expenditure. The mechanisms that account for the inhibitory effects of physical activity on the carcinogenic process

  13. Solar Energy Education. Renewable energy activities for biology

    SciTech Connect

    Not Available

    1982-01-01

    An instructional aid for teachers is presented that will allow biology students the opportunity to learn about renewable energy sources. Some of the school activities include using leaves as collectors of solar energy, solar energy stored in wood, and a fuel value test for green and dry woods. A study of organic wastes as a source of fuel is included. (BCS)

  14. Solar energy education. Renewable energy activities for general science

    SciTech Connect

    Not Available

    1985-01-01

    Renewable energy topics are integrated with the study of general science. The literature is provided in the form of a teaching manual and includes such topics as passive solar homes, siting a home for solar energy, and wind power for the home. Other energy topics are explored through library research activities. (BCS)

  15. Characteristic recovery times of Forbush-type decreases in the cosmic radiation. I - Observations at earth at different energies

    NASA Technical Reports Server (NTRS)

    Lockwood, J. A.; Webber, W. R.; Jokipii, J. R.

    1986-01-01

    Data on 30 asymmetric Forbush decreases recorded by the IMP spacecraft at 1 AU and the Mt. Washington neutron monitor over the period 1972-84 are examined to characterize the recovery characteristics of cosmic rays after the events. The spacecraft data are concentrated at energies of 1.7 GV, while the terrestrial instruments recorded events at 5 GV. Attention is paid to the relative amplitudes of the recorded transient decreases, the characteristic recovery times, and the energy dependence of the amplitudes and recovery time. The recovery times were found to be equal at both energy levels, supporting a concept of energy independence for the recoveries. Also, no correlations were found between the recovery times and the occurrences of a solar magnetic field reversal or with phase in the solar modulation cycle. A time-dependent, two-dimensional model is defined, which expresses the cosmic ray particle distributions as a function of the decay of the disturbance, with a small dependence on the transport parameters of the cosmic rays.

  16. Corticosterone Blocks Ovarian Cyclicity and the LH Surge via Decreased Kisspeptin Neuron Activation in Female Mice.

    PubMed

    Luo, Elena; Stephens, Shannon B Z; Chaing, Sharon; Munaganuru, Nagambika; Kauffman, Alexander S; Breen, Kellie M

    2016-03-01

    Stress elicits activation of the hypothalamic-pituitary-adrenal axis, which leads to enhanced circulating glucocorticoids, as well as impaired gonadotropin secretion and ovarian cyclicity. Here, we tested the hypothesis that elevated, stress-levels of glucocorticoids disrupt ovarian cyclicity by interfering with the preovulatory sequence of endocrine events necessary for the LH surge. Ovarian cyclicity was monitored in female mice implanted with a cholesterol or corticosterone (Cort) pellet. Cort, but not cholesterol, arrested cyclicity in diestrus. Subsequent studies focused on the mechanism whereby Cort stalled the preovulatory sequence by assessing responsiveness to the positive feedback estradiol signal. Ovariectomized mice were treated with an LH surge-inducing estradiol implant, as well as Cort or cholesterol, and assessed several days later for LH levels on the evening of the anticipated surge. All cholesterol females showed a clear LH surge. At the time of the anticipated surge, LH levels were undetectable in Cort-treated females. In situ hybridization analyses the anteroventral periventricular nucleus revealed that Cort robustly suppressed the percentage of Kiss1 cells coexpressing cfos, as well as reduced the number of Kiss1 cells and amount of Kiss1 mRNA per cell, compared with expression in control brains. In addition, Cort blunted pituitary expression of the genes encoding the GnRH receptor and LHβ, indicating inhibition of gonadotropes during the blockage of the LH surge. Collectively, our findings support the hypothesis that physiological stress-levels of Cort disrupts ovarian cyclicity, in part, through disruption of positive feedback mechanisms at both the hypothalamic and pituitary levels which are necessary for generation of the preovulatory LH surge.

  17. Subanesthetic doses of ketamine transiently decrease serotonin transporter activity: a PET study in conscious monkeys.

    PubMed

    Yamamoto, Shigeyuki; Ohba, Hiroyuki; Nishiyama, Shingo; Harada, Norihiro; Kakiuchi, Takeharu; Tsukada, Hideo; Domino, Edward F

    2013-12-01

    Subanesthetic doses of ketamine, an N-methyl-D-aspartic acid (NMDA) antagonist, have a rapid antidepressant effect which lasts for up to 2 weeks. However, the neurobiological mechanism regarding this effect remains unclear. In the present study, the effects of subanesthetic doses of ketamine on serotonergic systems in conscious monkey brain were investigated. Five young monkeys underwent four positron emission tomography measurements with [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([(11)C]DASB) for the serotonin transporter (SERT), during and after intravenous infusion of vehicle or ketamine hydrochloride in a dose of 0.5 or 1.5 mg/kg for 40 min, and 24 h post infusion. Global reduction of [(11)C]DASB binding to SERT was observed during ketamine infusion in a dose-dependent manner, but not 24 h later. The effect of ketamine on the serotonin 1A receptor (5-HT1A-R) and dopamine transporter (DAT) was also investigated in the same subjects studied with [(11)C]DASB. No significant changes were observed in either 5-HT1A-R or DAT binding after ketamine infusion. Microdialysis analysis indicated that ketamine infusion transiently increased serotonin levels in the extracellular fluid of the prefrontal cortex. The present study demonstrates that subanesthetic ketamine selectively enhanced serotonergic transmission by inhibition of SERT activity. This action coexists with the rapid antidepressant effect of subanesthetic doses of ketamine. Further studies are needed to investigate whether the transient combination of SERT and NMDA reception inhibition enhances each other's antidepressant actions. PMID:23880871

  18. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.

    PubMed

    Briones, T L; Darwish, H

    2014-03-14

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase 2A (PP2A) activity, and modulating the redox state. Male F344 rats aged 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (n=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in the water maze started on day 14 after the initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: (1) tau phosphorylation significantly increased during aging; (2) markers of brain energy metabolism and redox state are significantly decreased in aging; and (3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggest that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.

  19. Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts.

    PubMed

    Bowman, Amy; Birch-Machin, Mark A

    2016-05-01

    The mitochondrial theory of aging remains one of the most widely accepted aging theories and implicates mitochondrial electron transport chain dysfunction with subsequent increasing free radical generation. Recently, complex II of the electron transport chain appears to be more important than previously thought in this process, suggested predominantly by nonhuman studies. We investigated the relationship between complex II and aging using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015) but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the succinate dehydrogenase complex subunit A and subunit B catalytic subunits of complex II, respectively. In addition, there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. PMID:26829036

  20. Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D2 receptors

    PubMed Central

    Watt, Michael J.; Roberts, Christina L.; Scholl, Jamie L.; Meyer, Danielle L.; Miiller, Leah C.; Barr, Jeffrey L.; Novick, Andrew M.; Renner, Kenneth J.; Forster, Gina L.

    2014-01-01

    Rationale Adverse social experience in adolescence causes reduced medial prefrontal cortex (mPFC) dopamine (DA) and associated behavioral deficits in early adulthood. Objective To determine whether mPFC DA hypofunction following social stress is specific to adolescent experience, and if this results from stress-induced DA D2 receptor activation. Materials and Methods Male rats exposed to repeated social defeat during adolescence or adulthood had mPFC DA activity sampled 17 days later. Separate experiments used freely-moving microdialysis to measure mPFC DA release in response to adolescent defeat exposure. At P40, 49 and 56 mPFC DA turnover was assessed to identify when DA activity decreased in relation to the adolescent defeat experience. Finally, non-defeated adolescent rats received repeated intra-mPFC infusions of the D2 receptor agonist quinpirole, while another adolescent group received intra-mPFC infusions of the D2 antagonist amisulpride before defeat exposure. Results Long-term decreases or increases in mPFC DA turnover were observed following adolescent or adult defeat, respectively. Adolescent defeat exposure elicits sustained increases in mPFC DA release, and DA turnover remains elevated beyond the stress experience before declining to levels below normal at P56. Activation of mPFC D2 receptors in non-defeated adolescents decreases DA activity in a similar manner to that caused by adolescent defeat, while defeat-induced reductions in mPFC DA activity are prevented by D2 receptor blockade. Conclusions Both the developing and mature PFC DA systems are vulnerable to social stress, but only adolescent defeat causes DA hypofunction. This appears to result in part from stress-induced activation of mPFC D2 autoreceptors. PMID:24271009

  1. Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells

    PubMed Central

    Reifenberger, Matthew S.; Yu, Ling; Bao, Hui-Fang; Duke, Billie Jeanne; Liu, Bing-Chen; Ma, He-Ping; Eaton, Douglas C.; Alli, Abdel A.

    2014-01-01

    Numerous reports have linked cytoskeleton-associated proteins with the regulation of epithelial Na+ channel (ENaC) activity. The purpose of the present study was to determine the effect of actin cytoskeleton disruption by cytochalasin E on ENaC activity in Xenopus 2F3 cells. Here, we show that cytochalasin E treatment for 60 min can disrupt the integrity of the actin cytoskeleton in cultured Xenopus 2F3 cells. We show using single channel patch-clamp experiments and measurements of short-circuit current that ENaC activity, but not its density, is altered by cytochalasin E-induced disruption of the cytoskeleton. In nontreated cells, 8 of 33 patches (24%) had no measurable ENaC activity, whereas in cytochalasin E-treated cells, 17 of 32 patches (53%) had no activity. Analysis of those patches that did contain ENaC activity showed channel open probability significantly decreased from 0.081 ± 0.01 in nontreated cells to 0.043 ± 0.01 in cells treated with cytochalasin E. Transepithelial current from mpkCCD cells treated with cytochalasin E, cytochalasin D, or latrunculin B for 60 min was decreased compared with vehicle-treated cells. The subcellular expression of fodrin changed significantly, and several protein elements of the cytoskeleton decreased at least twofold after 60 min of cytochalasin E treatment. Cytochalasin E treatment disrupted the association between ENaC and myristoylated alanine-rich C-kinase substrate. The results presented here suggest disruption of the actin cytoskeleton by different compounds can attenuate ENaC activity through a mechanism involving changes in the subcellular expression of fodrin, several elements of the cytoskeleton, and destabilization of the ENaC-myristoylated alanine-rich C-kinase substrate complex. PMID:24829507

  2. Antioxidative Activity after Rosuvastatin Treatment in Patients with Stable Ischemic Heart Disease and Decreased High Density Lipoprotein Cholesterol

    PubMed Central

    Park, Do-Sim; Park, Hyun Young; Rhee, Sang Jae; Kim, Nam-Ho; Oh, Seok Kyu; Jeong, Jin-Won

    2016-01-01

    Background and Objectives The clinical significance of statin-induced high-density lipoprotein cholesterol (HDL-C) changes is not well known. We investigated whether rosuvastatin-induced HDL-C changes can influence the anti-oxidative action of high-density lipoprotein particle. Subjects and Methods A total of 240 patients with stable ischemic heart disease were studied. Anti-oxidative property was assessed by paraoxonase 1 (PON1) activity. We compared the lipid profile and PON1 activity at baseline and at 8 weeks after rosuvastatin 10 mg treatment. Results Rosuvastatin treatment increased the mean HDL-C concentration by 1.9±9.2 mg/dL (6.4±21.4%). HDL-C increased in 138 patients (57.5%), but decreased in 102 patients (42.5%) after statin treatment. PON1 activity increased to 19.1% in all patients. In both, the patients with increased HDL-C and with decreased HDL-C, PON1 activity significantly increased after rosuvastatin treatment (+19.3% in increased HDL-C responder; p=0.018, +18.8% in decreased HDL-C responder; p=0.045 by paired t-test). Baseline PON1 activity modestly correlated with HDL-C levels (r=0.248, p=0.009); however, the PON1 activity evaluated during the course of the treatment did not correlate with HDL-C levels (r=0.153, p=0.075). Conclusion Rosuvastatin treatment improved the anti-oxidative properties as assessed by PON1 activity, regardless of on-treatment HDL-C levels, in patients with stable ischemic heart disease. PMID:27275167

  3. Solar Energy Project, Activities: General Solar Topics.

    ERIC Educational Resources Information Center

    Tullock, Bruce, Ed.; And Others

    This guide contains lesson plans and outlines of activities which introduce students to concepts and issues relating to solar energy. Lessons frequently presented in the context of solar energy as it relates to contemporary energy problems. Each unit presents an introduction; objectives; necessary skills and knowledge; materials; method;…

  4. Overexpression of Csk-binding protein decreases growth, invasion, and migration of esophageal carcinoma cells by controlling Src activation

    PubMed Central

    Zhou, Dong; Dong, Peng; Li, Yu-Min; Guo, Fa-Cai; Zhang, An-Ping; Song, Run-Ze; Zhang, Ya-Min; Li, Zhi-Yong; Yuan, Dong; Yang, Chuan

    2015-01-01

    AIM: To investigate the mechanisms by which Csk-binding protein (CBP) inhibits tumor progression in esophageal carcinoma. METHODS: A CBP overexpressing esophageal carcinoma cell line (TE-1) was established. The growth, invasion, and migration of CBP-TE-1 cells, as well as the expression of Src were then determined and compared with those in normal TE-1 cells. RESULTS: The expression of Src was decreased by the overexpression of CBP in TE-1 cells. The growth, invasion, and migration of TE-1 cells were decreased by the overexpression of CBP. CONCLUSION: This study indicates that CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src. CBP may be a potential tumor suppressor and targeting the CBP gene may be an alternative strategy for the development of therapies for esophageal carcinoma. PMID:25684946

  5. Activation of ERK1/2 pathway mediates oxidant-induced decreases in mitochondrial function in renal cells.

    PubMed

    Nowak, Grazyna; Clifton, Ginger L; Godwin, Malinda L; Bakajsova, Diana

    2006-10-01

    Previously, we showed that oxidant exposure in renal proximal tubular cells (RPTC) induces mitochondrial dysfunction mediated by PKC-epsilon. This study examined the role of ERK1/2 in mitochondrial dysfunction induced by oxidant injury and whether PKC-epsilon mediates its effects on mitochondrial function through the Raf-MEK1/2-ERK1/2 pathway. Sublethal injury produced by tert-butylhydroperoxide (TBHP) resulted in three- to fivefold increase in phosphorylation of ERK1/2 and p38 but not JNK. This was followed by decreases in basal and uncoupled respirations (41%), state 3 respiration and ATP production coupled to complex I (46%), and complex I activity (42%). Oxidant exposure decreased aconitase activity 30% but not pyruvate, alpha-ketoglutarate, and malate dehydrogenase activities. Inhibition of ERK1/2 restored basal and state 3 respirations, DeltaPsi(m), ATP production, and complex I activity but not aconitase activity. In contrast, activation of ERK1/2 by expression of constitutively active MEK1 suppressed basal, uncoupled, and state 3 respirations in noninjured RPTC to the levels observed in TBHP-injured RPTC. MEK1/2 inhibition did not change Akt or p38 phosphorylation, demonstrating that the protective effect of MEK1/2 inhibitor was not due to activation of Akt or inhibition of p38 pathway. Inhibition of PKC-epsilon did not block TBHP-induced ERK1/2 phosphorylation in whole RPTC or in mitochondria. We conclude that 1) oxidant-induced activation of ERK1/2 but not p38 or JNK reduces mitochondrial respiration and ATP production by decreasing complex I activity and substrate oxidation through complex I, 2) citric acid cycle dehydrogenases are not under control of the ERK1/2 pathway in oxidant-injured RPTC, 3) the protective effects of ERK1/2 inhibition are not due to activation of Akt, and 4) ERK1/2 and PKC-epsilon mediate oxidant-induced mitochondrial dysfunction through independent pathways.

  6. Hybrid energy harvesting using active thermal backplane

    NASA Astrophysics Data System (ADS)

    Kim, Hyun-Wook; Lee, Dong-Gun

    2016-04-01

    In this study, we demonstrate the concept of a new hybrid energy harvesting system by combing solar cells with magneto-thermoelectric generator (MTG, i.e., thermal energy harvesting). The silicon solar cell can easily reach high temperature under normal operating conditions. Thus the heated solar cell becomes rapidly less efficient as the temperature of solar cell rises. To increase the efficiency of the solar cell, air or water-based cooling system is used. To surpass conventional cooling devices requiring additional power as well as large working space for air/water collectors, we develop a new technology of pairing an active thermal backplane (ATB) to solar cell. The ATB design is based on MTG technology utilizing the physics of the 2nd order phase transition of active ferromagnetic materials. The MTG is cost-effective conversion of thermal energy to electrical energy and is fundamentally different from Seebeck TEG devices. The ATB (MTG) is in addition to being an energy conversion system, a very good conveyor of heat through both conduction and convection. Therefore, the ATB can provide dual-mode for the proposed hybrid energy harvesting. One is active convective and conductive cooling for heated solar cell. Another is active thermal energy harvesting from heat of solar cell. These novel hybrid energy harvesting device have potentially simultaneous energy conversion capability of solar and thermal energy into electricity. The results presented can be used for better understanding of hybrid energy harvesting system that can be integrated into commercial applications.

  7. Sonication inhibited browning but decreased polyphenols contents and antioxidant activity of fresh apple (malus pumila mill, cv. Red Fuji) juice.

    PubMed

    Sun, Yujing; Zhong, Liezhou; Cao, Lianfei; Lin, Wenwen; Ye, Xingqian

    2015-12-01

    Enzyme browning is the main challenge in the preparation of fresh apple juice. The influence of sonication on browning, as well as polyphenols and antioxidant activity of fresh apple juice was investigated. It was found that ultrasound can inhibit the browning of fresh apple (Malus pumila Mill, cv. Red Fuji) juice, but decreased the contents of total phenolic content (TPC), total flavonoid content (TFC) and chlorogenic acid and reduced the antioxidant activity. On the whole, ultrasound technology cannot be used to the antibrowning of fresh apple (Malus pumila Mill, cv. Red Fuji) juice.

  8. Decreased succinate dehydrogenase activity of gamma and alpha motoneurons in mouse spinal cords following 13 weeks of exposure to microgravity.

    PubMed

    Ishihara, Akihiko; Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Ohira, Yoshinobu

    2013-10-01

    Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (<300 μm(2)) gamma and medium-sized (300-700 μm(2)) alpha motoneurons, which have higher succinate dehydrogenase activity than large-sized (>700 μm(2)) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity. PMID:23943522

  9. Chronic inhibition of 11 β -hydroxysteroid dehydrogenase type 1 activity decreases hypertension, insulin resistance, and hypertriglyceridemia in metabolic syndrome.

    PubMed

    Schnackenberg, Christine G; Costell, Melissa H; Krosky, Daniel J; Cui, Jianqi; Wu, Charlene W; Hong, Victor S; Harpel, Mark R; Willette, Robert N; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11 β -hydroxysteroid dehydrogenase type 1 (11 β -HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11 β -HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11 β -HSD1. Compound 11 significantly decreased 11 β -HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11 β -HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  10. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    PubMed Central

    Schnackenberg, Christine G.; Costell, Melissa H.; Krosky, Daniel J.; Cui, Jianqi; Wu, Charlene W.; Hong, Victor S.; Harpel, Mark R.; Willette, Robert N.; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome. PMID:23586038

  11. Decreased succinate dehydrogenase activity of gamma and alpha motoneurons in mouse spinal cords following 13 weeks of exposure to microgravity.

    PubMed

    Ishihara, Akihiko; Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Ohira, Yoshinobu

    2013-10-01

    Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (<300 μm(2)) gamma and medium-sized (300-700 μm(2)) alpha motoneurons, which have higher succinate dehydrogenase activity than large-sized (>700 μm(2)) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity.

  12. Decrease in red blood cell deformability is associated with a reduction in RBC-NOS activation during storage.

    PubMed

    Grau, Marijke; Friederichs, Petra; Krehan, Sebastian; Koliamitra, Christina; Suhr, Frank; Bloch, Wilhelm

    2015-07-16

    During storage, red blood cells (RBC) become more susceptible to hemolysis and it has also been shown that RBC deformability, which is influenced by RBC nitric oxide synthase (RBC-NOS) activity, decreases during blood storage while a correlation between these two parameters under storage conditions has not been investigated so far. Therefore, blood from 15 male volunteers was anticoagulated, leuko-reduced and stored as either concentrated RBC or RBC diluted in saline-adenine-glucose-mannitol (SAGM) for eight weeks at 4°C and results were compared to data obtained from freshly drawn blood. During storage, decrease of RBC deformability was related to increased mean cellular volume and increased cell lysis but also to a decrease in RBC-NOS activation. The changes were more pronounced in concentrated RBC than in RBC diluted in SAGM suggesting that the storage method affects the quality of blood. These data shed new light on mechanisms underlying the phenomenon of storage lesion and reveal that RBC-NOS activation and possibly nitric oxide production in RBC are key elements that are influenced by storage and in turn alter deformability. Further studies should therefore also focus on improving these parameters during storage to improve the quality of stored blood with respect to blood transfusion.

  13. High-fat diet decreases activity of the oxidative phosphorylation complexes and causes nonalcoholic steatohepatitis in mice

    PubMed Central

    García-Ruiz, Inmaculada; Solís-Muñoz, Pablo; Fernández-Moreira, Daniel; Grau, Montserrat; Colina, Francisco; Muñoz-Yagüe, Teresa; Solís-Herruzo, José A.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most frequent histological finding in individuals with abnormal liver-function tests in the Western countries. In previous studies, we have shown that oxidative phosphorylation (OXPHOS) is decreased in individuals with NAFLD, but the cause of this mitochondrial dysfunction remains uncertain. The aims of this study were to determine whether feeding mice a high-fat diet (HFD) induces any change in the activity of OXPHOS, and to investigate the mechanisms involved in the pathogenesis of this defect. To that end, 30 mice were distributed between five groups: control mice fed a standard diet, and mice on a HFD and treated with saline solution, melatonin (an antioxidant), MnTBAP (a superoxide dismutase analog) or uric acid (a scavenger of peroxynitrite) for 28 weeks intraperitoneously. In the liver of these mice, we studied histology, activity and assembly of OXPHOS complexes, levels of subunits of these complexes, gene expression of these subunits, oxidative and nitrosative stress, and oxidative DNA damage. In HFD-fed mice, we found nonalcoholic steatohepatitis, increased gene expression of TNFα, IFNγ, MCP-1, caspase-3, TGFβ1 and collagen α1(I), and increased levels of 3-tyrosine nitrated proteins. The activity and assembly of all OXPHOS complexes was decreased to about 50–60%. The amount of all studied OXPHOS subunits was markedly decreased, particularly the mitochondrial-DNA-encoded subunits. Gene expression of mitochondrial-DNA-encoded subunits was decreased to about 60% of control. There was oxidative damage to mitochondrial DNA but not to genomic DNA. Treatment of HFD-fed mice with melatonin, MnTBAP or uric acid prevented all changes observed in untreated HFD-fed mice. We conclude that a HFD decreased OXPHOS enzymatic activity owing to a decreased amount of fully assembled complexes caused by a reduced synthesis of their subunits. Antioxidants and antiperoxynitrites prevented all of these changes, suggesting

  14. High-fat diet decreases activity of the oxidative phosphorylation complexes and causes nonalcoholic steatohepatitis in mice.

    PubMed

    García-Ruiz, Inmaculada; Solís-Muñoz, Pablo; Fernández-Moreira, Daniel; Grau, Montserrat; Colina, Francisco; Muñoz-Yagüe, Teresa; Solís-Herruzo, José A

    2014-11-01

    Nonalcoholic fatty liver disease (NAFLD) is the most frequent histological finding in individuals with abnormal liver-function tests in the Western countries. In previous studies, we have shown that oxidative phosphorylation (OXPHOS) is decreased in individuals with NAFLD, but the cause of this mitochondrial dysfunction remains uncertain. The aims of this study were to determine whether feeding mice a high-fat diet (HFD) induces any change in the activity of OXPHOS, and to investigate the mechanisms involved in the pathogenesis of this defect. To that end, 30 mice were distributed between five groups: control mice fed a standard diet, and mice on a HFD and treated with saline solution, melatonin (an antioxidant), MnTBAP (a superoxide dismutase analog) or uric acid (a scavenger of peroxynitrite) for 28 weeks intraperitoneously. In the liver of these mice, we studied histology, activity and assembly of OXPHOS complexes, levels of subunits of these complexes, gene expression of these subunits, oxidative and nitrosative stress, and oxidative DNA damage. In HFD-fed mice, we found nonalcoholic steatohepatitis, increased gene expression of TNFα, IFNγ, MCP-1, caspase-3, TGFβ1 and collagen α1(I), and increased levels of 3-tyrosine nitrated proteins. The activity and assembly of all OXPHOS complexes was decreased to about 50-60%. The amount of all studied OXPHOS subunits was markedly decreased, particularly the mitochondrial-DNA-encoded subunits. Gene expression of mitochondrial-DNA-encoded subunits was decreased to about 60% of control. There was oxidative damage to mitochondrial DNA but not to genomic DNA. Treatment of HFD-fed mice with melatonin, MnTBAP or uric acid prevented all changes observed in untreated HFD-fed mice. We conclude that a HFD decreased OXPHOS enzymatic activity owing to a decreased amount of fully assembled complexes caused by a reduced synthesis of their subunits. Antioxidants and antiperoxynitrites prevented all of these changes, suggesting that

  15. Lorcaserin, A 5-HT2C Receptor Agonist, Reduces Body Weight by Decreasing Energy Intake without Influencing Energy Expenditure

    PubMed Central

    Martin, Corby K.; Redman, Leanne M.; Zhang, Jinkun; Sanchez, Matilde; Anderson, Christen M.; Smith, Steven R.

    2011-01-01

    Context: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)2C receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). Objective: This study tested the effect of lorcaserin on EI and EE. Design, Participants, and Intervention: In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27–45 kg/m2) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1–7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. Outcomes: At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. Results: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced with lorcaserin but not placebo (mean ± sem for lorcaserin, −286 ± 86 kcal; placebo, −147 ± 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, −3.8 ± 0.4 kg; placebo, −2.2 ± 0.5 kg; P < 0.01), EI (lorcaserin, −470 ± 87 kcal; placebo, −205 ± 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. Conclusions: Lorcaserin reduces body weight through reduced EI, not altered EE or RQ. PMID:21190985

  16. Augmentation of platelet and endothelial cell eNOS activity decreases sepsis-related neutrophil-endothelial cell interactions.

    PubMed

    Khan, Raymond; Kirschenbaum, Linda A; LaRow, Catherine; Berna, Gioiamaria; Griffin, Kelly; Astiz, Mark E

    2010-03-01

    NO is an important mediator of microvascular patency and blood flow. The purpose of this study was to examine the role of enhanced eNOS activity in attenuating sepsis-induced neutrophil-endothelial cell interactions. Microslides coated with human umbilical vein endothelial cells were stimulated with plasma from patients with septic shock. Neutrophil and platelets from control subjects were also stimulated with plasma from patients in septic shock and perfused over stimulated endothelial cells. l-Arginine (LA) with and without NG-monomethyl l-arginine (LNMMA), a nonselective NOS inhibitor, and N-(3-(aminomethyl) benzyl acetamide) ethanimidamide dihydrochloride (1400W), a highly selective iNOS inhibitor, were added to the septic plasma. The number of neutrophils adherent to endothelial cells, neutrophil rolling velocity, and the number of neutrophil aggregates were determined. Cell activation and the formation of platelet-neutrophil aggregates were assessed by flow cytometry. Separate experiments were done with isolated platelets using platelet aggregometry. l-Arginine significantly decreased sepsis-related neutrophil adhesion and aggregation and increased rolling velocity. The addition of LNMMA to LA and cell suspensions reversed the effects of LA on these parameters, whereas the addition of 1400W had no effect on LA-related changes. Platelet-neutrophil aggregation, platelet aggregation, platelet activation, and neutrophil activation induced by septic plasma were also significantly decreased by LA. Again, the addition of LNMMA reversed the effects of LA on these parameters, whereas 1400W had no effect on LA-related changes. These data suggest that enhancement of platelet and endothelial cell eNOS activity decreases sepsis-induced neutrophil-endothelial cell interactions and may play a role in maintaining microvascular patency in septic shock.

  17. Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

    PubMed

    Jarjisian, Stephan G; Butler, Matthew P; Paul, Matthew J; Place, Ned J; Prendergast, Brian J; Kriegsfeld, Lance J; Zucker, Irving

    2015-02-01

    The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs.

  18. Blocking CXCL9 Decreases HIV-1 Replication and Enhances the Activity of Prophylactic Antiretrovirals in Human Cervical Tissues

    PubMed Central

    Macura, Sherrill L.; Lathrop, Melissa J.; Gui, Jiang; Doncel, Gustavo F.; Rollenhagen, Christiane

    2016-01-01

    Objectives: The interferon-gamma–induced chemokine CXCL9 is expressed in a wide range of inflammatory conditions including those affecting the female genital tract. CXCL9 promotes immune cell recruitment, activation, and proliferation. The role of CXCL9 in modulating HIV-1 infection of cervicovaginal tissues, a main portal of viral entry, however, has not been established. We report a link between CXCL9 and HIV-1 replication in human cervical tissues and propose CXCL9 as a potential target to enhance the anti–HIV-1 activity of prophylactic antiretrovirals. Design: Using ex vivo infection of human cervical tissues as a model of mucosal HIV-1 acquisition, we described the effect of CXCL9 neutralization on HIV-1 gene expression and mucosal CD4+ T-cell activation. The anti-HIV-1 activity of tenofovir, the leading mucosal pre-exposure prophylactic microbicide, alone or in combination with CXCL9 neutralization was also studied. Methods: HIV-1 replication was evaluated by p24 ELISA. HIV-1 DNA and RNA, and CD4, CCR5, and CD38 transcription were evaluated by quantitative real-time polymerase chain reaction. Frequency of activated cervical CD4+ T cells was quantified using fluorescence-activated cell sorting. Results: Antibody blocking of CXCL9 reduced HIV-1 replication by decreasing mucosal CD4+ T-cell activation. CXCL9 neutralization in combination with suboptimal concentrations of tenofovir, possibly present in the cervicovaginal tissues of women using the drug inconsistently, demonstrated an earlier and greater decrease in HIV-1 replication compared with tissues treated with tenofovir alone. Conclusions: CXCL9 neutralization reduces HIV-1 replication and may be an effective target to enhance the efficacy of prophylactic antiretrovirals. PMID:26545124

  19. Increased oxidative stress and decreased activities of Ca2+/Mg2+-ATPase and Na+/K+-ATPase in the red blood cells of the hibernating black bear

    USGS Publications Warehouse

    Chauhan, V.P.S.; Tsiouris, J.A.; Chauhan, A.; Sheikh, A.M.; Brown, W. Ted; Vaughan, M.

    2002-01-01

    During hibernation, animals undergo metabolic changes that result in reduced utilization of glucose and oxygen. Fat is known to be the preferential source of energy for hibernating animals. Malonyldialdehyde (MDA) is an end product of fatty acid oxidation, and is generally used as an index of lipid peroxidation. We report here that peroxidation of lipids is increased in the plasma and in the membranes of red blood cells in black bears during hibernation. The plasma MDA content was about four fold higher during hibernation as compared to that during the active, non-hibernating state (P < 0.0001). Similarly, MDA content of erythrocyte membranes was significantly increased during hibernation (P < 0.025). The activity of Ca2+/Mg2+-ATPase in the erythrocyte membrane was significantly decreased in the hibernating state as compared to the active state. Na+/K+-ATPase activity was also decreased, though not significant, during hibernation. These results suggest that during hibernation, the bears are under increased oxidative stress, and have reduced activities of membrane-bound enzymes such as Ca2+/Mg2+-ATPase and Na+/K+-ATPase. These changes can be considered part of the adaptive for survival process of metabolic depression. ?? 2002 Elsevier Science Inc. All rights reserved.

  20. Improving the energy efficiency of refrigeration plants by decreasing the temperature difference in air-cooled condensers

    NASA Astrophysics Data System (ADS)

    Shishov, V. V.; Talyzin, M. S.

    2015-09-01

    The electric energy consumption efficiency is estimated in comparing the real refrigeration machine cycle with the theoretical inverse Carnot cycle. The potential for saving electricity in using aircooled condensers with different values of temperature difference is shown. A procedure for calculating a refrigerating system with the evaporation temperature equal to -10°C, which corresponds at this temperature level to the thermal load of a standard supermarket, is described. The calculation was carried out taking into account the annual profile of temperatures in the indicated locality and based on the possibility of adjusting the condenser capacity for maintaining constant condensation temperature. The payback period in case of using condensers with different values of temperature difference is calculated; for example, in using condensers with a temperature difference of less than 15 K, the payback period will be less than one year. Decreasing the temperature difference results, on one hand, in a larger annual consumption of electric energy by the condenser fans, and on the other hand, it results in a lower condensation pressure, which leads to a smaller annual consumption of energy by the compressor unit. As a result, the total amount of energy consumed by the refrigeration system decreases so that despite a higher cost of condensers designed to operate at lower values of temperature difference, it becomes possible to achieve the above-mentioned payback period. Additionally, the payback period in case of using an air-cooled microchannel aluminum condenser was calculated: in case of using such a condenser with a temperature difference of 8 K instead of the condenser with the temperature difference equal to 15 K, the payback period will be less than half a year. Recommendations for designing new refrigeration systems equipped with air-cooled condensers are given.

  1. Relationship between Differential Hepatic microRNA Expression and Decreased Hepatic Cytochrome P450 3A Activity in Cirrhosis

    PubMed Central

    Goswami, Chirayu Pankaj; Nalamasu, Rohit; Li, Lang; Jones, David; Wei, Rongrong; Liu, Wanqing; Sarasani, Vishal; Janga, Sarath Chandra; Chalasani, Naga

    2013-01-01

    Background and Aim Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis. Methods Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=28) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hydroxylation in human liver microsomes. Additionally, hepatic CYP3A4 protein concentration and the expression of CYP3A4 mRNA were measured. Analyses were conducted to identify miRNAs which were differentially expressed between two groups but also were significantly associated with lower hepatic CYP3A activity. Results Hepatic CYP3A activity in cirrhotic livers was 1.7-fold lower than in the normal livers (0.28 ± 0.06 vs. 0.47 ± 0.07mL* min-1*mg protein-1 (mean ± SEM), P=0.02). Six microRNAs (miR-155, miR-454, miR-582-5p, let-7f-1*, miR-181d, and miR-500) had >1.2-fold increase in cirrhotic livers and also had significant negative correlation with hepatic CYP3A activity (range of r = -0.44 to -0.52, P <0.05). Notably, miR-155, a known regulator of liver inflammation, had the highest fold increase in cirrhotic livers (2.2-fold, P=4.16E-08) and significantly correlated with hepatic CYP3A activity (r=-0.50, P=0.017). The relative expression (2-ΔΔCt mean ± SEM) of hepatic CYP3A4 mRNA was significantly higher in cirrhotic livers (21.76 ± 2.65 vs. 5.91 ± 1.29, P=2.04E-07) but their levels did not significantly correlate with hepatic CYP3A activity (r=-0.43, P=0.08). Conclusion The strong association between certain miRNAs, notably miR-155, and lower hepatic CYP3A activity suggest that altered miRNA expression may regulate hepatic CYP3A activity. PMID:24058572

  2. Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity.

    PubMed

    Oh, J; Shin, D; Lim, K S; Lee, S; Jung, K-H; Chu, K; Hong, K S; Shin, K-H; Cho, J-Y; Yoon, S H; Ji, S C; Yu, K-S; Lee, H; Jang, I-J

    2014-06-01

    Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P-gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once-daily 100-mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined. The P-gp microRNA miR-27a increased by up to 7.67-fold (P = 0.004) and the clopidogrel area under the concentration-time curve (AUC) decreased by 14% (P > 0.05), but the AUC of H4 remained unchanged and RPI increased by up to 15% (P = 0.002) after aspirin administration. These findings indicate low-dose aspirin coadministration may decrease clopidogrel bioavailability but does not decrease its efficacy. PMID:24566733

  3. Salecan Enhances the Activities of β-1,3-Glucanase and Decreases the Biomass of Soil-Borne Fungi

    PubMed Central

    Chen, Yunmei; Xu, Haiyang; Zhou, Mengyi; Wang, Yang; Wang, Shiming; Zhang, Jianfa

    2015-01-01

    Salecan, a linear extracellular polysaccharide consisting of β-1,3-D-glucan, has potential applications in the food, pharmaceutical and cosmetic industries. The objective of this study was to evaluate the effects of salecan on soil microbial communities in a vegetable patch. Compositional shifts in the genetic structure of indigenous soil bacterial and fungal communities were monitored using culture-dependent dilution plating, culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) and quantitative PCR. After 60 days, soil microorganism counts showed no significant variation in bacterial density and a marked decrease in the numbers of fungi. The DGGE profiles revealed that salecan changed the composition of the microbial community in soil by increasing the amount of Bacillus strains and decreasing the amount of Fusarium strains. Quantitative PCR confirmed that the populations of the soil-borne fungi Fusarium oxysporum and Trichoderma spp. were decreased approximately 6- and 2-fold, respectively, in soil containing salecan. This decrease in the amount of fungi can be explained by salecan inducing an increase in the activities of β-1,3-glucanase in the soil. These results suggest the promising application of salecan for biological control of pathogens of soil-borne fungi. PMID:26247592

  4. Progressive alopecia reveals decreasing stem cell activation probability during aging of mice with epidermal deletion of DNA methyltransferase 1.

    PubMed

    Li, Ji; Jiang, Ting-Xin; Hughes, Michael W; Wu, Ping; Yu, Juehua; Widelitz, Randall B; Fan, Guoping; Chuong, Cheng-Ming

    2012-12-01

    To examine the roles of epigenetic modulation on hair follicle regeneration, we generated mice with a K14-Cre-mediated loss of DNA methyltransferase 1 (DNMT1). The mutant shows an uneven epidermal thickness and alterations in hair follicle size. When formed, hair follicle architecture and differentiation appear normal. Hair subtypes exist but hair fibers are shorter and thinner. Hair numbers appear normal at birth but gradually decrease to <50% of control in 1-year-old mice. Sections of old mutant skin show follicles in prolonged telogen with hyperplastic sebaceous glands. Anagen follicles in mutants exhibit decreased proliferation and increased apoptosis in matrix transient-amplifying cells. Although K15-positive stem cells in the mutant bulge are comparable in number to the control, their ability to proliferate and become activated to form a hair germ is reduced. As mice age, residual DNMT activity declines further, and the probability of successful anagen reentry decreases, leading to progressive alopecia. Paradoxically, there is increased proliferation in the epidermis, which also shows aberrant differentiation. These results highlight the importance of DNA methylation in maintaining stem cell homeostasis during the development and regeneration of ectodermal organs.

  5. Genistein decreases basal hepatic cytochrome P450 1A1 protein expression and activity in Swiss Webster mice.

    PubMed

    Froyen, Erik B; Steinberg, Francene M

    2016-05-01

    Soy consumption has been associated with risk reduction for chronic diseases such as cancer. One proposed mechanism for cancer prevention by soy is through decreasing cytochrome P450 1A1 (Cyp1a1) activity. However, it is not known with certainty which soy components modulate Cyp1a1, or the characteristics or mechanisms involved in the responses after short-term (<20 days) dietary treatment without concomitant carcinogen-mediated induction. Therefore, the objective was to test the hypothesis that physiologic concentrations of dietary genistein and/or daidzein will decrease basal hepatic Cyp1a1 protein expression and activity in male and female Swiss Webster mice via inhibiting the bindings of aryl hydrocarbon receptor (AhR)-AhR nuclear translocator (ARNT) and estrogen receptor-α to the Cyp1a1 promoter region xenobiotic response element. The mice were fed the AIN-93G diet supplemented with 1500 mg/kg of genistein or daidzein for up to 1 week. Genistein, but not daidzein, significantly decreased basal hepatic microsomal Cyp1a1 protein expression and activity. AhR protein expression was not altered. Molecular mechanisms were investigated in Hepa-1c1c7 cells treated with 5 μmol/L purified aglycones genistein, daidzein, or equol. Cells treated with genistein exhibited inhibitions in ARNT and estrogen receptor-α bindings to the Cyp1a1 promoter region. This study demonstrated that genistein consumption reduced constitutive hepatic Cyp1a1 protein expression and activity, thereby contributing to the understanding of how soy isoflavone aglycones modulate cytochrome P450 biotransformation enzymes.

  6. Novel sulfonanilide analogs decrease aromatase activity in breast cancer cells: synthesis, biological evaluation, and ligand-based pharmacophore identification.

    PubMed

    Su, Bin; Tian, Ran; Darby, Michael V; Brueggemeier, Robert W

    2008-03-13

    Aromatase converts androgens to estrogens and is a particularly attractive target in the treatment of estrogen receptor positive breast cancer. Previously, the COX-2 selective inhibitor nimesulide and analogs decreased aromatase expression and enzyme activity independent of COX-2 inhibition. In this manuscript, a combinatorial approach was used to generate diversely substituted novel sulfonanilides by parallel synthesis. Their pharmacological evaluation as agents for suppression of aromatase activity in SK-BR-3 breast cancer cells was extensively explored. A ligand-based pharmacophore model was elaborated for selective aromatase modulation (SAM) using the Catalyst HipHop algorithms. The best qualitative model consisted of four features: one aromatic ring, two hydrogen bond acceptors, and one hydrophobic function. Several lead compounds have also been tested in aromatase transfected MCF-7 cells, and they significantly suppressed cellular aromatase activity. The results suggest that both genomic and nongenomic mechanisms of these compounds are involved within the aromatase suppression effect. PMID:18271519

  7. Novel sulfonanilide analogs decrease aromatase activity in breast cancer cells: synthesis, biological evaluation, and ligand-based pharmacophore identification.

    PubMed

    Su, Bin; Tian, Ran; Darby, Michael V; Brueggemeier, Robert W

    2008-03-13

    Aromatase converts androgens to estrogens and is a particularly attractive target in the treatment of estrogen receptor positive breast cancer. Previously, the COX-2 selective inhibitor nimesulide and analogs decreased aromatase expression and enzyme activity independent of COX-2 inhibition. In this manuscript, a combinatorial approach was used to generate diversely substituted novel sulfonanilides by parallel synthesis. Their pharmacological evaluation as agents for suppression of aromatase activity in SK-BR-3 breast cancer cells was extensively explored. A ligand-based pharmacophore model was elaborated for selective aromatase modulation (SAM) using the Catalyst HipHop algorithms. The best qualitative model consisted of four features: one aromatic ring, two hydrogen bond acceptors, and one hydrophobic function. Several lead compounds have also been tested in aromatase transfected MCF-7 cells, and they significantly suppressed cellular aromatase activity. The results suggest that both genomic and nongenomic mechanisms of these compounds are involved within the aromatase suppression effect.

  8. Fructose decreases physical activity and increases body fat without affecting hippocampal neurogenesis and learning relative to an isocaloric glucose diet.

    PubMed

    Rendeiro, Catarina; Masnik, Ashley M; Mun, Jonathan G; Du, Kristy; Clark, Diana; Dilger, Ryan N; Dilger, Anna C; Rhodes, Justin S

    2015-04-20

    Recent evidence suggests that fructose consumption is associated with weight gain, fat deposition and impaired cognitive function. However it is unclear whether the detrimental effects are caused by fructose itself or by the concurrent increase in overall energy intake. In the present study we examine the impact of a fructose diet relative to an isocaloric glucose diet in the absence of overfeeding, using a mouse model that mimics fructose intake in the top percentile of the USA population (18% energy). Following 77 days of supplementation, changes in body weight (BW), body fat, physical activity, cognitive performance and adult hippocampal neurogenesis were assessed. Despite the fact that no differences in calorie intake were observed between groups, the fructose animals displayed significantly increased BW, liver mass and fat mass in comparison to the glucose group. This was further accompanied by a significant reduction in physical activity in the fructose animals. Conversely, no differences were detected in hippocampal neurogenesis and cognitive/motor performance as measured by object recognition, fear conditioning and rotorod tasks. The present study suggests that fructose per se, in the absence of excess energy intake, increases fat deposition and BW potentially by reducing physical activity, without impacting hippocampal neurogenesis or cognitive function.

  9. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

    PubMed Central

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-01-01

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI. PMID:26334271

  10. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats.

    PubMed

    Wang, Peng; Huang, Jian; Li, Yi; Chang, Ruiming; Wu, Haidong; Lin, Jiali; Huang, Zitong

    2015-08-31

    Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI.

  11. Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.

    PubMed

    Bonilla, E; Contreras, R; Medina-Leendertz, S; Mora, M; Villalobos, V; Bravo, Y

    2012-03-29

    The objective of this study was to investigate the effect of Minocycline in the life span, motor activity, and lipid peroxidation of Drosophila melanogaster treated with manganese. Two days after emerging from the pupa male wild-type D. melanogaster were fed for 13 days with corn media containing 15 mM manganese. Then, they were divided in six groups of 300 flies each: group (a) remained treated with manganese (Mn group); group (b) began treatment with Minocycline (0.05 mM) (Mn-Minocycline group); group (c) received no additional treatment (Mn-no treatment group); group (d) simultaneously fed with manganese and Minocycline (Mn+Minocycline group). Additionally, a control (group e) with no treatment and another group (f) fed only with Minocycline after emerging from the pupa were added. All the manganese treated flies (group a) were dead on the 25th day. The life span in group f (101.66±1.33 days, mean S.E.M.) and of group b (97.00±3.46 days) were similar, but in both cases it was significantly higher than in group e (68.33±1.76 days), group c (67.05±2.30 days) and in those of group d (37.33±0.88). Manganese (groups a and d) decreased motor activity in D. melanogaster. In the Minocycline fed flies (groups b and f) a higher motor activity was detected. In Mn-Minocycline and Mn+Minocycline treated flies a significant decrease of MDA levels was detected when compared to the Minocycline group indicating that Minocycline and Mn appear to have a synergistic effect. In conclusion, Minocycline increased the life span and motor activity and decreased MDA formation of manganese treated D. melanogaster, probably by an inhibition of the production of reactive oxygen species. Manganese also exerted an antioxidant effect as shown by the significant decrease of MDA levels when compared to control flies.

  12. Active Hexose Correlated Compound Activates Immune Function to Decrease Chlamydia trachomatis Shedding in a Murine Stress Model

    PubMed Central

    Belay, Tesfaye; Fu, Chih-lung; Woart, Anthony

    2016-01-01

    A cold-induced stress mouse model for investigating chlamydia genital infection and immune response analysis was established in our laboratory. Previous results showed that cold-induced stress results in suppression of the immune response and increased intensity of chlamydia genital infection in the mouse model. The purpose of the present study was to evaluate the potential therapeutic value of active hexose correlated compound (AHCC) against chlamydia genital infection in mice. AHCC is an extract of mushroom commonly used as a dietary supplement is known to boost the immune system. Mice were infected intravaginally with Chlamydia trachomatis after a 24-day cold-stress application. Oral administration of AHCC to stressed or non-stressed mice was carried out seven days before infection and during the course of infection along with cervicovaginal swabbing. Cytokine production by peritoneal and splenic T cells isolated from AHCC-fed stressed mice and non-stressed mice was measured ELISA. Splenic T cells from both animal groups were co-cultured with mouse monocyte J774.2 cell line or cultured by addition of supernatants of AHCC-treated J774.2 cell line for 24 hours. Infection studies showed that AHCC-feeding compared to phosphate buffered saline (PBS)-feeding to stressed mice resulted in reduced Chlamydia trachomatis shedding from the genital tract. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were significantly increased in stressed mice receiving AHCC compared to stressed mice receiving PBS. Production of interferon gamma (IFN-γ) and interleukin 2 (IL-2) in the AHCC group was significantly high compared to production in PBS-fed group. Splenic T cells from stressed and non-stressed cultured with supernatants of AHCC-treated J774.2 cell line resulted in significantly increased TNF-α or IFN-γ production. Results obtained in this study show that AHCC improves the function of immune cells as indicated by the restoration of levels of cytokines

  13. Effects of activation energy and activation volume on the temperature-dependent viscosity of water.

    PubMed

    Kwang-Hua, Chu Rainer

    2016-08-01

    Water transport in a leaf is vulnerable to viscosity-induced changes. Recent research has suggested that these changes may be partially due to variation at the molecular scale, e.g., regulations via aquaporins, that induce reductions in leaf hydraulic conductance. What are the quantitative as well as qualitative changes in temperature-dependent viscosity due to the role of aquaporins in tuning activation energy and activation volume? Using the transition-state approach as well as the boundary perturbation method, we investigate temperature-dependent viscosity tuned by activation energy and activation volume. To validate our approach, we compare our numerical results with previous temperature-dependent viscosity measurements. The rather good fit between our calculations and measurements confirms our present approach. We have obtained critical parameters for the temperature-dependent (shear) viscosity of water that might be relevant to the increasing and reducing of leaf hydraulic conductance. These parameters are sensitive to temperature, activation energy, and activation volume. Once the activation energy increases, the (shear) viscosity of water increases. Our results also show that as the activation volume increases (say, 10^{-23}m^{3}), the (shear) viscosity of water decreases significantly and the latter induces the enhancing of leaf hydraulic conductance. Within the room-temperature regime, a small increase in the activation energy will increase the water viscosity or reduce the leaf hydraulic conductance. Our approach and results can be applied to diverse plant or leaf attributes. PMID:27627349

  14. Effects of activation energy and activation volume on the temperature-dependent viscosity of water.

    PubMed

    Kwang-Hua, Chu Rainer

    2016-08-01

    Water transport in a leaf is vulnerable to viscosity-induced changes. Recent research has suggested that these changes may be partially due to variation at the molecular scale, e.g., regulations via aquaporins, that induce reductions in leaf hydraulic conductance. What are the quantitative as well as qualitative changes in temperature-dependent viscosity due to the role of aquaporins in tuning activation energy and activation volume? Using the transition-state approach as well as the boundary perturbation method, we investigate temperature-dependent viscosity tuned by activation energy and activation volume. To validate our approach, we compare our numerical results with previous temperature-dependent viscosity measurements. The rather good fit between our calculations and measurements confirms our present approach. We have obtained critical parameters for the temperature-dependent (shear) viscosity of water that might be relevant to the increasing and reducing of leaf hydraulic conductance. These parameters are sensitive to temperature, activation energy, and activation volume. Once the activation energy increases, the (shear) viscosity of water increases. Our results also show that as the activation volume increases (say, 10^{-23}m^{3}), the (shear) viscosity of water decreases significantly and the latter induces the enhancing of leaf hydraulic conductance. Within the room-temperature regime, a small increase in the activation energy will increase the water viscosity or reduce the leaf hydraulic conductance. Our approach and results can be applied to diverse plant or leaf attributes.

  15. Effects of activation energy and activation volume on the temperature-dependent viscosity of water

    NASA Astrophysics Data System (ADS)

    Kwang-Hua, Chu Rainer

    2016-08-01

    Water transport in a leaf is vulnerable to viscosity-induced changes. Recent research has suggested that these changes may be partially due to variation at the molecular scale, e.g., regulations via aquaporins, that induce reductions in leaf hydraulic conductance. What are the quantitative as well as qualitative changes in temperature-dependent viscosity due to the role of aquaporins in tuning activation energy and activation volume? Using the transition-state approach as well as the boundary perturbation method, we investigate temperature-dependent viscosity tuned by activation energy and activation volume. To validate our approach, we compare our numerical results with previous temperature-dependent viscosity measurements. The rather good fit between our calculations and measurements confirms our present approach. We have obtained critical parameters for the temperature-dependent (shear) viscosity of water that might be relevant to the increasing and reducing of leaf hydraulic conductance. These parameters are sensitive to temperature, activation energy, and activation volume. Once the activation energy increases, the (shear) viscosity of water increases. Our results also show that as the activation volume increases (say, 10-23m3 ), the (shear) viscosity of water decreases significantly and the latter induces the enhancing of leaf hydraulic conductance. Within the room-temperature regime, a small increase in the activation energy will increase the water viscosity or reduce the leaf hydraulic conductance. Our approach and results can be applied to diverse plant or leaf attributes.

  16. [A PARADIGM SHIFT IN THE PERCEPTION OF HEALTH MAINTENANCE FROM INCREASING PHYSICAL ACTIVITY TO DECREASING PHYSICAL INACTIVITY].

    PubMed

    Rotman, Dani; Constantini, Naama

    2016-06-01

    Modern man spends most of his waking hours (50-70%) in one form or another of sedentary behavior, defined as activity conducted in a sitting or reclining position involving low energy expenditure. The remaining waking hours are spent performing low intensity physical activity (25-45%) and medium-high intensity physical activity (less than 5%): Despite this distribution, medical research has focused on the impact of increasing medium-high intensity physical activity and many health organizations' recommendations are in accordance. In recent years, research conducted has begun to examine the effect inactivity has on health and has shown that excess sedentary behaviour is an independent risk factor for a wide range of medical problems such as obesity, metabolic syndrome, poor cardiovascular health profile, diabetes mellitus, and possibly cancer. Although the higher risk brought on by sedentary behaviour is partially reduced by increasing medium-high intensity physical activity, it is not completely neutralized. One way to diminish the harm caused by long hours of sitting is to take short breaks during periods of prolonged sitting in order to walk. According to these findings, it is worthwhile to recommend reducing the hours spent in sedentary behaviour, or at least to take frequent short breaks ("activity snacks") during periods of prolonged sitting to get up and walk around. PMID:27544992

  17. P2Y2 receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37

    PubMed Central

    Dominguez Rieg, J. A.; Burt, J. M.; Ruth, P.; Rieg, T.

    2015-01-01

    Aims Nucleotides are important paracrine regulators of vascular tone. We previously demonstrated that activation of P2Y2 receptors causes an acute, NO-independent decrease in blood pressure, indicating this signalling pathway requires an endothelial-derived hyperpolarization (EDH) response. To define the mechanisms by which activation of P2Y2 receptors initiates EDH and vasodilation, we studied intermediate-conductance (KCa3.1, expressed in endothelial cells) and big-conductance potassium channels (KCa1.1, expressed in smooth muscle cells) as well as components of the myoendothelial gap junction, connexins 37 and 40 (Cx37, Cx40), all hypothesized to be part of the EDH response. Methods We compared the effects of a P2Y2/4 receptor agonist in wild-type (WT) mice and in mice lacking KCa3.1, KCa1.1, Cx37 or Cx40 under anaesthesia, while monitoring intra-arterial blood pressure and heart rate. Results Acute activation of P2Y2/4 receptors (0.01–3 mg kg−1 body weight i.v.) caused a biphasic blood pressure response characterized by a dose-dependent and rapid decrease in blood pressure in WT (maximal response % of baseline at 3 mg kg−1: −38 ± 1%) followed by a consecutive increase in blood pressure (+44 ± 11%). The maximal responses in KCa3.1−/− and Cx37−/− were impaired (−13 ± 5, +17 ± 7 and −27 ± 1, +13 ± 3% respectively), whereas the maximal blood pressure decrease in response to acetylcholine at 3 µg kg−1 was not significantly different (WT: −53 ± 3%; KCa3.1−/−: −52 ± 3; Cx37−/−: −53 ± 3%). KCa1.1−/− and Cx40−/− showed an identical biphasic response to P2Y2/4 receptor activation compared to WT. Conclusions The data suggest that the P2Y2/4 receptor activation elicits blood pressure responses via distinct mechanisms involving KCa3.1 and Cx37. PMID:25545736

  18. Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase activity in peripheral lymphocytes of patients undergoing bone marrow transplantation.

    PubMed Central

    Lee, S. M.; Crowther, D.; Scarffe, J. H.; Dougal, M.; Elder, R. H.; Rafferty, J. A.; Margison, G. P.

    1992-01-01

    O6-alkylguanine-DNA-alkyltransferase (ATase) levels were measured in extracts of peripheral blood lymphocytes taken at various times during chemotherapy from 19 patients with various haematological malignancies. Seven patients with advanced Hodgkin's disease received preparative treatment consisting of cyclophosphamide (1.5 g m-2, daily) administered on days 1 to 4 and BCNU (600 mg m-2) on day 5 prior to autologous bone marrow rescue (ABMR) delivered on day 7. Treatment in the remaining 12 patients consisted of cyclophosphamide (1.8 g m-2, daily) given on days 1 and 2 followed at day 4 with total body irradiation (TBI) administered in six fractions over the subsequent 3 days to a total dose of 1200 cGy prior to bone marrow transplantation. In the Hodgkin's group, significant decreases in ATase activity were seen during the cyclophosphamide treatment, and the median ATase nadir was 32% (range 0% to 57%) of pretreatment levels following 4 days of cyclophosphamide. In one patient, no ATase activity was detectable following the 4th cyclophosphamide treatment. ATase activities decreased further after BCNU administration to a median of 19% (range 0% to 32%) of pretreatment levels. Extensive cyclophosphamide-induced reduction of lymphocyte ATase levels was also seen in the other group of 12 patients treated with cyclophosphamide/TBI: postcyclophosphamide median ATase nadir was 35% (range 12% to 78%) of the pretreatment levels. No ATase depletion was seen when cyclophosphamide (up to 10 mM) was incubated for 2 h with pure recombinant human ATase in vitro whereas ATase activity was reduced by 90% on preincubation with 100 microns acrolein or with greater than 1 mM phosphoramide mustard. This suggests that a cyclophosphamide-induced decrease in ATase levels in human peripheral lymphocytes in vivo may be due to depletion mediated by the production of intracellular acrolein. Since ATase appears to be a principal mechanism in cellular resistance to the cytotoxic effects of BCNU

  19. Acetylsalicylic acid and salicylic acid decrease tumor cell viability and glucose metabolism modulating 6-phosphofructo-1-kinase structure and activity.

    PubMed

    Spitz, Guilherme A; Furtado, Cristiane M; Sola-Penna, Mauro; Zancan, Patricia

    2009-01-01

    The common observation that cancer cells present higher glycolytic rates when compared to control cells leads to the proposal of glycolysis as a potential target for the development of anti-tumoral agents. Anti-inflammatory drugs, such as acetylsalicylic acid (ASA) and salicylic acid (SA), present anti-tumoral properties, inducing apoptosis and altering tumor glucose utilization. The present work aims at evaluating whether ASA could directly decrease cell glycolysis through inhibition of the major regulatory enzyme within this pathway, 6-phosphofructo-1-kinase (PFK). We show that ASA and SA inhibit purified PFK in a dose-dependent manner, and that this inhibition occurs due to the modulation of the enzyme quaternary structure. ASA and SA promote the dissociation of the enzyme active tetramers into quite inactive dimers, a common regulatory mechanism of this enzyme. The inhibitory effects of ASA and SA on PFK are fully reversible and can be prevented or reverted by the binding of the enzyme to the actin filaments. Both drugs are also able to decrease glucose consumption by human breast cancer cell line MCF-7, as well as its viability, which decrease parallelly to the inhibition of PFK on these cells. In the end, we demonstrate the ability of ASA and SA to directly modulate an important regulatory intracellular enzyme, and propose that this is one of their mechanisms promoting anti-tumoral effects.

  20. Decreased number and bactericidal activity against Staphylococcus aureus of the resident cells in milk of dairy cows during early lactation.

    PubMed

    Dosogne, H; Vangroenweghe, F; Barrio, B; Rainard, P; Burvenich, C

    2001-11-01

    Phagocytic and bactericidal activity of polymorphonuclear neutrophil leukocytes (PMN) isolated from blood and milk, against Staphylococcus aureus, was compared between groups of six healthy dairy cows in early, mid- and late lactation using a bacteriological assay. PMN were isolated from blood with a high degree of purity, but the cells isolated from milk contained variable amounts of macrophages (Mphi) and lymphocytes (L). The results were therefore calculated using the percentage PMN in order to evaluate phagocytosis and killing by PMN only. Blood PMN phagocytosed 82% Staph. aureus and milk PMN 43% on average and there was no significant difference between the different stages of lactation. The bactericidal activity of blood PMN against Staph. aureus was 36+/-8% in early lactation (significantly different from mid lactation, P < 0.05), 64+/-10% in mid lactation and 53+/-6% in late lactation. Milk PMN killed only 6+/-3% Staph. aureus in early lactation (significantly different from mid lactation, P < 0.01), 27+/-3% in mid lactation and 20+/-9% Staph. aureus in late lactation. The ratio of the bactericidal activity of milk to blood PMN was 0.08, 0.43 and 0.22 in early, mid- and late lactation, respectively. In addition to the decreased function. the number of cells in milk (somatic cell count, SCC) was also 60% lower in early lactation than in mid lactation cows (P < 0.01). Our results suggest an impairment of blood and milk-resident PMN bactericidal activity against Staph. aureus and a decreased number of milk-resident PMN in dairy cows at the onset of lactation.

  1. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid.

    PubMed

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel C T; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

  2. Carboxylation of multiwalled carbon nanotube enhanced its biocompatibility with L02 cells through decreased activation of mitochondrial apoptotic pathway.

    PubMed

    Liu, Zhenbao; Dong, Xia; Song, Liping; Zhang, Hailing; Liu, Lanxia; Zhu, Dunwan; Song, Cunxian; Leng, Xigang

    2014-03-01

    Modification of carbon nanotubes (CNTs) with carboxyl group is one of the widely used strategies to increase their water dispersibility. Various molecules can be further coupled to the surface of carboxylated CNTs for the desired applications. However, the effect of carboxylation of CNTs on their cytotoxicity is far from being completely understood. In this study, the impact of carboxylated multiwalled CNT (MWCNT-COOH) on human normal liver cell line L02 was studied and compared with pristine multiwalled CNT (p-MWCNT). The data accumulated in this study revealed that modification with carboxyl group reduced the toxicity of MWCNT on L02 cells, probably due to the decreased activation of mitochondria mediated apoptotic pathway. Both p-MWCNT and MWCNT-COOH, when reaching to certain concentration, induced significant decrease in the mitochondrial membrane potential, enhanced release of cytochrome c from the mitochondria to cytoplasm as well as activation of caspase-9, and -3. However, the changes induced by MWCNT-COOH were significantly milder than that by p-MWCNT. Our observation suggests that carboxylated MWCNTs might be safer for in vivo application as compared with p-MWCNT.

  3. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid.

    PubMed

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel C T; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects.

  4. Decreased exploratory activity in a mouse model of 15q duplication syndrome; implications for disturbance of serotonin signaling.

    PubMed

    Tamada, Kota; Tomonaga, Shozo; Hatanaka, Fumiyuki; Nakai, Nobuhiro; Takao, Keizo; Miyakawa, Tsuyoshi; Nakatani, Jin; Takumi, Toru

    2010-12-15

    Autism spectrum disorders (ASDs) have garnered significant attention as an important grouping of developmental brain disorders. Recent genomic studies have revealed that inherited or de novo copy number variations (CNVs) are significantly involved in the pathophysiology of ASDs. In a previous report from our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral analyses revealed paternally duplicated (patDp/+) mice displayed abnormal behaviors resembling the symptoms of ASDs. In the present study, we extended these findings by performing various behavioral tests with C57BL/6J patDp/+ mice, and comprehensively measuring brain monoamine levels with ex vivo high performance liquid chromatography. Compared with wild-type controls, patDp/+ mice exhibited decreased locomotor and exploratory activities in the open field test, Y-maze test, and fear-conditioning test. Furthermore, their decreased activity levels overcame increased appetite induced by 24 hours of food deprivation in the novelty suppressed feeding test. Serotonin levels in several brain regions of adult patDp/+ mice were lower than those of wild-type control, with no concurrent changes in brain levels of dopamine or norepinephrine. Moreover, analysis of monoamines in postnatal developmental stages demonstrated reduced brain levels of serotonin in young patDp/+ mice. These findings suggest that a disrupted brain serotonergic system, especially during postnatal development, may generate the phenotypes of patDp/+ mice.

  5. MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation.

    PubMed

    Lahiri, Amit; Hedl, Matija; Abraham, Clara

    2015-08-18

    Inflammatory bowel disease (IBD) is characterized by dysregulated host:microbial interactions and cytokine production. Host pattern recognition receptors (PRRs) are critical in regulating these interactions. Multiple genetic loci are associated with IBD, but altered functions for most, including in the rs713875 MTMR3/HORMAD2/LIF/OSM region, are unknown. We identified a previously undefined role for myotubularin-related protein 3 (MTMR3) in amplifying PRR-induced cytokine secretion in human macrophages and defined MTMR3-initiated mechanisms contributing to this amplification. MTMR3 decreased PRR-induced phosphatidylinositol 3-phosphate (PtdIns3P) and autophagy levels, thereby increasing PRR-induced caspase-1 activation, autocrine IL-1β secretion, NFκB signaling, and, ultimately, overall cytokine secretion. This MTMR3-mediated regulation required the N-terminal pleckstrin homology-GRAM domain and Cys413 within the phosphatase domain of MTMR3. In MTMR3-deficient macrophages, reducing the enhanced autophagy or restoring NFκB signaling rescued PRR-induced cytokines. Macrophages from rs713875 CC IBD risk carriers demonstrated increased MTMR3 expression and, in turn, decreased PRR-induced PtdIns3P and autophagy and increased PRR-induced caspase-1 activation, signaling, and cytokine secretion. Thus, the rs713875 IBD risk polymorphism increases MTMR3 expression, which modulates PRR-induced outcomes, ultimately leading to enhanced PRR-induced cytokines.

  6. MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation

    PubMed Central

    Lahiri, Amit; Hedl, Matija; Abraham, Clara

    2015-01-01

    Inflammatory bowel disease (IBD) is characterized by dysregulated host:microbial interactions and cytokine production. Host pattern recognition receptors (PRRs) are critical in regulating these interactions. Multiple genetic loci are associated with IBD, but altered functions for most, including in the rs713875 MTMR3/HORMAD2/LIF/OSM region, are unknown. We identified a previously undefined role for myotubularin-related protein 3 (MTMR3) in amplifying PRR-induced cytokine secretion in human macrophages and defined MTMR3-initiated mechanisms contributing to this amplification. MTMR3 decreased PRR-induced phosphatidylinositol 3-phosphate (PtdIns3P) and autophagy levels, thereby increasing PRR-induced caspase-1 activation, autocrine IL-1β secretion, NFκB signaling, and, ultimately, overall cytokine secretion. This MTMR3-mediated regulation required the N-terminal pleckstrin homology-GRAM domain and Cys413 within the phosphatase domain of MTMR3. In MTMR3-deficient macrophages, reducing the enhanced autophagy or restoring NFκB signaling rescued PRR-induced cytokines. Macrophages from rs713875 CC IBD risk carriers demonstrated increased MTMR3 expression and, in turn, decreased PRR-induced PtdIns3P and autophagy and increased PRR-induced caspase-1 activation, signaling, and cytokine secretion. Thus, the rs713875 IBD risk polymorphism increases MTMR3 expression, which modulates PRR-induced outcomes, ultimately leading to enhanced PRR-induced cytokines. PMID:26240347

  7. IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation

    PubMed Central

    Mansoori, Mohd Nizam; Shukla, Priyanka; Kakaji, Manisha; Tyagi, Abdul M; Srivastava, Kamini; Shukla, Manoj; Dixit, Manisha; Kureel, Jyoti; Gupta, Sushil; Singh, Divya

    2016-01-01

    IL-18BP is a natural antagonist of pro-inflammatory IL-18 cytokine linked to autoimmune disorders like rheumatoid arthritis. However, its role in post menopausal osteoporosis is still unknown. In this study, we investigated the role of IL-18BP on murine osteoblasts, its effect on osteoblasts-CD4+ T cells and osteoblasts-CD11b+ macrophage co-culture. mIL-18BPd enhances osteoblast differentiation and inhibits the activation of NLRP3 inflammasome and caspase-1 which process IL-18 to its active form. Using estrogen deficient mice, we also determined the effect of mIL-18BP on various immune and skeletal parameters. Ovariectomized mice treated with mIL-18BPd exhibited decrease in Th17/Treg ratio and pro-inflammatory cytokines. mIL-18BPd treatment restored trabecular microarchitecture, preserved cortical bone parameters likely attributed to an increased number of bone lining cells and reduced osteoclastogenesis. Importantly, these results were corroborated in female osteoporotic subjects where decreased serum IL-18BP levels and enhanced serum IL-18 levels were observed. Our study forms a strong basis for using humanized IL-18BP towards the treatment of postmenopausal osteoporosis. PMID:27649785

  8. IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation.

    PubMed

    Mansoori, Mohd Nizam; Shukla, Priyanka; Kakaji, Manisha; Tyagi, Abdul M; Srivastava, Kamini; Shukla, Manoj; Dixit, Manisha; Kureel, Jyoti; Gupta, Sushil; Singh, Divya

    2016-01-01

    IL-18BP is a natural antagonist of pro-inflammatory IL-18 cytokine linked to autoimmune disorders like rheumatoid arthritis. However, its role in post menopausal osteoporosis is still unknown. In this study, we investigated the role of IL-18BP on murine osteoblasts, its effect on osteoblasts-CD4+ T cells and osteoblasts-CD11b+ macrophage co-culture. mIL-18BPd enhances osteoblast differentiation and inhibits the activation of NLRP3 inflammasome and caspase-1 which process IL-18 to its active form. Using estrogen deficient mice, we also determined the effect of mIL-18BP on various immune and skeletal parameters. Ovariectomized mice treated with mIL-18BPd exhibited decrease in Th17/Treg ratio and pro-inflammatory cytokines. mIL-18BPd treatment restored trabecular microarchitecture, preserved cortical bone parameters likely attributed to an increased number of bone lining cells and reduced osteoclastogenesis. Importantly, these results were corroborated in female osteoporotic subjects where decreased serum IL-18BP levels and enhanced serum IL-18 levels were observed. Our study forms a strong basis for using humanized IL-18BP towards the treatment of postmenopausal osteoporosis. PMID:27649785

  9. Channeling Children's Energy through Vocabulary Activities

    ERIC Educational Resources Information Center

    Schindler, Andrea

    2006-01-01

    In this article, the author shares vocabulary development activities for young learners. These activities channel students' energy and make learning more effective and fun. The author stresses the importance of giving young learners a good language-learning experience, and the challenges of teaching young learners who are not literate in their L1.…

  10. Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine.

    PubMed

    Gassen, Nils C; Fries, Gabriel R; Zannas, Anthony S; Hartmann, Jakob; Zschocke, Jürgen; Hafner, Kathrin; Carrillo-Roa, Tania; Steinbacher, Jessica; Preißinger, S Nicole; Hoeijmakers, Lianne; Knop, Matthias; Weber, Frank; Kloiber, Stefan; Lucae, Susanne; Chrousos, George P; Carell, Thomas; Ising, Marcus; Binder, Elisabeth B; Schmidt, Mathias V; Rüegg, Joëlle; Rein, Theo

    2015-11-24

    Epigenetic processes, such as DNA methylation, and molecular chaperones, including FK506-binding protein 51 (FKBP51), are independently implicated in stress-related mental disorders and antidepressant drug action. FKBP51 associates with cyclin-dependent kinase 5 (CDK5), which is one of several kinases that phosphorylates and activates DNA methyltransferase 1 (DNMT1). We searched for a functional link between FKBP51 (encoded by FKBP5) and DNMT1 in cells from mice and humans, including those from depressed patients, and found that FKBP51 competed with its close homolog FKBP52 for association with CDK5. In human embryonic kidney (HEK) 293 cells, expression of FKBP51 displaced FKBP52 from CDK5, decreased the interaction of CDK5 with DNMT1, reduced the phosphorylation and enzymatic activity of DNMT1, and diminished global DNA methylation. In mouse embryonic fibroblasts and primary mouse astrocytes, FKBP51 mediated several effects of paroxetine, namely, decreased the protein-protein interactions of DNMT1 with CDK5 and FKBP52, reduced phosphorylation of DNMT1, and decreased the methylation and increased the expression of the gene encoding brain-derived neurotrophic factor (Bdnf). In human peripheral blood cells, FKBP5 expression inversely correlated with both global and BDNF methylation. Peripheral blood cells isolated from depressed patients that were then treated ex vivo with paroxetine revealed that the abundance of BDNF positively correlated and phosphorylated DNMT1 inversely correlated with that of FKBP51 in cells and with clinical treatment success in patients, supporting the relevance of this FKBP51-directed pathway that prevents epigenetic suppression of gene expression. PMID:26602018

  11. D-psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet.

    PubMed

    Ochiai, Masaru; Onishi, Kana; Yamada, Takako; Iida, Tetsuo; Matsuo, Tatsuhiro

    2014-03-01

    We investigated the anti-obesity effects of D-psicose by increasing energy expenditure in rats pair-fed the high-sucrose diet (HSD). Wistar rats were divided into two dietary groups: HSD containing 5% cellulose (C) and 5% d-psicose (P). The C dietary group was further subdivided into two groups: rats fed the C diet ad libitum (C-AD) and pair-fed the C diet along with those in the P group (C-PF). Resting energy expenditure during darkness and lipoprotein lipase activity in the soleus muscle were significantly higher in the P group than in the C-PF group. Serum levels of glucose, leptin and adiponectin; glucose-6-phosphate dehydrogenase activities in the liver and perirenal adipose tissue; and body fat accumulation were all significantly lower in the P group than in the C-PF group. The anti-obesity effects of D-psicose could be induced not only by suppressing lipogenic enzyme activity but also by increasing EE in rats.

  12. Venom of Parasitoid Pteromalus puparum Impairs Host Humoral Antimicrobial Activity by Decreasing Host Cecropin and Lysozyme Gene Expression

    PubMed Central

    Fang, Qi; Wang, Bei-Bei; Ye, Xin-Hai; Wang, Fei; Ye, Gong-Yin

    2016-01-01

    Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Here, we report that Pteromalus puparum venom impairs the antimicrobial activity of its host Pieris rapae. Inhibition zone results showed that bead injection induced the antimicrobial activity of the host hemolymph but that venom inhibited it. The cDNAs encoding cecropin and lysozyme were screened. Relative quantitative PCR results indicated that all of the microorganisms and bead injections up-regulated the transcript levels of the two genes but that venom down-regulated them. At 8 h post bead challenge, there was a peak in the transcript level of the cecropin gene, whereas the peak of lysozyme gene occurred at 24 h. The transcripts levels of the two genes were higher in the granulocytes and fat body than in other tissues. RNA interference decreased the transcript levels of the two genes and the antimicrobial activity of the pupal hemolymph. Venom injections similarly silenced the expression of the two genes during the first 8 h post-treatment in time- and dose-dependent manners, after which the silence effects abated. Additionally, recombinant cecropin and lysozyme had no significant effect on the emergence rate of pupae that were parasitized by P. puparum females. These findings suggest one mechanism of impairing host antimicrobial activity by parasitoid venom. PMID:26907346

  13. Polymorphism rs7278468 is associated with Age-related cataract through decreasing transcriptional activity of the CRYAA promoter

    PubMed Central

    Ma, Xiaoyin; Jiao, Xiaodong; Ma, Zhiwei; Hejtmancik, J. Fielding

    2016-01-01

    CRYAA plays critical functional roles in lens transparency and opacity, and polymorphisms near CRYAA have been associated with age-related cataract (ARC). This study examines polymorphisms in the CRYAA promoter region for association with ARC and elucidates the mechanisms of this association. Three SNPs nominally associated with ARC were identified in the promoter region of CRYAA: rs3761382 (P = 0.06, OR (Odds ratio) = 1.5), rs13053109 (P = 0.04, OR = 1.6), rs7278468 (P = 0.007, OR = 0.6). The C-G-T haplotype increased the risk for ARC overall (P = 0.005, OR = 1.8), and both alleles and haplotypes show a stronger association with cortical cataract (rs3761382, P = 0.002, OR = 2.1; rs13053109, P = 0.002, OR = 2.1; rs7278468, P = 0.0007, OR = 0.5; C-G-T haplotype, P = 0.0003, OR = 2.2). The C-G-T risk haplotype decreased transcriptional activity through rs7278468, which lies in a consensus binding site for the transcription repressor KLF10. KLF10 binding inhibited CRYAA transcription, and both binding and inhibition were greater with the T rs7278468 allele. Knockdown of KLF10 in HLE cells partially rescued the transcriptional activity of CRYAA with rs7278468 T allele, but did not affect activity with the G allele. Thus, our data suggest that the T allele of rs7278468 in the CRYAA promoter is associated with ARC through increasing binding of KLF-10 and thus decreasing CRYAA transcription. PMID:26984531

  14. An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men.

    PubMed

    Allirot, Xavier; Saulais, Laure; Seyssel, Kevin; Graeppi-Dulac, Julia; Roth, Hubert; Charrié, Anne; Drai, Jocelyne; Goudable, Joelle; Blond, Emilie; Disse, Emmanuel; Laville, Martine

    2013-02-17

    The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure. PMID

  15. An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men.

    PubMed

    Allirot, Xavier; Saulais, Laure; Seyssel, Kevin; Graeppi-Dulac, Julia; Roth, Hubert; Charrié, Anne; Drai, Jocelyne; Goudable, Joelle; Blond, Emilie; Disse, Emmanuel; Laville, Martine

    2013-02-17

    The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure.

  16. Neuregulin1-β decreases interleukin-1β-induced RhoA activation, myosin light chain phosphorylation, and endothelial hyperpermeability.

    PubMed

    Wu, Limin; Ramirez, Servio H; Andrews, Allison M; Leung, Wendy; Itoh, Kanako; Wu, Jiang; Arai, Ken; Lo, Eng H; Lok, Josephine

    2016-01-01

    Neuregulin-1 (NRG1) is an endogenous growth factor with multiple functions in the embryonic and postnatal brain. The NRG1 gene is large and complex, transcribing more than twenty transmembrane proteins and generating a large number of isoforms in tissue and cell type-specific patterns. Within the brain, NRG1 functions have been studied most extensively in neurons and glia, as well as in the peripheral vasculature. Recently, NRG1 signaling has been found to be important in the function of brain microvascular endothelial cells, decreasing IL-1β-induced increases in endothelial permeability. In the current experiments, we have investigated the pathways through which the NRG1-β isoform acts on IL-1β-induced endothelial permeability. Our data show that NRG1-β increases barrier function, measured by transendothelial electrical resistance, and decreases IL-1β-induced hyperpermeability, measured by dextran-40 extravasation through a monolayer of brain microvascular endothelial cells plated on transwells. An investigation of key signaling proteins suggests that the effect of NRG1-β on endothelial permeability is mediated through RhoA activation and myosin light chain phosphorylation, events which affect filamentous actin morphology. In addition, AG825, an inhibitor of the erbB2-associated tyrosine kinase, reduces the effect of NRG1-β on IL-1β-induced RhoA activation and myosin light chain phosphorylation. These data add to the evidence that NRG1-β signaling affects changes in the brain microvasculature in the setting of neuroinflammation. We propose the following events for neuregulin-1-mediated effects on Interleukin-1 β (IL-1β)-induced endothelial hyperpermeability: IL-1β leads to RhoA activation, resulting in an increase in phosphorylation of myosin light chain (MLC). Phosphorylation of MLC is known to result in actin contraction and alterations in the f-actin cytoskeletal structure. These changes are associated with increased endothelial permeability

  17. Solar Energy Education. Renewable energy activities for earth science

    SciTech Connect

    Not Available

    1980-01-01

    A teaching manual is provided to aid teachers in introducing renewable energy topics to earth science students. The main emphasis is placed on solar energy. Activities for the student include a study of the greenhouse effect, solar gain for home heating, measuring solar radiation, and the construction of a model solar still to obtain fresh water. Instructions for the construction of apparatus to demonstrate a solar still, the greenhouse effect and measurement of the altitude and azimuth of the sun are included. (BCS)

  18. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    PubMed

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity. PMID:26896238

  19. Serum free estradiol and estrogen receptor-α mediated activity are related to decreased incident hip fractures in older women.

    PubMed

    Lim, Vanessa W; Li, Jun; Gong, Yinhan; Yuan, Jian-Min; Wu, Tsung Sheng; Hammond, Geoffrey L; Jin, Aizhen; Koh, Woon-Puay; Yong, E L

    2012-06-01

    There is paucity of data from Asian women on the association between serum estrogens and osteoporotic hip fracture risk. We conducted a case-control study nested within a population-based prospective cohort, The Singapore Chinese Health Study, to evaluate serum estrogens levels, ERα-mediated estrogenic activity and hip fracture risk in postmenopausal Asian women. Among 35,298 women who were recruited between 1993 and 1998, 15,410 women donated blood for research between 1999 and 2004. From this subcohort, we identified 140 cases who subsequently suffered hip fracture after blood donation, and 278 age-matched controls. Serum levels of total estrone, estradiol and sex hormone binding globulin levels were measured in a blinded fashion among cases and controls. ERα-mediated estrogenic activity of serum samples was quantified using a sensitive ERα-driven cell bioassay. Women with hip fracture had lower serum estrogens than control women. Compared to the lowest quintile, women in the highest quintile of free estradiol exhibited a statistically significant 57% reduction in risk of hip fracture (95% confidence interval (CI), 6-80%), with a dose-dependent relationship (p for trend=0.021). High levels of ERα-mediated estrogenic activity were also associated with decreased risk of hip fracture (p for trend=0.048). Overall, women with relatively high levels of both free estradiol and ERα-mediated estrogenic activity had a 55% reduction in hip fracture risk (95% CI, 17-76%) compared to women with low levels of both. High levels of free estradiol and ERα-mediated estrogen activity in sera were associated with reduced hip fracture risk in Chinese postmenopausal women.

  20. Maternal Hypoxia Increases the Activity of MMPs and Decreases the Expression of TIMPs in the Brain of Neonatal Rats

    PubMed Central

    Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P.; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H.; Tang, Jiping

    2010-01-01

    A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. PMID:20017119

  1. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    PubMed

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

  2. Does decreased orographic enhancement explain declining annual streamflows and recent increases in wildfire fire activity in the Pacific Northwestern US?

    NASA Astrophysics Data System (ADS)

    Holden, Z. A.; Luce, C.; Morgan, P.; Crimmins, M.; Abatzoglou, J. T.

    2013-12-01

    The influences of changing snowpack on the hydrology of the western US have been well noted, with trends in snowpack declines, early streamflow timing and associated fire activity attributed primarily to warming temperatures. We present several lines of evidence suggesting that historical declines in high elevation precipitation have contributed to early snowmelt timing, reduced annual streamflow, and increased annual area burned in the Pacific Northwest. Using satellite-derived estimates of area burned and area burned severely, we show that annual flow, an integrator of basin-wide precipitation, explains three times as much of the variability in interannual wildfire activity as does the center of timing of annual flow absent the influence of flow variability. Precipitation and snowpack are fundamentally connected to the timing of snowmelt. Thus, while annual wildfire area burned is correlated with snowmelt timing, precipitation quantity and distribution provide a more direct mechanistic explanation of recent wildfire activity in this region. The magnitude of streamflow declines cannot be explained by either increased evapotranspiration or decreases in precipitation at low elevation weather stations, implicating declining orographic enhancement as a possible mechanism for the substantial declines in streamflow observed in recent decades.

  3. Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

    PubMed Central

    Mumcu, Ugur Yilmaz; Kocer, Ibrahim; Ates, Orhan; Alp, H. Hakan

    2016-01-01

    To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development. PMID:27803873

  4. Increased hepcidin in transferrin-treated thalassemic mice correlates with increased liver BMP2 expression and decreased hepatocyte ERK activation

    PubMed Central

    Chen, Huiyong; Choesang, Tenzin; Li, Huihui; Sun, Shuming; Pham, Petra; Bao, Weili; Feola, Maria; Westerman, Mark; Li, Guiyuan; Follenzi, Antonia; Blanc, Lionel; Rivella, Stefano; Fleming, Robert E.; Ginzburg, Yelena Z.

    2016-01-01

    Iron overload results in significant morbidity and mortality in β-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in β-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbbth1/th1 (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes from apo-transferrin-treated mice demonstrate decreased ERK1/2 pathway and increased serum BMP2 concentration and hepatocyte BMP2 expression. Furthermore, hepatocyte ERK1/2 phosphorylation is enhanced by neutralizing anti-BMP2/4 antibodies and suppressed in vitro in a dose-dependent manner by BMP2, resulting in converse effects on hepcidin expression, and hepatocytes treated with MEK/ERK1/2 inhibitor U0126 in combination with BMP2 exhibit an additive increase in hepcidin expression. Lastly, bone marrow erythroferrone expression is normalized in apo-transferrin treated thalassemic mice but increased in apo-transferrin injected wild-type mice. These findings suggest that increased hepcidin expression after exogenous apo-transferrin is in part independent of erythroferrone and support a model in which apo-transferrin treatment in thalassemic mice increases BMP2 expression in the liver and other organs, decreases hepatocellular ERK1/2 activation, and increases nuclear Smad to increase hepcidin expression in hepatocytes. PMID:26635037

  5. Decreases in energy and increases in phase locking of event-related oscillations to auditory stimuli occur during adolescence in human and rodent brain.

    PubMed

    Ehlers, Cindy L; Wills, Derek N; Desikan, Anita; Phillips, Evelyn; Havstad, James

    2014-01-01

    Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of changes in brain remodeling that occur during adolescence. This study sought to investigate developmental changes in EROs using a similar auditory event-related potential (ERP) paradigm in both rats and humans. Energy and phase variability of EROs collected from 38 young adult men (aged 18-25 years), 33 periadolescent boys (aged 10-14 years), 15 male periadolescent rats [at postnatal day (PD) 36] and 19 male adult rats (at PD103) were investigated. Three channels of ERP data (frontal cortex, central cortex and parietal cortex) were collected from the humans using an 'oddball plus noise' paradigm that was presented under passive (no behavioral response required) conditions in the periadolescents and under active conditions (where each subject was instructed to depress a counter each time he detected an infrequent target tone) in adults and adolescents. ERPs were recorded in rats using only the passive paradigm. In order to compare the tasks used in rats to those used in humans, we first studied whether three ERO measures [energy, phase locking index (PLI) within an electrode site and phase difference locking index (PDLI) between different electrode sites] differentiated the 'active' from 'passive' ERP tasks. Secondly, we explored our main question of whether the three ERO measures differentiated adults from periadolescents in a similar manner in both humans and rats. No significant changes were found in measures of ERO energy between the active and passive tasks in the periadolescent human participants. There was a smaller but significant increase in PLI but not PDLI as a function of active task requirements. Developmental differences were found in energy, PLI and PDLI values between the periadolescents and adults in

  6. Decreases in energy and increases in phase locking of event-related oscillations to auditory stimuli occur during adolescence in human and rodent brain.

    PubMed

    Ehlers, Cindy L; Wills, Derek N; Desikan, Anita; Phillips, Evelyn; Havstad, James

    2014-01-01

    Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of changes in brain remodeling that occur during adolescence. This study sought to investigate developmental changes in EROs using a similar auditory event-related potential (ERP) paradigm in both rats and humans. Energy and phase variability of EROs collected from 38 young adult men (aged 18-25 years), 33 periadolescent boys (aged 10-14 years), 15 male periadolescent rats [at postnatal day (PD) 36] and 19 male adult rats (at PD103) were investigated. Three channels of ERP data (frontal cortex, central cortex and parietal cortex) were collected from the humans using an 'oddball plus noise' paradigm that was presented under passive (no behavioral response required) conditions in the periadolescents and under active conditions (where each subject was instructed to depress a counter each time he detected an infrequent target tone) in adults and adolescents. ERPs were recorded in rats using only the passive paradigm. In order to compare the tasks used in rats to those used in humans, we first studied whether three ERO measures [energy, phase locking index (PLI) within an electrode site and phase difference locking index (PDLI) between different electrode sites] differentiated the 'active' from 'passive' ERP tasks. Secondly, we explored our main question of whether the three ERO measures differentiated adults from periadolescents in a similar manner in both humans and rats. No significant changes were found in measures of ERO energy between the active and passive tasks in the periadolescent human participants. There was a smaller but significant increase in PLI but not PDLI as a function of active task requirements. Developmental differences were found in energy, PLI and PDLI values between the periadolescents and adults in

  7. Behavioral activation and problem-solving therapy for depressed breast cancer patients: preliminary support for decreased suicidal ideation.

    PubMed

    Hopko, D R; Funderburk, J S; Shorey, R C; McIndoo, C C; Ryba, M M; File, A A; Benson, K; Vitulano, M

    2013-11-01

    Major depressive disorder (MDD) is the most common psychiatric disorder in breast cancer patients. The prevalence of suicidal ideation in breast cancer patients is considerable, and relative to the general population, the prevalence of completed suicide is elevated, particularly in cancer patients with MDD. A major component of suicide prevention is effective treatment of MDD. Although some research has explored the utility of psychotherapy with breast cancer patients, only three trials have explored the benefits of behavior therapy in patients with well-diagnosed MDD and there has been no systematic investigation of the potential benefits of psychotherapy toward reducing suicidal ideation in breast cancer patients. As a follow-up to a recently completed randomized trial, this study examined the efficacy of 8 weeks of behavioral activation treatment for depression (BATD) and problem-solving therapy (PST) in reducing depression and suicidal ideation, as well as increasing hopefulness in breast cancer patients with MDD (n = 80). Across both treatments, GEE analyses revealed decreased depression and suicidal ideation and increased hopefulness at posttreatment, results that were maintained at 12-month follow-up. Moreover, follow-up patient contact at approximately 2 years posttreatment yielded no indication of completed suicide. Although these data are preliminary, BATD and PST may represent practical approaches to decrease suicidal ideation in depressed breast cancer patients.

  8. Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus.

    PubMed

    Gorelik, Gabriela; Fang, Jing Yuan; Wu, Ailing; Sawalha, Amr H; Richardson, Bruce

    2007-10-15

    T cells from patients with lupus or treated with the lupus-inducing drug hydralazine have defective ERK phosphorylation. The reason for the impaired signal transduction is unknown but important to elucidate, because decreased T cell ERK pathway signaling causes a lupus-like disease in animal models by decreasing DNA methyltransferase expression, leading to DNA hypomethylation and overexpression of methylation-sensitive genes with subsequent autoreactivity and autoimmunity. We therefore analyzed the PMA stimulated ERK pathway phosphorylation cascade in CD4(+) T cells from patients with lupus and in hydralazine-treated cells. The defect in these cells localized to protein kinase C (PKC)delta. Pharmacologic inhibition of PKCdelta or transfection with a dominant negative PKCdelta mutant caused demethylation of the TNFSF7 (CD70) promoter and CD70 overexpression similar to lupus and hydralazine-treated T cells. These results suggest that defective T cell PKCdelta activation may contribute to the development of idiopathic and hydralazine-induced lupus through effects on T cell DNA methylation.

  9. Jumihaidokuto (Shi-Wei-Ba-Du-Tang), a Kampo Formula, Decreases the Disease Activity of Palmoplantar Pustulosis

    PubMed Central

    Mizawa, Megumi; Makino, Teruhiko; Inami, Chieko; Shimizu, Tadamichi

    2016-01-01

    Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by sterile intraepidermal pustules associated with erythematous scaling on the palms and soles. Jumihaidokuto is a traditional herbal medicine composed of ten medical plants and has been given to patients with suppurative skin disease in Japan. This study investigated the effect of jumihaidokuto on the disease activity in PPP patients (n = 10). PPP patients were given jumihaidokuto (EKT-6; 6.0 g per day) for 4 to 8 weeks in addition to their prescribed medications. The results showed that the palmoplantar pustular psoriasis area and severity index (PPPASI) was decreased after the administration of jumihaidokuto (p < 0.05). Therefore, Jumihaidokuto is seemingly effective against PPP. PMID:27143961

  10. Inhibition of acetylcholinesterase activity by rivastigmine decreases lipopolysaccharide-induced IL-1β expression in the hypothalamus of ewes.

    PubMed

    Herman, A P; Krawczyńska, A; Bochenek, J; Haziak, K; Antushevitch, H; Herman, A; Tomaszewska-Zaremba, D

    2013-04-01

    The present study was designed to determine the effect of subcutaneous rivastigmine treatment on IL-1β expression and IL-1 type I receptor (IL-1R1) gene expression in the hypothalamic structures (preoptic area [POA], anterior hypothalamus [AHA], and medial basal hypothalamus [MBH]) of ewes after lipopolysaccharide (LPS) treatment. Endotoxin treatment increased (P ≤ 0.01) both IL-1β and IL-1R1 gene expression in the POA, AHA, and MBH compared with the control group, whereas concomitant rivastigmine and LPS injection abolished this stimulatory effect. It was also found that LPS elevated (P ≤ 0.01) IL-1β concentration in the hypothalamus (71.0 ± 2.3 pg/mg) compared with controls (16.1 ± 3.6 pg/mg). The simultaneous injection of LPS and rivastigmine did not increase IL-1β concentration in the hypothalamus (24.6 ± 13.0 pg/mg). This central change in IL-1β synthesis seems to be an effect of acetylcholinesterase (AChE) inhibition by rivastigmine, which decreases (P ≤ 0.01) the activity of this enzyme from 78.5 ± 15.0 μmol · min(-1) · g(-1) of total protein in the control and 68.8 ± 9.8 μmol · min(-1) · g(-1) of total protein in LPS-treated animals to 45.2 ± 5.6 μmol · min(-1) · g(-1) of total protein in the rivastigmine and LPS-treated group. Our study showed that rivastigmine could effectively reverse the stimulatory effect of immune stress induced by LPS injection on IL-1β synthesis through a decrease in AChE activity in the hypothalamic area of sheep. Our results also proved that the cholinergic anti-inflammatory pathway could directly modulate the central response to endotoxin.

  11. Plasma membrane aquaporin activity can affect the rate of apoptosis but is inhibited after apoptotic volume decrease.

    PubMed

    Jablonski, Elizabeth M; Webb, Ashley N; McConnell, Nisha A; Riley, Marcus C; Hughes, Francis M

    2004-04-01

    Apoptosis is characterized by a conserved series of morphological events beginning with the apoptotic volume decrease (AVD). This study investigated a role for aquaporins (AQPs) during the AVD. Inhibition of AQPs blocked the AVD in ovarian granulosa cells undergoing growth factor withdrawal and blocked downstream apoptotic events such as cell shrinkage, changes in the mitochondrial membrane potential, DNA degradation, and caspase-3 activation. The effects of AQP inhibition on the AVD and DNA degradation were consistent in thymocytes and with two additional apoptotic signals, thapsigargin and C(6)-ceramide. Overexpression of AQP-1 in Chinese hamster ovary (CHO-AQP-1) cells enhanced their rate of apoptosis. The AVD is driven by loss of K(+) from the cell, and we hypothesize that after the AVD, AQPs become inactive, which halts further water loss and allows K(+) concentrations to decrease to levels necessary for apoptotic enzyme activation. Swelling assays on granulosa cells, thymocytes, and CHO-AQP-1 cells revealed that indeed, the shrunken (apoptotic) subpopulation has very low water permeability compared with the normal-sized (nonapoptotic) subpopulation. In thymocytes, AQP-1 is present and was shown to colocalize with the plasma membrane receptor tumor necrosis factor receptor-1 (TNF-R1) both before and after the AVD, which suggests that this protein is not proteolytically cleaved and remains on the cell membrane. Overall, these data indicate that AQP-mediated water loss is important for the AVD and downstream apoptotic events, that the water permeability of the plasma membrane can control the rate of apoptosis, and that inactivation after the AVD may help create the low K(+) concentration that is essential in apoptotic cells. Furthermore, inactivation of AQPs after the AVD does not appear to be through degradation or removal from the cell membrane.

  12. Active TGF-β signaling and decreased expression of PTEN separates angiosarcoma of bone from its soft tissue counterpart.

    PubMed

    Verbeke, Sofie L J; Bertoni, Franco; Bacchini, Patrizia; Oosting, Jan; Sciot, Raf; Krenács, Tibor; Bovée, Judith V M G

    2013-09-01

    Angiosarcomas constitute a heterogeneous group of highly malignant vascular tumors. Angiosarcoma of bone is rare and poorly characterized. For angiosarcoma of soft tissue, some pathways seem to be involved in tumor development. Our aim was to evaluate the role of these pathways in angiosarcoma of bone. We collected 37 primary angiosarcomas of bone and used 20 angiosarcomas of soft tissue for comparison. Immunohistochemistry was performed on constructed tissue microarrays to evaluate expression of CDKN2A, TP53, PTEN, BCL2, CDK4, MDM2, cyclin D1, β-catenin, transforming growth factor-β (TGF-β), CD105, phospho-Smad1, phospho-Smad2, hypoxia-inducible factor-1α, plasminogen activator inhibitor type 1 (PAI-1), VEGF, CD117 and glucose transporter--1. PIK3CA was screened for hotspot mutations in 19 angiosarcomas. In nearly 55% of the angiosarcoma of bone, the retinoblastoma (Rb) pathway was affected. Loss of CDKN2A expression was associated with a significantly worse prognosis. No overexpression of TP53 or MDM2 was found, suggesting that the TP53 pathway is not important in angiosarcoma of bone. Angiosarcoma of bone showed highly active TGF-β signaling with immunoreactivity for phospho-Smad2 and PAI-1. Although the phosphatidylinositol 3-kinase (PI3K)/Akt pathway seems to be active in both tumor groups, different mechanisms were involved: 41% of angiosarcoma of bone showed a decrease in expression of PTEN, whereas in angiosarcoma of soft tissue overexpression of KIT was found (90%). PIK3CA hotspot mutations were absent. In conclusion, the Rb pathway is involved in tumorigenesis of angiosarcoma of bone. The PI3K/Akt pathway is activated in both angiosarcoma of bone and soft tissue, however, with a different cause; PTEN expression is decreased in angiosarcoma of bone, whereas angiosarcomas of soft tissue show overexpression of KIT. Our findings support that angiosarcomas are a heterogeneous group of vascular malignancies. Both angiosarcoma of bone and soft tissue may

  13. Conservation Activities Related to Energy: Energy Activities for Urban Elementary Students, K-6.

    ERIC Educational Resources Information Center

    Schmidt, Joan S.; And Others

    Presented are simple activities, experiments, and demonstrations relating to energy conservation in the home. Activities are divided into four areas: (1) kitchen, (2) house, (3) transportation, and (4) heating and cooling. The material has been designed to require a minimum of preparation. Activity and game masters are provided. Activities may be…

  14. Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levelsa

    PubMed Central

    Dahlhoff, Christoph; Worsch, Stefanie; Sailer, Manuela; Hummel, Björn A.; Fiamoncini, Jarlei; Uebel, Kirsten; Obeid, Rima; Scherling, Christian; Geisel, Jürgen; Bader, Bernhard L.; Daniel, Hannelore

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic lipid accumulation and steatosis, and is closely linked to liver one-carbon (C1) metabolism. We assessed in C57BL6/N mice whether NAFLD induced by a high-fat (HF) diet over 8 weeks can be reversed by additional 4 weeks of a dietary methyl-donor supplementation (MDS). MDS in the obese mice failed to reverse NAFLD, but prevented the progression of hepatic steatosis associated with major changes in key hepatic C1-metabolites, e.g. S-adenosyl-methionine and S-adenosyl-homocysteine. Increased phosphorylation of AMPK-α together with enhanced β-HAD activity suggested an increased flux through fatty acid oxidation pathways. This was supported by concomitantly decreased hepatic free fatty acid and acyl-carnitines levels. Although HF diet changed the hepatic phospholipid pattern, MDS did not. Our findings suggest that dietary methyl-donors activate AMPK, a key enzyme in fatty acid β-oxidation control, that mediates increased fatty acid utilization and thereby prevents further hepatic lipid accumulation. PMID:25061561

  15. Lactobacillus rhamnosus GG decreases TNF-alpha production in lipopolysaccharide-activated murine macrophages by a contact-independent mechanism.

    PubMed

    Peña, Jeremy Andrew; Versalovic, James

    2003-04-01

    Animal studies and human clinical trials have shown that Lactobacillus can prevent or ameliorate inflammation in chronic colitis. However, molecular mechanisms for this effect have not been clearly elucidated. We hypothesize that lactobacilli are capable of downregulating pro-inflammatory cytokine responses induced by the enteric microbiota. We investigated whether lactobacilli diminish production of tumour necrosis factor alpha (TNF-alpha) by the murine macrophage line, RAW 264.7 gamma (NO-), and alter the TNF-alpha/interleukin-10 (IL-10) balance, in vitro. When media conditioned by Lactobacillus rhamnosus GG (LGG) are co-incubated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA), TNF-alpha production is significantly inhibited compared to controls, whereas IL-10 synthesis is unaffected. Interestingly, LGG-conditioned media also decreases TNF-alpha production of Helicobacter-conditioned media-activated peritoneal macrophages. Lactobacillus species may be capable of producing soluble molecules that inhibit TNF-alpha production in activated macrophages. As overproduction of pro-inflammatory cytokines, especially TNF-alpha, is implicated in pathogenesis of chronic intestinal inflammation, enteric Lactobacillus-mediated inhibition of pro-inflammatory cytokine production and alteration of cytokine profiles may highlight an important immunomodulatory role for commensal bacteria in the gastrointestinal tract.

  16. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes.

    PubMed

    Majithia, Amit R; Flannick, Jason; Shahinian, Peter; Guo, Michael; Bray, Mark-Anthony; Fontanillas, Pierre; Gabriel, Stacey B; Rosen, Evan D; Altshuler, David

    2014-09-01

    Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decreased risk of type 2 diabetes (T2D). Whether and how rare variants in PPARG and defects in adipocyte differentiation influence risk of T2D in the general population remains undetermined. By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF < 0.5%). Considered in aggregate (with or without computational prediction of functional consequence), these rare variants showed no association with T2D (OR = 1.35; P = 0.17). The function of the 49 variants was experimentally tested in a novel high-throughput human adipocyte differentiation assay, and nine were found to have reduced activity in the assay. Carrying any of these nine LOF variants was associated with a substantial increase in risk of T2D (OR = 7.22; P = 0.005). The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D.

  17. mTOR inhibition decreases SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance

    PubMed Central

    Garros-Regulez, Laura; Aldaz, Paula; Arrizabalaga, Olatz; Moncho-Amor, Veronica; Carrasco-Garcia, Estefania; Manterola, Lorea; Moreno-Cugnon, Leire; Barrena, Cristina; Villanua, Jorge; Ruiz, Irune; Pollard, Steven; Lovell-Badge, Robin; Sampron, Nicolas; Garcia, Idoia; Matheu, Ander

    2016-01-01

    ABSTRACT Background: SOX2 and SOX9 are commonly overexpressed in glioblastoma, and regulate the activity of glioma stem cells (GSCs). Their specific and overlapping roles in GSCs and glioma treatment remain unclear. Methods: SOX2 and SOX9 levels were examined in human biopsies. Gain and loss of function determined the impact of altering SOX2 and SOX9 on cell proliferation, senescence, stem cell activity, tumorigenesis and chemoresistance. Results: SOX2 and SOX9 expression correlates positively in glioma cells and glioblastoma biopsies. High levels of SOX2 bypass cellular senescence and promote resistance to temozolomide. Mechanistic investigations revealed that SOX2 acts upstream of SOX9. mTOR genetic and pharmacologic (rapamycin) inhibition decreased SOX2 and SOX9 expression, and reversed chemoresistance. Conclusions: Our findings reveal SOX2-SOX9 as an oncogenic axis that regulates stem cell properties and chemoresistance. We identify that rapamycin abrogate SOX protein expression and provide evidence that a combination of rapamycin and temozolomide inhibits tumor growth in cells with high SOX2/SOX9. PMID:26878385

  18. Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesion.

    PubMed

    Kavoussi, S K; Witz, C A; Binkley, P A; Nair, A S; Lebovic, D I

    2009-10-01

    The aim of this study was to investigate whether peroxisome proliferator-activated receptor (PPAR)-gamma activation has an effect on the attachment of endometrial cells to peritoneal mesothelial cells in a well-established in vitro model of the early endometriotic lesion. The endometrial epithelial cell line EM42 and mesothelial cell line LP9 were used for this study. EM42 cells, LP9 cells or both were treated with the PPAR-gamma agonist ciglitazone (CTZ) at varying concentrations (10, 20 and 40 microM) x 48 h with subsequent co-culture of EM42 and LP9 cells. The rate of EM42 attachment and invasion through LP9 cells was then assessed and compared with control (EM42 and LP9 cells co-cultured without prior treatment with CTZ). Next, attachment of CTZ-treated and untreated EM42 cells to hyaluronic acid (HA), a cell adhesion molecule (CAM) on peritoneal mesothelial cells, were assessed. Although there was no difference in EM42 attachment when LP9 cells alone were treated with CTZ, treatment of EM42 cells with 40 microM CTZ decreased EM42 attachment to LP9 cells by 27% (P < 0.01). Treatment of both EM42 and LP9 cells with 40 microM CTZ decreased EM42 attachment to LP9 by 37% (P < 0.01). Treatment of EM42 cells with 40 microM CTZ decreased attachment to HA by 66% (P = 0.056). CTZ did not decrease invasion of EM42 cells through the LP9 monolayer. CTZ may inhibit EM42 cell proliferation. In conclusion, CTZ significantly decreased EM42 attachment to LP9 cells and HA in an in vitro model of the early endometriotic lesion. PMID:19643817

  19. Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts.

    PubMed

    Gardner, Nicole M; Riley, Ronald T; Showker, Jency L; Voss, Kenneth A; Sachs, Andrew J; Maddox, Joyce R; Gelineau-van Waes, Janee B

    2016-05-01

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in the nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. PMID:26905748

  20. TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways

    PubMed Central

    Jung, Jong Gab; Yi, Sang-A; Choi, Sung-E; Kang, Yup; Kim, Tae Ho; Jeon, Ja Young; Bae, Myung Ae; Ahn, Jin Hee; Jeong, Hana; Hwang, Eun Sook; Lee, Kwan-Woo

    2015-01-01

    The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2′-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-phosphoeIF2α-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance. PMID:26537193

  1. Solar Energy Project, Activities: Junior High Science.

    ERIC Educational Resources Information Center

    Tullock, Bruce, Ed.; And Others

    This guide contains lesson plans and outlines of science activities which present concepts of solar energy in the context of the junior high science curriculum. Each unit presents an introduction; objectives; skills and knowledge needed; materials; methods; questions; recommendations for further work; and a teacher information sheet. The teacher…

  2. Solar Energy Project, Activities: Earth Science.

    ERIC Educational Resources Information Center

    Tullock, Bruce, Ed.; And Others

    This guide contains lesson plans and outlines of science activities which present concepts of solar energy in the context of earth science experiments. Each unit presents an introduction; objectives; skills and knowledge needed; materials; method; questions; recommendations for further study; and a teacher information sheet. The teacher…

  3. Energy Activities for Junior High Social Studies.

    ERIC Educational Resources Information Center

    Minnesota State Energy Agency, St. Paul.

    The document contains seven learning activities for junior high students on the energy situation. Objectives are to help students gain understanding and knowledge about the relationships between humans and their social and physical environments; solve problems and clarify issues; examine personal beliefs and values; and recognize the relationships…

  4. Solar Energy Project, Activities: Chemistry & Physics.

    ERIC Educational Resources Information Center

    Tullock, Bruce, Ed.; And Others

    This guide contains lesson plans and outlines of science activities which present concepts of solar energy in the context of chemistry and physics experiments. Each unit presents an introduction to the unit; objectives; required skills and knowledge; materials; method; questions; recommendations for further work; and a teacher information sheet.…

  5. A high isoflavone diet decreases 5' adenosine monophosphate-activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice.

    PubMed

    Stallings, Michael T; Cardon, Brandon R; Hardman, Jeremy M; Bliss, Tyler A; Brunson, Scott E; Hart, Chris M; Swiss, Maria D; Hepworth, Squire D; Christensen, Merrill J; Hancock, Chad R

    2014-04-01

    Selenium (Se) has been implicated as a micronutrient that decreases adenosine monophosphate-activated protein kinase (AMPK) signaling and may increase diabetes risk by reducing insulin sensitivity. Soy isoflavones (IF) are estrogen-like compounds that have been shown to attenuate insulin resistance, hyperglycemia, adiposity, and increased AMPK activation. We hypothesized that a high IF (HIF) diet would prevent the poor metabolic profile associated with high Se intake. The purpose of this study was to examine changes in basal glucose metabolism and AMPK signaling in response to an HIF diet and/or supplemental Se in a mouse model. Male FVB mice were divided into groups receiving either a control diet with minimal IF (low IF) or an HIF diet. Each dietary group was further subdivided into groups receiving either water or Se at a dose of 3 mg Se/kg body weight daily, as Se-methylselenocysteine (SMSC). After 5 months, mice receiving SMSC had elevated fasting glucose (P < .05) and a tendency for glucose intolerance (P = .08). The increase in dietary IF did not result in improved fasting blood glucose. Interestingly, after 6 months, HIF-fed mice had decreased basal AMPK activation in liver and skeletal muscle tissue (P < .05). Basal glucose metabolism was changed by SMSC supplementation as evidenced by increased fasting blood glucose and glucose intolerance. High dietary IF levels did not protect against aberrant blood glucose. In FVB mice, decreased basal AMPK activation is not the mechanism through which Se exerts its effect. These results suggest that more research must be done to elucidate the role of Se and IF in glucose metabolism.

  6. Impurity-to-band activation energy in phosphorus doped diamond

    NASA Astrophysics Data System (ADS)

    Stenger, I.; Pinault-Thaury, M.-A.; Kociniewski, T.; Lusson, A.; Chikoidze, E.; Jomard, F.; Dumont, Y.; Chevallier, J.; Barjon, J.

    2013-08-01

    The value of the impurity-to-band activation energy EA of a dopant is a basic feature of the electrical conductivity of semiconductors. Various techniques were used to determine EA in n-type diamond doped with phosphorus, giving values of EA varying from 0.43 eV to 0.63 eV, the value EA of 0.6 eV being commonly accepted for the ionization energy of phosphorus donors in diamond. Nevertheless, up to now, the dispersion of the experimental values of EA remains unexplained. In this work, we investigate the electrical properties of a set of n-type diamond homoepitaxial films with different phosphorus concentrations by Hall effect measurements in order to deduce EA and to understand the evolution of this energy with the dopant concentration. We show that, below 2 × 1019 cm-3 phosphorus, the decrease of EA is mainly controlled by the concentration of ionized defects resulting from the donor compensation. The role of ionized defects in the decrease of EA is analyzed on the basis of existing models adapted to the case of diamond. The proposed model provides a correct description of the experimental data. It can be used to quantitatively predict the activation energy of phosphorus in n-type diamond for given donor and compensating acceptor concentrations.

  7. Enhanced photosynthetic performance and growth as a consequence of decreasing mitochondrial malate dehydrogenase activity in transgenic tomato plants.

    PubMed

    Nunes-Nesi, Adriano; Carrari, Fernando; Lytovchenko, Anna; Smith, Anna M O; Loureiro, Marcelo Ehlers; Ratcliffe, R George; Sweetlove, Lee J; Fernie, Alisdair R

    2005-02-01

    Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the mitochondrial malate dehydrogenase gene in the antisense orientation and exhibiting reduced activity of this isoform of malate dehydrogenase show enhanced photosynthetic activity and aerial growth under atmospheric conditions (360 ppm CO2). In comparison to wild-type plants, carbon dioxide assimilation rates and total plant dry matter were up to 11% and 19% enhanced in the transgenics, when assessed on a whole-plant basis. Accumulation of carbohydrates and redox-related compounds such as ascorbate was also markedly elevated in the transgenics. Also increased in the transgenic plants was the capacity to use L-galactono-lactone, the terminal precursor of ascorbate biosynthesis, as a respiratory substrate. Experiments in which ascorbate was fed to isolated leaf discs also resulted in increased rates of photosynthesis providing strong indication for an ascorbate-mediated link between the energy-generating processes of respiration and photosynthesis. This report thus shows that the repression of this mitochondrially localized enzyme improves both carbon assimilation and aerial growth in a crop species. PMID:15665243

  8. Activating HSP72 in Rodent Skeletal Muscle Increases Mitochondrial Number and Oxidative Capacity and Decreases Insulin Resistance

    PubMed Central

    Henstridge, Darren C.; Bruce, Clinton R.; Drew, Brian G.; Tory, Kálmán; Kolonics, Attila; Estevez, Emma; Chung, Jason; Watson, Nadine; Gardner, Timothy; Lee-Young, Robert S.; Connor, Timothy; Watt, Matthew J.; Carpenter, Kevin; Hargreaves, Mark; McGee, Sean L.; Hevener, Andrea L.; Febbraio, Mark A.

    2014-01-01

    Induction of heat shock protein (HSP)72 protects against obesity-induced insulin resistance, but the underlying mechanisms are unknown. Here, we show that HSP72 plays a pivotal role in increasing skeletal muscle mitochondrial number and oxidative metabolism. Mice overexpressing HSP72 in skeletal muscle (HSP72Tg) and control wild-type (WT) mice were fed either a chow or high-fat diet (HFD). Despite a similar energy intake when HSP72Tg mice were compared with WT mice, the HFD increased body weight, intramuscular lipid accumulation (triacylglycerol and diacylglycerol but not ceramide), and severe glucose intolerance in WT mice alone. Whole-body VO2, fatty acid oxidation, and endurance running capacity were markedly increased in HSP72Tg mice. Moreover, HSP72Tg mice exhibited an increase in mitochondrial number. In addition, the HSP72 coinducer BGP-15, currently in human clinical trials for type 2 diabetes, also increased mitochondrial number and insulin sensitivity in a rat model of type 2 diabetes. Together, these data identify a novel role for activation of HSP72 in skeletal muscle. Thus, the increased oxidative metabolism associated with activation of HSP72 has potential clinical implications not only for type 2 diabetes but also for other disorders where mitochondrial function is compromised. PMID:24430435

  9. The Magnetic Free Energy in Active Regions

    NASA Technical Reports Server (NTRS)

    Metcalf, Thomas R.; Mickey, Donald L.; LaBonte, Barry J.

    2001-01-01

    The magnetic field permeating the solar atmosphere governs much of the structure, morphology, brightness, and dynamics observed on the Sun. The magnetic field, especially in active regions, is thought to provide the power for energetic events in the solar corona, such as solar flares and Coronal Mass Ejections (CME) and is believed to energize the hot coronal plasma seen in extreme ultraviolet or X-rays. The question remains what specific aspect of the magnetic flux governs the observed variability. To directly understand the role of the magnetic field in energizing the solar corona, it is necessary to measure the free magnetic energy available in active regions. The grant now expiring has demonstrated a new and valuable technique for observing the magnetic free energy in active regions as a function of time.

  10. Modification of carbonic anhydrase II with acetaldehyde, the first metabolite of ethanol, leads to decreased enzyme activity

    PubMed Central

    Bootorabi, Fatemeh; Jänis, Janne; Valjakka, Jarkko; Isoniemi, Sari; Vainiotalo, Pirjo; Vullo, Daniela; Supuran, Claudiu T; Waheed, Abdul; Sly, William S; Niemelä, Onni; Parkkila, Seppo

    2008-01-01

    Background Acetaldehyde, the first metabolite of ethanol, can generate covalent modifications of proteins and cellular constituents. However, functional consequences of such modification remain poorly defined. In the present study, we examined acetaldehyde reaction with human carbonic anhydrase (CA) isozyme II, which has several features that make it a suitable target protein: It is widely expressed, its enzymatic activity can be monitored, its structural and catalytic properties are known, and it contains 24 lysine residues, which are accessible sites for aldehyde reaction. Results Acetaldehyde treatment in the absence and presence of a reducing agent (NaBH3(CN)) caused shifts in the pI values of CA II. SDS-PAGE indicated a shift toward a slightly higher molecular mass. High-resolution mass spectra of CA II, measured with and without NaBH3(CN), indicated the presence of an unmodified protein, as expected. Mass spectra of CA II treated with acetaldehyde revealed a modified protein form (+26 Da), consistent with a "Schiff base" formation between acetaldehyde and one of the primary NH2 groups (e.g., in lysine side chain) in the protein structure. This reaction was highly specific, given the relative abundance of over 90% of the modified protein. In reducing conditions, each CA II molecule had reacted with 9–19 (14 on average) acetaldehyde molecules (+28 Da), consistent with further reduction of the "Schiff bases" to substituted amines (N-ethyllysine residues). The acetaldehyde-modified protein showed decreased CA enzymatic activity. Conclusion The acetaldehyde-derived modifications in CA II molecule may have physiological consequences in alcoholic patients. PMID:19036170

  11. 19-Substituted Benzoquinone Ansamycin Heat Shock Protein-90 Inhibitors: Biological Activity and Decreased Off-Target Toxicity

    PubMed Central

    Chang, Chuan-Hsin; Drechsel, Derek A.; Kitson, Russell R. A.; Siegel, David; You, Qiang; Backos, Donald S.; Ju, Cynthia; Moody, Christopher J.

    2014-01-01

    The benzoquinone ansamycins (BQAs) are a valuable class of antitumor agents that serve as inhibitors of heat shock protein (Hsp)-90. However, clinical use of BQAs has resulted in off-target toxicities, including concerns of hepatotoxicity. Mechanisms underlying the toxicity of quinones include their ability to redox cycle and/or arylate cellular nucleophiles. We have therefore designed 19-substituted BQAs to prevent glutathione conjugation and nonspecific interactions with protein thiols to minimize off-target effects and reduce hepatotoxicity. 19-Phenyl– and 19-methyl–substituted versions of geldanamycin and its derivatives, 17-allylamino-17-demethoxygeldanamycin and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), did not react with glutathione, whereas marked reactivity was observed using parent BQAs. Importantly, although 17-DMAG induced cell death in primary and cultured mouse hepatocytes, 19-phenyl and 19-methyl DMAG showed reduced toxicity, validating the overall approach. Furthermore, our data suggest that arylation reactions, rather than redox cycling, are a major mechanism contributing to BQA hepatotoxicity. 19-Phenyl BQAs inhibited purified Hsp90 in a NAD(P)H:quinone oxidoreductase 1 (NQO1)–dependent manner, demonstrating increased efficacy of the hydroquinone ansamycin relative to its parent quinone. Molecular modeling supported increased stability of the hydroquinone form of 19-phenyl-DMAG in the active site of human Hsp90. In human breast cancer cells, 19-phenyl BQAs induced growth inhibition also dependent upon metabolism via NQO1 with decreased expression of client proteins and compensatory induction of Hsp70. These data demonstrate that 19-substituted BQAs are unreactive with thiols, display reduced hepatotoxicity, and retain Hsp90 and growth-inhibitory activity in human breast cancer cells, although with diminished potency relative to parent BQAs. PMID:24682466

  12. Short-term oral exposure to aluminium decreases glutathione intestinal levels and changes enzyme activities involved in its metabolism.

    PubMed

    Orihuela, Daniel; Meichtry, Verónica; Pregi, Nicolás; Pizarro, Manuel

    2005-09-01

    To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days. Controls received deionized water. At doses above 120 mg/kg b.w., Al produced both a significant reduction of GSH content and an increase of oxidized/reduced glutathione ratio (P < 0.05). The index of oxidative stress of the intestine mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances was significantly increased (52%) at higher Al dose used. The duodenal expression of the multidrug resistance-associated protein 2 in brush border membranes, determined by Western blot technique, was increased 2.7-fold in rats treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH-synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were significantly reduced (26% and 31%, respectively) while glutathione-S-transferase showed to be slightly modified in the Al-treated groups. Conversely, gamma-glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A positive linear correlation between the intestine GSH depletion and reduction of in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P = 0.038). Taking as a whole, these results show that Al would alter GSH metabolism in small intestine by decreasing its turnover, leading to an unbalance of redox state in the epithelial cells, thus contributing to deteriorate GSH-dependent absorptive functions. PMID:16084594

  13. Short-term oral exposure to aluminium decreases glutathione intestinal levels and changes enzyme activities involved in its metabolism.

    PubMed

    Orihuela, Daniel; Meichtry, Verónica; Pregi, Nicolás; Pizarro, Manuel

    2005-09-01

    To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days. Controls received deionized water. At doses above 120 mg/kg b.w., Al produced both a significant reduction of GSH content and an increase of oxidized/reduced glutathione ratio (P < 0.05). The index of oxidative stress of the intestine mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances was significantly increased (52%) at higher Al dose used. The duodenal expression of the multidrug resistance-associated protein 2 in brush border membranes, determined by Western blot technique, was increased 2.7-fold in rats treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH-synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were significantly reduced (26% and 31%, respectively) while glutathione-S-transferase showed to be slightly modified in the Al-treated groups. Conversely, gamma-glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A positive linear correlation between the intestine GSH depletion and reduction of in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P = 0.038). Taking as a whole, these results show that Al would alter GSH metabolism in small intestine by decreasing its turnover, leading to an unbalance of redox state in the epithelial cells, thus contributing to deteriorate GSH-dependent absorptive functions.

  14. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment.

    PubMed

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-03-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with 'psychoticism', a trait associated with a lack of empathic concern and antisocial tendencies, and with 'need for cognition', a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others.

  15. Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats

    NASA Astrophysics Data System (ADS)

    Thorling, Camilla A.; Liu, Xin; Burczynski, Frank J.; Fletcher, Linda M.; Gobe, Glenda C.; Roberts, Michael S.

    2011-11-01

    Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery. In orthotopic transplantation, the donor liver is exposed to periods of ischemia and when oxygenated blood is reintroduced to the liver, oxidative stress may develop and lead to graft failure. The aim of this project was to investigate whether noninvasive multiphoton and fluorescence lifetime imaging microscopy, without external markers, were useful in detecting early liver damage caused by I/R injury. Localized hepatic ischemia was induced in rats for 1 h followed by 4 h reperfusion. Multiphoton and fluorescence lifetime imaging microscopy was conducted prior to ischemia and up to 4 h of reperfusion and compared to morphological and biochemical assessment of liver damage. Liver function was significantly impaired at 2 and 4 h of reperfusion. Multiphoton microscopy detected liver damage at 1 h of reperfusion, manifested by vacuolated cells and heterogeneous spread of damage over the liver. The damage was mainly localized in the midzonal region of the liver acinus. In addition, fluorescence lifetime imaging showed a decrease in cellular metabolic activity. Multiphoton and fluorescence lifetime imaging microscopy detected evidence of early I/R injury both structurally and functionally. This provides a simple noninvasive technique useful for following progressive liver injury without external markers.

  16. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment

    PubMed Central

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-01-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with ‘psychoticism’, a trait associated with a lack of empathic concern and antisocial tendencies, and with ‘need for cognition’, a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  17. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment.

    PubMed

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-03-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with 'psychoticism', a trait associated with a lack of empathic concern and antisocial tendencies, and with 'need for cognition', a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  18. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura.

    PubMed

    Peerschke, Ellinor I B; Andemariam, Biree; Yin, Wei; Bussel, James B

    2010-02-01

    The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 x 10(9)/l) (P = 0.027) and thrombocytopenia (platelet count < 100 x 10(9)/l) (P = 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes. PMID:19925495

  19. Energy Expenditure During Extravehicular Activity Through Apollo

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.

    2012-01-01

    Monitoring crew health during manned space missions has always been an important factor to ensure that the astronauts can complete the missions successfully and within safe physiological limits. The necessity of real-time metabolic rate monitoring during extravehicular activities (EVAs) came into question during the Gemini missions, when the energy expenditure required to complete EVA tasks exceeded the life support capabilities for cooling and humidity control and, as a result, crew members ended the EVAs fatigued and overworked. This paper discusses the importance of real-time monitoring of metabolic rate during EVAs, and provides a historical look at energy expenditure during EVAs through the Apollo Program.

  20. Energy Expenditure During Extravehicular Activity Through Apollo

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.

    2011-01-01

    Monitoring crew health during manned space missions has always been an important factor to ensure that the astronauts can complete the missions successfully and within safe physiological limits. The necessity of real-time metabolic rate monitoring during extravehicular activities (EVAs) came into question during the Gemini missions, when the energy expenditure required to complete EVA tasks exceeded the life support capabilities for cooling and humidity control and crewmembers (CMs) ended the EVAs fatigued and overworked. This paper discusses the importance of real-time monitoring of metabolic rate during EVA, and provides a historical look at energy expenditure during EVA through the Apollo program.

  1. Combined effects of short-term exposure to elevated CO2 and decreased O2 on the physiology and energy budget of the thick shell mussel Mytilus coruscus.

    PubMed

    Sui, Yanming; Kong, Hui; Huang, Xizhi; Dupont, Sam; Hu, Menghong; Storch, Daniela; Pörtner, Hans-Otto; Lu, Weiqun; Wang, Youji

    2016-07-01

    Hypoxia and ocean acidification are two consequences of anthropogenic activities. These global trends occur on top of natural variability. In environments such as estuarine areas, short-term acute pH and O2 fluctuations are occurring simultaneously. The present study tested the combined effects of short-term seawater acidification and hypoxia on the physiology and energy budget of the thick shell mussel Mytilus coruscus. Mussels were exposed for 72 h to six combined treatments with three pH levels (8.1, 7.7 and 7.3) and two dissolved oxygen (DO) levels (2 mg L(-1), 6 mg L(-1)). Clearance rate (CR), food absorption efficiency (AE), respiration rate (RR), ammonium excretion rate (ER), O:N ratio and scope for growth (SFG) were significantly reduced, and faecal organic dry weight ratio (E) was significantly increased at low DO. Low pH did not lead to a reduced SFG. Interactive effects of pH and DO were observed for CR, E and RR. Principal component analysis (PCA) revealed positive relationships among most physiological indicators, especially between SFG and CR under normal DO conditions. These results demonstrate that Mytilus coruscus was sensitive to short-term (72 h) exposure to decreased O2 especially if combined with decreased pH levels. In conclusion, the short-term oxygen and pH variation significantly induced physiological changes of mussels with some interactive effects. PMID:27115845

  2. Get Current: Switch on Clean Energy Activity Book

    SciTech Connect

    2014-06-01

    Switching on clean energy technologies means strengthening the economy while protecting the environment. This activity book for all ages promotes energy awareness, with facts on different types of energy and a variety of puzzles in an energy theme.

  3. Active Control by Conservation of Energy Concept

    NASA Technical Reports Server (NTRS)

    Maestrello, Lucio

    2000-01-01

    Three unrelated experiments are discussed; each was extremely sensitive to initial conditions. The initial conditions are the beginnings of the origins of the information that nonlinearity displays. Initial conditions make the phenomenon unstable and unpredictable. With the knowledge of the initial conditions, active control requires far less power than that present in the system response. The first experiment is on the control of shocks from an axisymmetric supersonic jet; the second, control of a nonlinear panel response forced by turbulent boundary layer and sound; the third, control of subharmonic and harmonics of a panel forced by sound. In all three experiments, control is achieved by redistribution of periodic energy response such that the energy is nearly preserved from a previous uncontrolled state. This type of active control improves the performance of the system being controlled.

  4. Bamboo Vinegar Decreases Inflammatory Mediator Expression and NLRP3 Inflammasome Activation by Inhibiting Reactive Oxygen Species Generation and Protein Kinase C-α/δ Activation

    PubMed Central

    Ka, Shuk-Man; Chen, Ann; Tasi, Yu-Ling; Liu, May-Lan; Chiu, Yi-Chich; Hua, Kuo-Feng

    2013-01-01

    Bamboo vinegar (BV), a natural liquid derived from the condensation produced during bamboo charcoal production, has been used in agriculture and as a food additive, but its application to immune modulation has not been reported. Here, we demonstrated that BV has anti-inflammatory activities both in vitro and in vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide levels in, and interleukin-6 secretion by, lipopolysaccharide-activated macrophages without affecting tumor necrosis factor-α secretion and cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV involved decreased reactive oxygen species production and protein kinase C-α/δ activation. Furthermore, creosol (2-methoxy-4-methylphenol) was indentified as the major anti-inflammatory compound in BV. Impaired cytokine expression and NLR family, pyrin domain-containing 3 (NLRP3) inflammasome activation was seen in mice treated with creosol. These findings provide insights into how BV regulates inflammation and suggest that it may be a new source for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation- and NLRP3 inflammasome-related diseases, including metabolic syndrome. PMID:24124509

  5. Optogenetic activation of GABAergic neurons in the nucleus accumbens decreases the activity of the ventral pallidum and the expression of cocaine-context-associated memory.

    PubMed

    Wang, Li; Shen, Minjie; Yu, Yongchun; Tao, Yezheng; Zheng, Ping; Wang, Feifei; Ma, Lan

    2014-05-01

    GABAergic medium-sized spiny neurons (MSNs) in the nucleus accumbens (NAc) differentially express D1 and D2 dopamine receptors. Both D2- and D1-MSNs in the NAc form projections into the ventral pallidum, whereas only D1-MSNs directly project into midbrain neurons. They are critical in rewarding and aversive learning, and understanding the function of these NAc efferents and the alteration of their targeted brain regions in responding to a reward-associated context is important. In this study, we activated the GABAergic neurons in the NAc of mice expressing channelrhodopsin-2 under the control of the vesicular GABA transporter promoter by an optogenetic approach, and examined its effects on the expression of cocaine-context-associated memory. In vivo optogenetic activation of the NAc GABAergic neurons inhibited the expression of cocaine-conditioned place preference (CPP). When tested 24 h later, these mice exhibited normal cocaine-induced CPP, indicating that the inhibitory effect on the expression of CPP was transient and reversible. Activation of the NAc GABAergic neurons also attenuated the learning of cocaine-induced reinforcement, as indicated by the results of behavioural sensitization. To explore how the cocaine-context-associated information was processed and integrated, we assessed the activity of NAc MSN-targeted brain nuclei and found that the activation of NAc GABAergic neurons during CPP expression resulted in a decrease of c-Fos+ cells in the ventral palladium. Our data suggested that the NAc GABAergic efferents inhibit the ventral palladium activity and negatively regulate the expression of motivational effects induced by cocaine-context-associated cues.

  6. A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period.

    PubMed

    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tatsuta, Tomohiro; Morita, Yoshio; Takemura, Motohiko

    2012-01-01

    Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decreases, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naïve male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments. PMID:22079320

  7. A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period.

    PubMed

    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tatsuta, Tomohiro; Morita, Yoshio; Takemura, Motohiko

    2012-01-01

    Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decreases, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naïve male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments.

  8. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptos...

  9. Energy and Man's Environment Activity Guide: An Interdisciplinary Teacher's Guide to Energy and Environmental Activities, Section One - Sources of Energy.

    ERIC Educational Resources Information Center

    Jones, John, Ed.

    This publication presents the activities pertaining to the first goal of this activity guide series. The activities in this publication focus primarily on the availability of resources, forms of energy, natural laws, and socioeconomic considerations. These materials are appropriate for middle school and junior high school students. These…

  10. Energy Adventure Center. Activity Book. Revised [and Expanded] Edition.

    ERIC Educational Resources Information Center

    Wichita Unified School District 259, KS.

    A variety of energy activities are provided, including instructions for and questions related to energy films. The activities are organized into five sections. Section 1 (work) includes an activity focusing on movement and change. Section 2 (forms of energy) includes activities related to mechanical (movement), radiant (light), chemical (burning),…

  11. MAGNETIC ENERGY SPECTRA IN SOLAR ACTIVE REGIONS

    SciTech Connect

    Abramenko, Valentyna; Yurchyshyn, Vasyl

    2010-09-01

    Line-of-sight magnetograms for 217 active regions (ARs) with different flare rates observed at the solar disk center from 1997 January until 2006 December are utilized to study the turbulence regime and its relationship to flare productivity. Data from the SOHO/MDI instrument recorded in the high-resolution mode and data from the BBSO magnetograph were used. The turbulence regime was probed via magnetic energy spectra and magnetic dissipation spectra. We found steeper energy spectra for ARs with higher flare productivity. We also report that both the power index, {alpha}, of the energy spectrum, E(k) {approx} k{sup -}{alpha}, and the total spectral energy, W = {integral}E(k)dk, are comparably correlated with the flare index, A, of an AR. The correlations are found to be stronger than those found between the flare index and the total unsigned flux. The flare index for an AR can be estimated based on measurements of {alpha} and W as A = 10{sup b}({alpha}W){sup c}, with b = -7.92 {+-} 0.58 and c = 1.85 {+-} 0.13. We found that the regime of the fully developed turbulence occurs in decaying ARs and in emerging ARs (at the very early stage of emergence). Well-developed ARs display underdeveloped turbulence with strong magnetic dissipation at all scales.

  12. ERP Energy and Cognitive Activity Correlates

    NASA Astrophysics Data System (ADS)

    Schillaci, Michael Jay; Vendemia, Jennifer M. C.

    2014-03-01

    We propose a novel analysis approach for high-density event related scalp potential (ERP) data where the integrated channel-power is used to attain an energy density functional state for channel-clusters of neurophysiological significance. The method is applied to data recorded during a two-stimulus, directed lie paradigm and shows that deceptive responses emit between 8% and 10% less power. A time course analysis of these cognitive activity measures over posterior and anterior regions of the cortex suggests that neocortical interactions, reflecting the differing workload demands during executive and semantic processes, take about 50% longer for the case of deception. These results suggest that the proposed method may provide a useful tool for the analysis of ERP correlates of high-order cognitive functioning. We also report on a possible equivalence between the energy functional distribution and near-infrared signatures that have been measured with other modalities.

  13. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity.

    PubMed

    Thiesson, Helle C; Jensen, Boye L; Bistrup, Claus; Ottosen, Peter D; McNeilly, Alison D; Andrew, Ruth; Seckl, Jonathan; Skøtt, Ole

    2007-01-01

    Downregulation of the renal glucocorticoid-metabolizing enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) during liver cirrhosis may allow activation of the mineralocorticoid receptor (MR) by glucocorticoids and contribute to sodium retention. We tested this hypothesis in male Wistar rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion, and reduced ascites formation to the same degree as direct inhibition of MR with K-canrenoate. Total potassium balance was negative in the BDL rats, whereas renal potassium excretion was unchanged. In the distal colon, expression of ENaC was increased in BDL rats. Fecal potassium excretion was increased in cirrhotic rats, and this was corrected by treatment with K-canrenoate but not dexamethasone. We conclude that development of sodium retention and decompensation in cirrhotic rats is associated with downregulation of renal 11beta-HSD-2 activity and inappropriate activation of renal sodium reabsorption by endogenous glucocorticoids. In addition, the overall potassium loss in the BDL model is due to increased fecal potassium excretion, which is associated with upregulation of ENaC in distal colon. PMID:16917017

  14. Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.

    PubMed

    Cui, Jiajun; Meng, Xianfeng; Gao, Xudong; Tan, Guangxuan

    2010-03-01

    Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger, anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour cells. To investigate whether curcumin can regulate the expression of Pokemon, a series of experiments were carried out. Transient transfection experiments demonstrated that curcumin could decrease the activity of the Pokemon promoter. Western blot analysis suggested that curcumin could significantly decrease the expression of the Pokemon. Overexpression of Sp1 could enhance the activity of the Pokemon promoter, whereas knockdown of Sp1 could decrease its activity. More important, we also found that curcumin could decrease the expression of the Pokemon by suppressing the stimulation of the Sp1 protein. Therefore, curcumin is a potential reagent for tumour therapy which may target Pokemon. PMID:19444642

  15. Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.

    PubMed

    Cui, Jiajun; Meng, Xianfeng; Gao, Xudong; Tan, Guangxuan

    2010-03-01

    Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger, anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour cells. To investigate whether curcumin can regulate the expression of Pokemon, a series of experiments were carried out. Transient transfection experiments demonstrated that curcumin could decrease the activity of the Pokemon promoter. Western blot analysis suggested that curcumin could significantly decrease the expression of the Pokemon. Overexpression of Sp1 could enhance the activity of the Pokemon promoter, whereas knockdown of Sp1 could decrease its activity. More important, we also found that curcumin could decrease the expression of the Pokemon by suppressing the stimulation of the Sp1 protein. Therefore, curcumin is a potential reagent for tumour therapy which may target Pokemon.

  16. Hydrogen Energy Storage (HES) Activities at NREL; NREL (National Renewable Energy Laboratory)

    SciTech Connect

    Eichman, J.

    2015-04-21

    This presentation provides an overview of hydrogen and energy storage, including hydrogen storage pathways and international power-to-gas activities, and summarizes the National Renewable Energy Laboratory's hydrogen energy storage activities and results.

  17. Elevated venous glutamate levels in (pre)catabolic conditions result at least partly from a decreased glutamate transport activity.

    PubMed

    Hack, V; Stütz, O; Kinscherf, R; Schykowski, M; Kellerer, M; Holm, E; Dröge, W

    1996-06-01

    Abnormally high postabsorptive venous plasma glutamate levels have been reported for several diseases that are associated with a loss of body cell mass including cancer, human/simian immunodeficiency virus infection, and amyotrophic lateral sclerosis. Studies on exchange rates in well-nourished cancer patients now show that high venous plasma glutamate levels may serve as a bona fide indicator for a decreased uptake of glutamate by the peripheral muscle tissue in the postabsorptive period and may be indicative for a precachectic state. High glutamate levels are also moderately correlated with a decreased uptake of glucose and ketone bodies. Relatively high venous glutamate levels have also been found in non-insulin-dependent diabetes mellitus and to some extent also in the cubital vein of normal elderly subjects, i.e., in conditions commonly associated with a decreased glucose tolerance and progressive loss of body cell mass.

  18. Rationale, design and methods for a randomised and controlled trial to investigate whether home access to electronic games decreases children's physical activity

    PubMed Central

    Straker, Leon M; Abbott, Rebecca A; Piek, Jan P; Pollock, Clare M; Davies, Peter S; Smith, Anne J

    2009-01-01

    Background Many children are reported to have insufficient physical activity (PA) placing them at greater risk of poor health outcomes. Participating in sedentary activities such as playing electronic games is widely believed to contribute to less PA. However there is no experimental evidence that playing electronic games reduces PA. There is also no evidence regarding the effect of different types of electronic games (traditional sedentary electronic games versus new active input electronic games) on PA. Further, there is a poor understanding about how characteristics of children may moderate the impact of electronic game access on PA and about what leisure activities are displaced when children play electronic games. Given that many children play electronic games, a better understanding of the effect of electronic game use on PA is critical to inform child health policy and intervention. Methods This randomised and controlled trial will examine whether PA is decreased by access to electronic games and whether any effect is dependent on the type of game input or the child's characteristics. Children aged 10–12 years (N = 72, 36 females) will be recruited and randomised to a balanced ordering of 'no electronic games', 'traditional' electronic games and 'active' electronic games. Each child will participate in each condition for 8 weeks, and be assessed prior to participation and at the end of each condition. The primary outcome is PA, assessed by Actical accelerometers worn for 7 days on the wrist and hip. Energy expenditure will be assessed by the doubly labelled water technique and motor coordination, adiposity, self-confidence, attitudes to technology and PA and leisure activities will also be assessed. A sample of 72 will provide a power of > 0.9 for detecting a 15 mins difference in PA (sd = 30 mins). Discussion This is the first such trial and will provide critical information to understand whether access to electronic games affects children's PA. Given the

  19. Capsaicin, nonivamide and trans-pellitorine decrease free fatty acid uptake without TRPV1 activation and increase acetyl-coenzyme A synthetase activity in Caco-2 cells.

    PubMed

    Rohm, Barbara; Riedel, Annett; Ley, Jakob P; Widder, Sabine; Krammer, Gerhard E; Somoza, Veronika

    2015-01-01

    Red pepper and its major pungent component, capsaicin, have been associated with hypolipidemic effects in rats, although mechanistic studies on the effects of capsaicin and/or structurally related compounds on lipid metabolism are scarce. In this work, the effects of capsaicin and its structural analog nonivamide, the aliphatic alkamide trans-pellitorine and vanillin as the basic structural element of all vanilloids on the mechanisms of intestinal fatty acid uptake in differentiated intestinal Caco-2 cells were studied. Capsaicin and nonivamide were found to reduce fatty acid uptake, with IC₅₀ values of 0.49 μM and 1.08 μM, respectively. trans-Pellitorine was shown to reduce fatty acid uptake by 14.0±2.14% at 100 μM, whereas vanillin was not effective, indicating a pivotal role of the alkyl chain with the acid amide group in fatty acid uptake by Caco-2 cells. This effect was associated neither with the activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or the epithelial sodium channel (ENaC) nor with effects on paracellular transport or glucose uptake. However, acetyl-coenzyme A synthetase activity increased (p<0.05) in the presence of 10 μM capsaicin, nonivamide or trans-pellitorine, pointing to an increased fatty acid biosynthesis that might counteract the decreased fatty acid uptake.

  20. Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjögren's syndrome and systemic lupus erythematosus

    PubMed Central

    Sellam, Jérémie; Miceli‐Richard, Corinne; Gottenberg, Jacques‐Eric; Ittah, Marc; Lavie, Frédéric; Lacabaratz, Christine; Gestermann, Nicolas; Proust, Alexis; Lambotte, Olivier

    2007-01-01

    Objective To analyse B cell activating factor (BAFF) receptor (BAFF‐R) expression on peripheral lymphocytes from patients with primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Patients and methods Peripheral blood mononuclear cells from 20 patients with pSS, 19 patients with SLE and 15 controls were examined by flow cytometry to investigate BAFF‐R mean fluorescence intensity (MFI) on lymphocytes. BAFF‐R mRNA level from isolated blood B cells of nine patients with pSS and eight controls was assessed by real‐time quantitative reverse transcription‐PCR. BAFF serum level was determined by ELISA. Results In all subjects, BAFF‐R was expressed on all naïve CD27− and memory CD27+ B‐cells and was present on <0.5% of T cells. The expression of BAFF‐R on B cells was significantly decreased in patients with pSS as compared with controls (MFI = 7.8 vs 10.6, p = 0.001), and was intermediate in patients with SLE (MFI = 9.5). Serum BAFF level was inversely correlated with BAFF‐R MFI (p = 0.007), but not because of competition between endogenous BAFF (at observed concentrations in patients) and the monoclonal antibody (11C1) detecting BAFF‐R. BAFF‐R mRNA levels did not differ between patients with pSS and controls (p = 0.48). BAFF‐R MFI decreased after overnight culture with recombinant human BAFF (from 32.5 to 25.4, p = 0.03). Contrary to the serum BAFF level, BAFF‐R expression was correlated with extraglandular involvement in pSS and SLE Disease Activity Index. Conclusions BAFF‐R expression is reduced on peripheral B cells of patients with pSS and SLE. This down‐regulation occurs through a post‐transcriptional mechanism and could be the consequence of chronic increase in BAFF. BAFF‐R levels on B cells could be a novel activity biomarker in autoimmune diseases. PMID:17185325

  1. Activation of epidermal growth factor receptor by metal-ligand complexes decreases levels of extracellular amyloid beta peptide.

    PubMed

    Price, Katherine A; Filiz, Gulay; Caragounis, Aphrodite; Du, Tai; Laughton, Katrina M; Masters, Colin L; Sharples, Robyn A; Hill, Andrew F; Li, Qiao-Xin; Donnelly, Paul S; Barnham, Kevin J; Crouch, Peter J; White, Anthony R

    2008-01-01

    The epidermal growth factor receptor is a receptor tyrosine kinase expressed in a range of tissues and cell-types. Activation of the epidermal growth factor receptor by a number of ligands induces downstream signalling that modulates critical cell functions including growth, survival and differentiation. Abnormal epidermal growth factor receptor expression and activation is also involved in a number of cancers. In addition to its cognate ligands, the epidermal growth factor receptor can be activated by metals such as zinc (Zn) and copper (Cu). Due to the important role of these metals in a number of diseases including neurodegenerative disorders, therapeutic approaches are being developed based on the use of lipid permeable metal-complexing molecules. While these agents are showing promising results in animal models and clinical trials, little is known about the effects of metal-ligand complexes on cell signalling pathways. In this study, we investigated the effects of clioquinol (CQ)-metal complexes on activation of epidermal growth factor receptor. We show here that CQ-Cu complexes induced potent epidermal growth factor receptor phosphorylation resulting in downstream activation of extracellular signal-regulated kinase. Similar levels of epidermal growth factor receptor activation were observed with alternative lipid permeable metal-ligands including neocuproine and pyrrolidine dithiocarbamate. We found that CQ-Cu complexes induced a significant reduction in the level of extracellular Abeta1-40 in cell culture. Inhibition of epidermal growth factor receptor activation by PD153035 blocked extracellular signal-regulated kinase phosphorylation and restored Abeta1-40 levels. Activation of the epidermal growth factor receptor by CQ-Cu was mediated through up-regulation of src kinase activity by a cognate ligand-independent process involving membrane integrins. These findings provide the first evidence that metal-ligand complexes can activate the epidermal growth

  2. Activity pattern and energy expenditure due to physical activity before and during pregnancy in healthy Swedish women.

    PubMed

    Lof, Marie; Forsum, Elisabet

    2006-02-01

    Human pregnancy is associated with increased requirements for dietary energy and this increase may be partly offset by reductions in physical activity during gestation. Studies in well-nourished women have shown that the physical activity level (PAL), obtained as the total energy expenditure (TEE) divided by the BMR, decreases in late pregnancy. However, it is not known if this decrease is really caused by reductions in physical activity or if it is the result of decreases in energy expenditure/BMR (the so-called metabolic equivalent, MET) for many activities in late pregnancy. In the present study activity pattern, TEE and BMR were assessed in twenty-three healthy Swedish women before pregnancy as well as in gestational weeks 14 and 32. Activity pattern was assessed using a questionnaire and heart rate recording. TEE was assessed using the doubly labelled water method and BMR was measured by means of indirect calorimetry. When compared to the pre-pregnant value, there was little change in the PAL in gestational week 14 but it was significantly reduced in gestational week 32. Results obtained by means of the questionnaire and by heart rate recording showed that the activity pattern was largely unaffected by pregnancy. The findings support the following conclusion: in a population of well-nourished women where the activity pattern is maintained during pregnancy, the increase in BMR represents approximately the main part of the pregnancy-induced increase in TEE, at least until gestational week 32.

  3. Ageing Is Associated with Decreases in Appetite and Energy Intake—A Meta-Analysis in Healthy Adults

    PubMed Central

    Giezenaar, Caroline; Chapman, Ian; Luscombe-Marsh, Natalie; Feinle-Bisset, Christine; Horowitz, Michael; Soenen, Stijn

    2016-01-01

    It is not well recognized that in the elderly weight loss is more common than weight gain. The aim of this analysis was to determine the effect of ageing on appetite (hunger/fullness) and energy intake, after overnight fasting and in a postprandial state, by meta-analyses of trials that included at least two age groups (>18 years). We hypothesized that appetite and energy intake would be less in healthy older compared with younger adults. Following a PubMed-database systematic search up to 30 June 2015, 59 studies were included in the random-effects-model meta-analyses. Energy intake was 16%–20% lower in older (n = 3574/~70 years/~71 kg/~25 kg/m2) than younger (n = 4111/~26 years/~69 kg/~23 kg/m2) adults (standardized mean difference: −0.77 (95% confidence interval −0.90 to −0.64)). Hunger was 25% (after overnight fasting; weighted mean difference (WMD): −17 (−22 to −13) mm) to 39% (in a postprandial state; WMD: −14 (−19 to −9) mm) lower, and fullness 37% (after overnight fasting; WMD: 6 mm (95% CI: 1 to 11 mm)) greater in older than younger adults. In conclusion, appetite and energy intake are less in healthy older than younger adults, suggesting that ageing per se affects food intake. PMID:26751475

  4. Ageing Is Associated with Decreases in Appetite and Energy Intake--A Meta-Analysis in Healthy Adults.

    PubMed

    Giezenaar, Caroline; Chapman, Ian; Luscombe-Marsh, Natalie; Feinle-Bisset, Christine; Horowitz, Michael; Soenen, Stijn

    2016-01-07

    It is not well recognized that in the elderly weight loss is more common than weight gain. The aim of this analysis was to determine the effect of ageing on appetite (hunger/fullness) and energy intake, after overnight fasting and in a postprandial state, by meta-analyses of trials that included at least two age groups (>18 years). We hypothesized that appetite and energy intake would be less in healthy older compared with younger adults. Following a PubMed-database systematic search up to 30 June 2015, 59 studies were included in the random-effects-model meta-analyses. Energy intake was 16%-20% lower in older (n = 3574/~70 years/~71 kg/~25 kg/m²) than younger (n = 4111/~26 years/~69 kg/~23 kg/m²) adults (standardized mean difference: -0.77 (95% confidence interval -0.90 to -0.64)). Hunger was 25% (after overnight fasting; weighted mean difference (WMD): -17 (-22 to -13) mm) to 39% (in a postprandial state; WMD: -14 (-19 to -9) mm) lower, and fullness 37% (after overnight fasting; WMD: 6 mm (95% CI: 1 to 11 mm)) greater in older than younger adults. In conclusion, appetite and energy intake are less in healthy older than younger adults, suggesting that ageing per se affects food intake.

  5. Platelet activation and platelet-monocyte aggregate formation contribute to decreased platelet count during acute simian immunodeficiency virus infection in pig-tailed macaques.

    PubMed

    Metcalf Pate, Kelly A; Lyons, Claire E; Dorsey, Jamie L; Shirk, Erin N; Queen, Suzanne E; Adams, Robert J; Gama, Lucio; Morrell, Craig N; Mankowski, Joseph L

    2013-09-01

    Platelets are key participants in innate immune responses to pathogens. As a decrease in circulating platelet count is one of the initial hematologic indicators of human immunodeficiency virus (HIV) infection, we sought to determine whether decline in platelet number during acute infection results from decreased production, increased antibody-mediated destruction, or increased platelet activation in a simian immunodeficiency virus (SIV)/macaque model. During acute SIV infection, circulating platelets were activated with increased surface expression of P-selection, CD40L and major histocompatibility complex class I. Platelet production was maintained and platelet autoantibodies were not detected during acute infection. Concurrent with a decrease in platelet numbers and an increase in circulating monocytes, platelets were found sequestered in platelet-monocyte aggregates, thereby contributing to the decline in platelet counts. Because the majority of circulating CD16(+) monocytes formed complexes with platelets during acute SIV infection, a decreased platelet count may represent platelet participation in the innate immune response to HIV.

  6. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

    PubMed

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

    2016-06-01

    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver.

  7. Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children.

    PubMed

    Smuts, Cornelius M; Greeff, Jani; Kvalsvig, Jane; Zimmermann, Michael B; Baumgartner, Jeannine

    2015-01-28

    Both Fe deficiency and poor n-3 fatty acid status have been associated with behavioural changes in children. In the present study, we investigated the effects of Fe and DHA+EPA supplementation, alone or in combination, on physical activity during school days and on teacher-rated behaviour in healthy Fe-deficient school children. In a 2 × 2 factorial design, children (n 98, 6-11 years) were randomly assigned to receive (1) Fe (50 mg) plus DHA (420 mg)+EPA (80 mg), (2) Fe plus placebo, (3) placebo plus DHA+EPA or (4) placebo plus placebo as oral supplements (4 d/week) for 8.5 months. Physical activity was measured during four school days at baseline and endpoint using accelerometers, and data were stratified into morning class time (08.00-10.29 hours), break time (10.30-11.00 hours) and after-break class time (11.01-12.00 hours) for analysis. Classroom behaviour was assessed at endpoint using Conners' Teacher Rating Scales. DHA+EPA supplementation decreased physical activity counts during morning class time, increased sedentary physical activity, and decreased light- and moderate-intensity physical activities. Consistently, DHA+EPA supplementation increased sedentary physical activity and decreased light-intensity physical activity during after-break class time. Even though there were no treatment effects found on teacher-rated behaviour, lower physical activity during morning class time was associated with lower levels of teacher-rated hyperactivity and oppositional behaviour at endpoint. Despite a positive association between Fe status and physical activity during break time at baseline, Fe supplementation did not affect physical activity during break time and class time. Our findings suggest that DHA+EPA supplementation may decrease physical activity levels during class time, and further indicate that accelerometry might be a useful tool to assess classroom behaviour in healthy children.

  8. Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

    PubMed Central

    Qi, Xin; Du, Xin; Yang, Yongxin; Du, Guijin; Gao, Peihong; Zhang, Yang; Qin, Wen; Li, Xiaodong; Zhang, Quan

    2015-01-01

    Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with internet gaming disorder (IGD), which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs) without IGD were recruited, and the balloon analog risk task (BART) was used in a functional magnetic resonance imaging experiment to evaluate the modulation of the risk level (the probability of balloon explosion) on brain activity during risky decision making in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC) during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11) scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents. PMID:26578922

  9. 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice.

    PubMed

    Ferraz-de-Paula, V; Ribeiro, A; Souza-Queiroz, J; Pinheiro, M L; Vecina, J F; Souza, D P M; Quinteiro-Filho, W M; Moreau, R L M; Queiroz, M L S; Palermo-Neto, J

    2014-12-01

    Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFκB expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-γ, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFκB signaling, being mediated by HPA axis activity and corticosterone.

  10. Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Risk in Streptozotocin-Induced Diabetic Guinea Pigs.

    PubMed

    Aslan, Mutay; Ozcan, Filiz; Kucuksayan, Ertan

    2013-01-01

    This study aimed to investigate LDL subfraction distribution as well as serum cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and paraoxonase (PON1) activity in streptozotocin-induced diabetic guinea pigs. Materials/Methods. Guinea pigs were given a single intraperitoneal (ip) injection of streptozotocin (STZ) and animals having fasting blood glucose levels greater than 200 mg/dl, were considered diabetic. Protein levels of LCAT and CETP were determined via ELISA. Paraoxonase activity was measured kinetically by the formation of phenol while LDL subfraction analysis was done by disc polyacrylamide gel electrophoresis. Results. Plasma glucose and high-density lipoprotein (HDL) cholesterol were significantly increased while total cholesterol and LDL cholesterol were significantly decreased in diabetic guinea pigs compared to controls. LDL subfraction analysis revealed a significant decrease in nonatherogenic LDL-2 subfraction and a significant increase in atherogenic LDL-4 subfraction in diabetic guinea pigs compared to controls. Plasma CETP and PON1 levels were significantly decreased while LCAT showed no significant difference in diabetic guinea pigs compared to controls. Conclusion. Decreased non-atherogenic LDL-1, LDL-2 subfractions, increased small dense LDL-4 subfraction, and decreased PON1 activity, reveals formation of an atherogenic risk in diabetic guinea pigs. Decrease in CETP levels supports the observed increase in HDL cholesterol levels in diabetic guinea pigs. PMID:23691522

  11. Decreased maximal aerobic capacity with use of a triphasic oral contraceptive in highly active women: a randomised controlled trial

    PubMed Central

    Lebrun, C; Petit, M; McKenzie, D; Taunton, J; Prior, J

    2003-01-01

    Background: Oral contraceptives are commonly used by women athletes. However, their effect on athletic performance is unclear. Objectives: To examine the effects of a moderate dose, triphasic oral contraceptive on measures of athletic performance in highly trained women athletes. Methods: This is a double blind, placebo controlled trial in 14 women with ovulatory menstrual cycles and maximal aerobic capacity (VO2MAX) ≥50 ml/kg/min. Four measures of athletic performance were tested: VO2MAX, anaerobic capacity (anaerobic speed test), aerobic endurance (time to fatigue at 90% of VO2MAX), and isokinetic strength (Cybex II dynamometer). Height, weight, and six skinfold measurements were also recorded. All these observational tests were completed during both the follicular and mid-luteal phases of an ovulatory menstrual cycle. Cycle phases were confirmed by assaying plasma oestradiol and progesterone. Participants were subsequently randomly assigned to either a tricyclic oral contraceptive or placebo and retested in identical fashion (oral contraceptive phase). Results: Absolute and relative changes in VO2MAX from follicular to oral contraceptive phase decreased in the oral contraceptive group by 4.7%, whereas the placebo group showed a slight increase (+1.5%) over the same time period. Two of the women taking oral contraceptive had decreases of 4 and 9 ml/kg/min. In contrast, most women in the placebo group improved or maintained VO2MAX. There was also a significant increase in the sum of skinfolds in women taking oral contraceptive compared with those taking placebo (p<0.01). There were no significant changes in other physiological variables (maximum ventilation, heart rate, respiratory exchange ratio, packed cell volume) or measures of performance (anaerobic speed test, aerobic endurance, isokinetic strength) as a function of oral contraceptive treatment. Conclusions: The decrease in VO2MAX that occurs when oral contraceptive is taken may influence elite sporting

  12. The Limit of Free Magnetic Energy in Active Regions

    NASA Technical Reports Server (NTRS)

    Moore, Ron; Falconer, David; Sterling, Alphonse

    2012-01-01

    By measuring from active-region magnetograms a proxy of the free energy in the active region fs magnetic field, it has been found previously that (1) there is an abrupt upper limit to the free energy the field can hold that increases with the amount of magnetic field in the active region, the active region fs magnetic flux content, and (2) the free energy is usually near its limit when the field explodes in a CME/flare eruption. That is, explosive active regions are concentrated in a main-sequence path bordering the free-energy ]limit line in (flux content, free-energy proxy) phase space. Here, from measurement of Marshall Space Flight Center vector magnetograms, we find the magnetic condition that underlies the free ]energy limit and the accompanying main sequence of explosive active regions. Using a suitable free ]energy proxy measured from vector magnetograms of 44 active regions, we find that (1) in active regions at and near their free ]energy limit, the ratio of magnetic-shear free energy to the non ]free magnetic energy the potential field would have is approximately 1 in the core field, the field rooted along the neutral line, and (2) this ratio is progressively less in active regions progressively farther below their free ]energy limit. This shows that most active regions in which this core-field energy ratio is much less than 1 cannot be triggered to explode; as this ratio approaches 1, most active regions become capable of exploding; and when this ratio is 1 or greater, most active regions are compelled to explode. From these results we surmise the magnetic condition that determines the free ]energy limit is the ratio of the free magnetic energy to the non-free energy the active region fs field would have were it completely relaxed to its potential ]field configuration, and that this ratio is approximately 1 at the free-energy limit and in the main sequence of explosive active regions.

  13. Influence of Molting and Starvation on Digestive Enzyme Activities and Energy Storage in Gammarus fossarum

    PubMed Central

    Charron, Laetitia; Geffard, Olivier; Chaumot, Arnaud; Coulaud, Romain; Jaffal, Ali; Gaillet, Véronique; Dedourge-Geffard, Odile; Geffard, Alain

    2014-01-01

    Among the many biological responses studied in ecotoxicology, energy-based biomarkers such as digestive enzyme activities and energy reserves appear to be useful predictive tools for detecting physiological disturbances in organisms. However, the use of these biological responses as biomarkers could be limited by the effects of confounding factors (biotic and abiotic) and physiological processes, such as the reproductive cycle. Thus, the optimal use of these biomarkers will be facilitated by understanding the effects of these factors on the energy metabolism of the sentinel species being studied. We considered abiotic factors (temperature and conductivity) in a previous study, whereas the present study investigated the effects of gender, the female reproductive stage, and food availability on the digestive enzyme activities and energy storage of Gammarus fossarum. The results indicated that, during the female reproductive cycle, the activities of digestive enzymes (amylase, cellulase, and trypsin) decreased significantly, whereas the levels of reserves (proteins, lipids, and sugar) increased until the last premolt stage. Restricted food diets only led to decreased amylase activities in both sexes. Food starvation also induced a decrease in the energy outcomes in females, whereas there were no effects in males. In general, the biochemical (digestive enzyme activities) and physiological (energy reserves) responses were more stable in males than in females. These results support the use of males fed ad libitum to limit the effects of confounding factors when using these energy biomarkers in Gammarus fossarum during biomonitoring programs. PMID:24788197

  14. Minimum daily core body temperature in western grey kangaroos decreases as summer advances: a seasonal pattern, or a direct response to water, heat or energy supply?

    PubMed

    Maloney, Shane K; Fuller, Andrea; Meyer, Leith C R; Kamerman, Peter R; Mitchell, Graham; Mitchell, Duncan

    2011-06-01

    Using implanted temperature loggers, we measured core body temperature in nine western grey kangaroos every 5 min for 24 to 98 days in spring and summer. Body temperature was highest at night and decreased rapidly early in the morning, reaching a nadir at 10:00 h, after ambient temperature and solar radiation had begun to increase. On hotter days, the minimum morning body temperature was lower than on cooler days, decreasing from a mean of 36.2°C in the spring to 34.0°C in the summer. This effect correlated better with the time of the year than with proximate thermal stressors, suggesting that either season itself or some factor correlated with season, such as food availability, caused the change. Water saving has been proposed as a selective advantage of heterothermy in other large mammals, but in kangaroos the water savings would have been small and not required in a reserve with permanent standing water. We calculate that the lower core temperature could provide energy savings of nearly 7%. It is likely that the heterothermy that we observed on hot days results either from decreased energy intake during the dry season or from a seasonal pattern entrained in the kangaroos that presumably has been selected for because of decreased energy availability during the dry season.

  15. Time in Bed is Associated with Decreased Physical Activity and Higher BMI in Women Seeking Weight Loss Treatment.

    PubMed

    Hart, Chantelle N; Fava, Joseph L; Subak, Leslee L; Stone, Katie; Vittinghoff, Eric; Demos, Kathryn; O'Brien, Erin; Cairns, Alyssa; Wing, Rena

    2012-01-01

    Short sleep duration is associated with obesity risk. Despite calls to incorporate strategies to enhance sleep within the context of behavioral weight loss (BWL) treatment, little is known regarding the association between sleep and body mass index (BMI) among individuals presenting for BWL. Moreover, most research has focused on eating pathways linking sleep and BMI, and have not explored how sleep may impact engagement in physical activity. The purpose of the present study was to determine whether, in a sample of women seeking treatment for weight loss, there was an association between reported time in bed (TIB), higher BMI, lower physical activity, and less favorable dietary composition. Prior to randomization, 318 women completed measures of TIB, eating, and activity; weight and height were measured. Findings demonstrated that report of '6 hours or less' TIB/night was associated with higher BMI and lower reported physical activity compared to the referent (>7 to ≤ 8 hours/night). It was not associated with the number of reported calories consumed each day or with the percent of calories consumed from fat, carbohydrates or protein. Better understanding the role of sleep within the context of BWL treatment in women seems warranted.

  16. Decreased activity of the 20S proteasome in the brain white matter and gray matter of patients with multiple sclerosis.

    PubMed

    Zheng, Jianzheng; Bizzozero, Oscar A

    2011-04-01

    Carbonylated (oxidized) proteins are known to accumulate in the cerebral white matter (WM) and gray matter (GM) of patients with multiple sclerosis (MS). Although oxidative stress is necessary for carbonyl generation, it is the failure of the degradation systems that ultimately leads to the build-up of carbonylated proteins within tissues. In this study, we measured the activity of the 20S proteasome and other proteolytic systems in the cerebral WM and GM of 13 MS patients and 13 controls. We report that the activities of the three peptidases of the 20S proteasome (i.e. chymotrypsin-like, caspase-like and trypsin-like) in both MS-WM and MS-GM are greatly reduced. Interestingly, neither the amount of proteasome nor the levels of the catalytic subunits (β1, β2, and β5) are diminished in this disease. Proteins containing Lys-48 poly-ubiquitin also accumulate in MS tissues, indicating failure of the 26S proteasome as well. Levels of the regulatory caps 11S α and 19S are also lower in MS than in controls, suggesting that the activity of the more complex proteasomes may be reduced further. Finally, the activities of other proteases that might also remove oxidized proteins (calpain, cathepsin B, mitochondrial LonP) are not lessened in MS. Together, these studies suggest that direct inactivation of proteolytic centers in the 20S particle and/or the presence of specific inhibitors is the underlying cause of proteasomal dysfunction in MS.

  17. Prenatal malnutrition leads to deficits in attentional set shifting and decreases metabolic activity in prefrontal subregions that control executive function.

    PubMed

    McGaughy, Jill A; Amaral, Ana C; Rushmore, R Jarrett; Mokler, David J; Morgane, Peter J; Rosene, Douglas L; Galler, Janina R

    2014-01-01

    Globally, over 25% of all children under the age of 5 years experience malnutrition leading to cognitive and emotional impairments that can persist into adulthood and beyond. We use a rodent model to determine the impact of prenatal protein malnutrition on executive functions in an attentional set-shifting task and metabolic activity in prefrontal cortex (PFC) subregions critical to these behaviors. Long-Evans dams were provided with a low (6% casein) or adequate (25% casein) protein diet 5 weeks before mating and during pregnancy. At birth, the litters were culled to 8 pups and fostered to control dams on the 25% casein diet. At postnatal day 90, prenatally malnourished rats were less able to shift attentional set and reverse reward contingencies than controls, demonstrating cognitive rigidity. Naive same-sexed littermates were assessed for regional brain activity using the metabolic marker (14)C-2-deoxyglucose (2DG). The prenatally malnourished rats had lower metabolic activity than controls in prelimbic, infralimbic, anterior cingulate, and orbitofrontal cortices, but had comparable activity in the nearby piriform cortex and superior colliculus. This study demonstrates that prenatal protein malnutrition in a well-described animal model produces cognitive deficits in tests of attentional set shifting and reversal learning, similar to findings of cognitive inflexibility reported in humans exposed to early childhood malnutrition. PMID:25342495

  18. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    SciTech Connect

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  19. Decreased peroxisome proliferator-activated receptor γ level and signalling in sebaceous glands of patients with acne vulgaris.

    PubMed

    Dozsa, A; Mihaly, J; Dezso, B; Csizmadia, E; Keresztessy, T; Marko, L; Rühl, R; Remenyik, E; Nagy, L

    2016-07-01

    Little is known about the altered lipid metabolism-related transcriptional events occuring in sebaceous glands of patients with acne vulgaris. Peroxisome proliferator-activated receptor (PPAR)γ, a lipid-activated transcription factor, is implicated in differentiation and lipid metabolism of sebocytes. We have observed that PPARγ and its target genes, ADRP (adipose differentiation related protein) and PGAR (PPARγ angioprotein related protein) are expressed at lower levels in sebocytes from patients with acne than in those from healthy controls (HCs) Furthermore, endogenous PPARγ activator lipids such as arachidonic acid-derived keto-metabolites (e.g. 5KETE, 12KETE) are increased in acne-involved and nonacne-involved skin of patients with acne, compared with skin from healthy individuals. Our findings highlight the possible anti-inflammatory role of endogenous ligand-activated PPARγ signaling in human sebocyte biology, and suggest that modulating PPARγ- expression and thereby signaling might be a promising strategy for the clinical management of acne vulgaris.

  20. Decreased glutathione S-transferase expression and activity and altered sex steroids in Lake Apopka brown bullheads (Ameriurus nebulosus)

    USGS Publications Warehouse

    Gallagher, E.P.; Gross, T.S.; Sheehy, K.M.

    2001-01-01

    A number of freshwater lakes and reclaimed agricultural sites in Central Florida have been the receiving waters for agrochemical and municipal runoff. One of these sites, Lake Apopka, is also a eutrophic system that has been the focus of several case studies reporting altered reproductive activity linked to bioaccumulation of persistent organochlorine chemicals in aquatic species. The present study was initiated to determine if brown bullheads (Ameriurus nebulosus) from the north marsh of Lake Apopka (Lake Apopka Marsh) exhibit an altered capacity to detoxify environmental chemicals through hepatic glutathione S-transferase (GST)-mediated conjugation as compared with bullheads from a nearby reference site (Lake Woodruff). We also compared plasma sex hormone concentrations (testosterone, 17-?? estradiol, and 11 keto-testosterone) in bullheads from the two sites. Female bullheads from Lake Apopka had 40% lower initial rate GST conjugative activity toward 1-chloro-2,4-dinitrobenzene (CDNB), 50% lower activity towards p-nitrobutyl chloride (NBC), 33% lower activity toward ethacrynic acid (ECA), and 43% lower activity toward ??5-androstene-3,17-dione (??5-ADI), as compared with female bullheads from Lake Woodruff. Enzyme kinetic analyses demonstrated that female bullheads from Lake Apopka had lower GST-catalyzed CDNB clearance than did female Lake Woodruff bullheads. Western blotting studies of bullhead liver cytosolic proteins demonstrated that the reduced GST catalytic activities in female Lake Apopka bullheads were accompanied by lower expression of hepatic GST protein. No site differences were observed with respect to GST activities or GST protein expression in male bullheads. Female Lake Apopka bullheads also had elevated concentrations of plasma androgens (testosterone and 11-ketotestosterone) as compared with females from Lake Woodruff. In contrast, male Lake Apopka bullheads had elevated levels of plasma estrogen but similar levels of androgens as compared with

  1. Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

    PubMed Central

    2010-01-01

    Background Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. Methods We studied nineteen neonates (27.3 ± 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO2 and VCO2 measured by gas chromatography. Results REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO2 (7.4 ± 1.9 vs 10 ± 1.5 ml/kg/min) and VCO2 (5.1 ± 1.7 vs 7.4 ± 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01). Conclusion REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities. PMID:20653967

  2. When Genomics Is Not Enough: Experimental Evidence for a Decrease in LINE-1 Activity During the Evolution of Australian Marsupials.

    PubMed

    Gallus, Susanne; Lammers, Fritjof; Nilsson, Maria Anna

    2016-01-01

    The autonomous transposable element LINE-1 is a highly abundant element that makes up between 15% and 20% of therian mammal genomes. Since their origin before the divergence of marsupials and placental mammals, LINE-1 elements have contributed actively to the genome landscape. A previous in silico screen of the Tasmanian devil genome revealed a lack of functional coding LINE-1 sequences. In this study we present the results of an in vitro analysis from a partial LINE-1 reverse transcriptase coding sequence in five marsupial species. Our experimental screen supports the in silico findings of the genome-wide degradation of LINE-1 sequences in the Tasmanian devil, and identifies a high frequency of degraded LINE-1 sequences in other Australian marsupials. The comparison between the experimentally obtained LINE-1 sequences and reference genome assemblies suggests that conclusions from in silico analyses of retrotransposition activity can be influenced by incomplete genome assemblies from short reads. PMID:27389686

  3. When Genomics Is Not Enough: Experimental Evidence for a Decrease in LINE-1 Activity During the Evolution of Australian Marsupials

    PubMed Central

    Gallus, Susanne; Lammers, Fritjof

    2016-01-01

    The autonomous transposable element LINE-1 is a highly abundant element that makes up between 15% and 20% of therian mammal genomes. Since their origin before the divergence of marsupials and placental mammals, LINE-1 elements have contributed actively to the genome landscape. A previous in silico screen of the Tasmanian devil genome revealed a lack of functional coding LINE-1 sequences. In this study we present the results of an in vitro analysis from a partial LINE-1 reverse transcriptase coding sequence in five marsupial species. Our experimental screen supports the in silico findings of the genome-wide degradation of LINE-1 sequences in the Tasmanian devil, and identifies a high frequency of degraded LINE-1 sequences in other Australian marsupials. The comparison between the experimentally obtained LINE-1 sequences and reference genome assemblies suggests that conclusions from in silico analyses of retrotransposition activity can be influenced by incomplete genome assemblies from short reads. PMID:27389686

  4. Extrusion decreases the negative effects of kidney bean on enzyme and transport activities of the rat small intestine.

    PubMed

    Marzo, F; Milagro, F I; Urdaneta, E; Barrenetxe, J; Ibañez, F C

    2011-10-01

    The objective of the present study was to evaluate the influence of raw and extruded kidney bean (Phaseolus vulgaris L. var. Pinto) consumption on the gut physiology of young growing rats. The intestinal enzyme activity (sucrase, maltase, Na(+) /K(+) ATPase, aminopeptidase N, dipeptidylpeptidase IV, alkaline phosphatase) and the uptake of sugar (d-galactose) and amino acids (l-leucine) were measured in brush border membrane vesicles. Five groups of growing male Wistar rats were fed ad libitum for 15 days on five different 10% protein diets: one containing casein as the main source of protein (Control, C), and four containing raw (RKB1, RKB6) or extruded kidney bean (EKB1, EKB6) at 1% and 6% of total protein content respectively. Extrusion treatment significantly reduced the content of bioactive factors (phytates, tannins) and abolished lectins, trypsin, chymotrypsin, and α-amylase inhibitory activities. Rats fed raw beans (especially RKB6) showed lower growth rate and food intake as compared to those fed extruded legumes, probably due to the high levels of lectins and other anti-nutritive factors in the raw beans. Gut enzymatic activities and uptake of d-galactose and l-leucine were lower in RKB6 and RKB1-fed animals, although they significantly improved in the groups fed extruded beans. Enzymatic activity and uptake in EKB1 were similar to those of casein-fed rats, whereas the uptake and growth rate of EKB6 were different to the control. This is attributable to the higher non-thermolabile biofactor content in the EKB6 diet, especially phytates and tannins, than in EKB1. This article shows the dose-dependent toxicological effects of bioactive factors contained in kidney beans on gut function. The extrusion process reduced their adverse impact on gut physiology and growth rate.

  5. Extrusion decreases the negative effects of kidney bean on enzyme and transport activities of the rat small intestine.

    PubMed

    Marzo, F; Milagro, F I; Urdaneta, E; Barrenetxe, J; Ibañez, F C

    2011-10-01

    The objective of the present study was to evaluate the influence of raw and extruded kidney bean (Phaseolus vulgaris L. var. Pinto) consumption on the gut physiology of young growing rats. The intestinal enzyme activity (sucrase, maltase, Na(+) /K(+) ATPase, aminopeptidase N, dipeptidylpeptidase IV, alkaline phosphatase) and the uptake of sugar (d-galactose) and amino acids (l-leucine) were measured in brush border membrane vesicles. Five groups of growing male Wistar rats were fed ad libitum for 15 days on five different 10% protein diets: one containing casein as the main source of protein (Control, C), and four containing raw (RKB1, RKB6) or extruded kidney bean (EKB1, EKB6) at 1% and 6% of total protein content respectively. Extrusion treatment significantly reduced the content of bioactive factors (phytates, tannins) and abolished lectins, trypsin, chymotrypsin, and α-amylase inhibitory activities. Rats fed raw beans (especially RKB6) showed lower growth rate and food intake as compared to those fed extruded legumes, probably due to the high levels of lectins and other anti-nutritive factors in the raw beans. Gut enzymatic activities and uptake of d-galactose and l-leucine were lower in RKB6 and RKB1-fed animals, although they significantly improved in the groups fed extruded beans. Enzymatic activity and uptake in EKB1 were similar to those of casein-fed rats, whereas the uptake and growth rate of EKB6 were different to the control. This is attributable to the higher non-thermolabile biofactor content in the EKB6 diet, especially phytates and tannins, than in EKB1. This article shows the dose-dependent toxicological effects of bioactive factors contained in kidney beans on gut function. The extrusion process reduced their adverse impact on gut physiology and growth rate. PMID:21114542

  6. Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1994-01-01

    The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

  7. Benevolent sexist ideology attributed to an abusive partner decreases women's active coping responses to acts of sexual violence.

    PubMed

    Durán, Mercedes; Moya, Miguel; Megías, Jesús L

    2014-05-01

    This article describes three studies in which we explored the influence of the sexist ideology attributed to the perpetrator on women's responses to hypothetical acts of sexual assault perpetrated by male intimate partners. In Study 1 (n = 83), college women read three sexual assault scenarios in the context of an intimate relationship. The male partner's sexist ideology (benevolent, hostile, or control) was manipulated within participants. Women showed less active responses when the partner had been described as a benevolent sexist man. This effect was replicated in Study 2 (n = 103), which showed a relationship between women's less active responses and the belief that benevolent sexist men are very attracted to and interested in their partners. Study 3 (n = 130) demonstrated experimentally that women's responses are less active when they are exposed to information that indicates that the perpetrator is both high in benevolent sexism and highly attracted to his victim than when the latter information is not provided. Results suggest that sexist ideology and particularly benevolent sexism-attributed to the perpetrator in this case-is highly important in women's reactions to acts of sexual violence perpetrated by male intimate partners.

  8. Syzygium cumini extract decrease adenosine deaminase, 5'nucleotidase activities and oxidative damage in platelets of diabetic patients.

    PubMed

    De Bona, Karine S; Bellé, Luziane P; Sari, Marcel H; Thomé, Gustavo; Schetinger, Maria R C; Morsch, Vera M; Boligon, Aline; Athayde, Margareth L; Pigatto, Aline S; Moretto, Maria B

    2010-01-01

    Diabetes mellitus, a chronic metabolic disorder, has assumed epidemic proportions and its long-term complications can have devastating consequences. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Syzygium cumini is being widely used to treat diabetes by the traditional practitioners over many centuries. Adenosine deaminase (ADA) and 5'-Nucleotidase (5'NT) are enzymes of purine nucleoside metabolism that play an important role in the regulation of adenosine (Ado) levels. In this study, we investigated the effect of Syzygium cumini aqueous leaves extract (ASc) on ADA and 5'NT activities and on parameters of oxidative stress under in vitro conditions, using platelets of patients with Type 2 diabetes mellitus. Platelet-Rich Plasma (PRP) was assayed by ADA, 5'NT, Catalase (CAT), Superoxide Dismutase (SOD) activities and Thiobarbituric acid reactive substances (TBARS) levels. We observed that ADA, 5'NT activities and TBARS levels were significantly higher when compared to the control group, and ASc (100 and 200 μg/mL) prevented these effects. Our study demonstrates that ASc was able to remove oxidant species generated in diabetic conditions and modulates in the Ado levels. Then, ASc may promote a compensatory response in platelet function, improving the susceptibility-induced by the diabetes mellitus. PMID:21063110

  9. Activation energies to characterize ease of removal of various kinds of oxygen from bismuth molybdate

    SciTech Connect

    Dadyburjor, D.B.; Ruckenstein, E.

    1980-06-01

    Calculations by the method of minimum energy paths showed that oxygen(-2) anions are more easily displaced from molybdenum(VI) or from the layer between molybdenum and bismuth than from bismuth(III) of a 2:1 bismuth molybdate (Bi/sub 2/MoO/sub 6/). However, available experimental evidence suggests that the oxygen of the bismuth layer is active in the selective oxidation of hydrocarbons; apparently the presence of the hydrocarbon decreases the energy barrier required for transfer of the oxygen anion, and anion vacancies generated, e.g., in a prereduction of the catalyst, also decrease the energy barrier.

  10. Heparin (GAG-hed) inhibits LCR activity of Human Papillomavirus type 18 by decreasing AP1 binding

    PubMed Central

    Villanueva, Rita; Morales-Peza, Néstor; Castelán-Sánchez, Irma; García-Villa, Enrique; Tapia, Rocio; Cid-Arregui, Ángel; García-Carrancá, Alejandro; López-Bayghen, Esther; Gariglio, Patricio

    2006-01-01

    Background High risk HPVs are causative agents of anogenital cancers. Viral E6 and E7 genes are continuously expressed and are largely responsible for the oncogenic activity of these viruses. Transcription of the E6 and E7 genes is controlled by the viral Long Control Region (LCR), plus several cellular transcription factors including AP1 and the viral protein E2. Within the LCR, the binding and activity of the transcription factor AP1 represents a key regulatory event in maintaining E6/E7 gene expression and uncontrolled cell proliferation. Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have also shown antiviral effects and inhibition of AP1 transcriptional activity. The purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral and antitumoral agent in an HPV18 positive HeLa cell line. Methods Using in vivo and in vitro approaches we tested GAG-hed effects on HeLa tumour cell growth, cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA. Results We were able to record the antitumoral effect of GAG-hed in vivo by using as a model tumours induced by injection of HeLa cells into athymic female mice. The antiviral effect of GAG-hed resulted in the inhibition of LCR activity and, consequently, the inhibition of E6 and E7 transcription. A specific diminishing of cell proliferation rates was observed in HeLa but not in HPV-free colorectal adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the percentage of cells in G2/M phase of the cell cycle was increased. We also detected that GAG-hed prevents the binding of the transcription factor AP1 to the LCR. Conclusion Direct interaction of GAG-hed with the components of the AP1 complex and subsequent interference with its ability to correctly bind specific sites within the viral LCR may contribute to the inhibition of E6/E7 transcription and cell proliferation. Our data

  11. Motor overflow in children with attention-deficit/hyperactivity disorder is associated with decreased extent of neural activation in the motor cortex.

    PubMed

    Gaddis, Andrew; Rosch, Keri S; Dirlikov, Benjamin; Crocetti, Deana; MacNeil, Lindsey; Barber, Anita D; Muschelli, John; Caffo, Brian; Pekar, James J; Mostofsky, Stewart H

    2015-09-30

    Motor overflow is a developmental phenomenon that typically disappears by late childhood. Abnormal persistence of motor overflow is often present in children with attention-deficit/hyperactivity disorder (ADHD). This study employed functional magnetic resonance imaging (fMRI) during a finger-sequencing task to examine whether excessive motor overflow in children with ADHD is associated with decreased extent of motor circuit activation. Thirty-four right-handed children (18 typically developing controls, 16 ADHD) completed fMRI while performing a finger-sequencing task. Motor overflow was evaluated during a finger-sequencing task and a motor examination (the PANESS) performed outside the scanner. Diagnostic differences in behavioral measures of overflow and extent of activation in the contralateral and ipsilateral motor network ROIs were examined, along with correlations between overflow and extent of activation. Children with ADHD demonstrated greater overflow and lesser extent of activation in left primary motor cortex (BA4) and bilateral premotor cortex (BA6) and supplementary motor area (SMA) during right-hand finger-sequencing compared to controls. Decreased extent of primary motor and premotor activation correlated with increased hand-related overflow movements in children with ADHD but not controls. These findings suggest that overflow movements in children with ADHD may reflect decreased recruitment of neural circuitry involved in active inhibition of homologous motor circuitry unnecessary to task execution.

  12. Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation.

    PubMed

    Tomasino, Barbara; Fabbro, Franco

    2016-02-01

    Mindfulness meditation is a form of attention control training. The training exercises the ability to repeatedly focus attention. We addressed the activation changes related to an 8-weeks mindfulness-oriented focused attention meditation training on an initially naïve subject cohort. Before and after training participants underwent an fMRI experiment, thus, although not strictly a cross over design, they served as their internal own control. During fMRI they exercised focused attention on breathing and body scan as compared to resting. We found increased and decreased activation in different parts of the prefrontal cortex (PFC) by comparing pre- vs. post-mindfulness training (MT) during breathing and body scan meditation exercises that were compared against their own resting state. In the post-MT (vs. pre-MT) meditation increased activation in the right dorsolateral PFC and in the left caudate/anterior insula and decreased activation in the rostral PFC and right parietal area 3b. Thus a brief mindfulness training caused increased activation in areas involved in sustaining and monitoring the focus of attention (dorsolateral PFC), consistent with the aim of mindfulness that is exercising focused attention mechanisms, and in the left caudate/anterior insula involved in attention and corporeal awareness and decreased activation in areas part of the "default mode" network and is involved in mentalizing (rostral PFC), consistent with the ability trained by mindfulness of reducing spontaneous mind wandering. PMID:26720411

  13. Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation.

    PubMed

    Tomasino, Barbara; Fabbro, Franco

    2016-02-01

    Mindfulness meditation is a form of attention control training. The training exercises the ability to repeatedly focus attention. We addressed the activation changes related to an 8-weeks mindfulness-oriented focused attention meditation training on an initially naïve subject cohort. Before and after training participants underwent an fMRI experiment, thus, although not strictly a cross over design, they served as their internal own control. During fMRI they exercised focused attention on breathing and body scan as compared to resting. We found increased and decreased activation in different parts of the prefrontal cortex (PFC) by comparing pre- vs. post-mindfulness training (MT) during breathing and body scan meditation exercises that were compared against their own resting state. In the post-MT (vs. pre-MT) meditation increased activation in the right dorsolateral PFC and in the left caudate/anterior insula and decreased activation in the rostral PFC and right parietal area 3b. Thus a brief mindfulness training caused increased activation in areas involved in sustaining and monitoring the focus of attention (dorsolateral PFC), consistent with the aim of mindfulness that is exercising focused attention mechanisms, and in the left caudate/anterior insula involved in attention and corporeal awareness and decreased activation in areas part of the "default mode" network and is involved in mentalizing (rostral PFC), consistent with the ability trained by mindfulness of reducing spontaneous mind wandering.

  14. Inactivation of thioredoxin f1 leads to decreased light activation of ADP-glucose pyrophosphorylase and altered diurnal starch turnover in leaves of Arabidopsis plants.

    PubMed

    Thormählen, Ina; Ruber, Joachim; von Roepenack-Lahaye, Edda; Ehrlich, Sven-Matthias; Massot, Vincent; Hümmer, Christine; Tezycka, Justyna; Issakidis-Bourguet, Emmanuelle; Geigenberger, Peter

    2013-01-01

    Chloroplast thioredoxin f (Trx f) is an important regulator of primary metabolic enzymes. However, genetic evidence for its physiological importance is largely lacking. To test the functional significance of Trx f in vivo, Arabidopsis mutants with insertions in the trx f1 gene were studied, showing a drastic decrease in Trx f leaf content. Knockout of Trx f1 led to strong attenuation in reductive light activation of ADP-glucose pyrophosphorylase (AGPase), the key enzyme of starch synthesis, in leaves during the day and in isolated chloroplasts, while sucrose-dependent redox activation of AGPase in darkened leaves was not affected. The decrease in light-activation of AGPase in leaves was accompanied by a decrease in starch accumulation, an increase in sucrose levels and a decrease in starch-to-sucrose ratio. Analysis of metabolite levels at the end of day shows that inhibition of starch synthesis was unlikely due to shortage of substrates or changes in allosteric effectors. Metabolite profiling by gas chromatography-mass spectrometry pinpoints only a small number of metabolites affected, including sugars, organic acids and ethanolamine. Interestingly, metabolite data indicate carbon shortage in trx f1 mutant leaves at the end of night. Overall, results provide in planta evidence for the role played by Trx f in the light activation of AGPase and photosynthetic carbon partitioning in plants.

  15. Dietary fish oil replacement with palm or poultry oil increases fillet oxidative stability and decreases liver glutathione peroxidase activity in barramundi (Lates calcarifer).

    PubMed

    Wan Ahmad, Wan A R; Stone, David A J; Schuller, Kathryn A

    2013-12-01

    Complete dietary fish oil replacement with palm or poultry oil in barramundi (Lates calcarifer) had no detrimental effects on growth or hepatosomatic index of juvenile fish up to an average size of ~50 g. However, it significantly decreased the omega-3 (n-3) long-chain polyunsaturated fatty acid content of the fish muscle (fillet) lipids. This was particularly true for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which are recognised for their health beneficial effects in the human diet. As a result of their decreased EPA and DHA content, the peroxidation index of the muscle lipids was also decreased. This was associated with increased simulated retail storage shelf life as indicated by decreased thiobarbituric acid reactive substances in muscle samples from fish fed the palm or poultry oil-based diets. Concomitantly, glutathione peroxidase (GPx) activity, but not glutathione S-transferase (GST) activity or reduced glutathione concentration, was significantly reduced in the liver of barramundi fed the palm or poultry oil-based diets as compared with the fish fed the fish oil-based diet. Furthermore, GPx and GST activity were very low in muscle, much lower than in gastrointestinal tract, liver or swim bladder. Therefore, we propose that liver GPx activity may be a good predictor of fillet shelf life in barramundi and other fish species.

  16. Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

    PubMed

    Batistela, Emanuele; Pereira, Mayara Peron; Siqueira, Juliany Torres; Paula-Gomes, Silvia; Zanon, Neusa Maria; Oliveira, Eduardo Brandt; Navegantes, Luiz Carlos Carvalho; Kettelhut, Isis C; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda; Baviera, Amanda Martins

    2014-06-01

    The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

  17. Decreased physical activity and cardiorespiratory fitness in adults with ankylosing spondylitis: a cross-sectional controlled study.

    PubMed

    O'Dwyer, Tom; O'Shea, Finbar; Wilson, Fiona

    2015-11-01

    The health benefits of physical activity (PA) in the general population are numerous; however, few studies have measured PA among adults with ankylosing spondylitis (AS). The aims of this study were to: (1) objectively measure the PA levels and cardiorespiratory fitness of adults with AS and compare these to population controls, and (2) examine the relationships between PA, cardiorespiratory function and condition-specific outcomes. This cross-sectional study included participants (>18 years) meeting the modified New York criteria for AS, and matched population controls. Exclusion criteria were the presence of comorbidities limiting PA, or recent changes in medication usage. Participants completed clinical questionnaires assessing disease activity, physical function and quality of life. Tri-axial accelerometers recorded habitual PA over 1 week. Cardiorespiratory fitness was assessed by submaximal treadmill test with breath-by-breath gas analysis and heart rate monitoring. Thirty-nine adults with AS and 39 controls were recruited. The AS group spent significantly less time performing vigorous-intensity PA than controls [mean difference (95 % CI) 1.8 min/day (1.2-2.7)] and performed significantly fewer bouts of health-enhancing PA [1.7 min/day (1.1-2.5)]. The AS group had significantly lower predicted VO(2MAX) than controls [6.0 mL kg(-1) min(-1) (1.8-10.1)]. PA was associated with aerobic capacity. Sedentary time was associated with disease activity and physical function. Adults with AS participate in less health-enhancing PA than population controls. Fewer than half meet PA recommendations, despite exercise being a key component of AS management. Explorations of PA behaviour and strategies to increase PA participation are needed.

  18. Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty?

    PubMed Central

    Merz, Christian J.; Dresler, Thomas; Heupel, Julia; Reichert, Susanne; Jacob, Christian P.; Deckert, Jürgen; Herrmann, Martin J.

    2016-01-01

    Background: Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Methods: Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. Results: There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Conclusions: Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. PMID:27207920

  19. Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

    PubMed Central

    Zeidán-Chuliá, Fares; Kolling, Eduardo Antônio; Rybarczyk-Filho, José Luiz; Ambrosi, Priscilla; Resende Terra, Silvia; Pires, André Simões; da Rocha, João Batista Teixeira; Antônio Behr, Guilherme; Fonseca Moreira, José Cláudio

    2013-01-01

    Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL), taurine (1–16 mg/mL), and guarana (3.125–50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”), could be a cause of in vitro toxicity induced by these drugs. PMID:23766861

  20. Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor

    PubMed Central

    Kuban-Jankowska, Alicja; Sahu, Kamlesh K.; Gorska, Magdalena; Tuszynski, Jack A.; Wozniak, Michal

    2016-01-01

    Chicoric acid (CA) is a phenolic compound present in dietary supplements with a large spectrum of biological properties reported ranging from antioxidant, to antiviral, to immunostimulatory properties. Due to the fact that chicoric acid promotes phagocytic activity and was reported as an allosteric inhibitor of the PTP1B phosphatase, we examined the effect of CA on YopH phosphatase from pathogenic bacteria, which block phagocytic processes of a host cell. We performed computational studies of chicoric acid binding to YopH as well as validation experiments with recombinant enzymes. In addition, we performed similar studies for caffeic and chlorogenic acids to compare the results. Docking experiments demonstrated that, from the tested compounds, only CA binds to both catalytic and secondary binding sites of YopH. Our experimental results showed that CA reduces activity of recombinant YopH phosphatase from Yersinia enterocolitica and human CD45 phosphatase. The inhibition caused by CA was irreversible and did not induce oxidation of catalytic cysteine. We proposed that inactivation of YopH induced by CA is involved with allosteric inhibition by interacting with essential regions responsible for ligand binding. PMID:26735581

  1. Sample Energy Conservation Education Activities for Elementary School Students.

    ERIC Educational Resources Information Center

    Allen, Rodney F., Ed.; LaHart, David E., Ed.

    The booklet contains learning activities for introducing energy and conservation concepts into the existing elementary school curriculum. The activities were developed by Palm Beach County teachers during a one-week workshop. A framework of ideas is divided into three functional categories: universe of energy, living systems and energy, and social…

  2. Knockout of inositol-requiring enzyme 1α in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure

    PubMed Central

    Xiao, Yuzhong; Xia, Tingting; Yu, Junjie; Deng, Yalan; Liu, Hao; Liu, Bin; Chen, Shanghai; Liu, Yong

    2016-01-01

    Although numerous functions of inositol-requiring enzyme 1α (IRE1α) have been identified, a role of IRE1α in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus is largely unknown. Here, we showed that mice lacking IRE1α specifically in POMC neurons (PIKO) are lean and resistant to high-fat diet-induced obesity and obesity-related insulin resistance, liver steatosis and leptin resistance. Furthermore, PIKO mice had higher energy expenditure, probably due to increased thermogenesis in brown adipose tissue. Additionally, α-melanocyte-stimulating hormone production was increased in the hypothalamus of PIKO mice. These results demonstrate that IRE1α in POMC neurons plays a critical role in the regulation of obesity and obesity-related metabolic disorders. Our results also suggest that IRE1α is not only an endoplasmic reticulum stress sensor, but also a new potential therapeutic target for obesity and obesity-related metabolic diseases. PMID:27558934

  3. Knockout of inositol-requiring enzyme 1α in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure.

    PubMed

    Xiao, Yuzhong; Xia, Tingting; Yu, Junjie; Deng, Yalan; Liu, Hao; Liu, Bin; Chen, Shanghai; Liu, Yong; Guo, Feifan

    2016-08-01

    Although numerous functions of inositol-requiring enzyme 1α (IRE1α) have been identified, a role of IRE1α in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus is largely unknown. Here, we showed that mice lacking IRE1α specifically in POMC neurons (PIKO) are lean and resistant to high-fat diet-induced obesity and obesity-related insulin resistance, liver steatosis and leptin resistance. Furthermore, PIKO mice had higher energy expenditure, probably due to increased thermogenesis in brown adipose tissue. Additionally, α-melanocyte-stimulating hormone production was increased in the hypothalamus of PIKO mice. These results demonstrate that IRE1α in POMC neurons plays a critical role in the regulation of obesity and obesity-related metabolic disorders. Our results also suggest that IRE1α is not only an endoplasmic reticulum stress sensor, but also a new potential therapeutic target for obesity and obesity-related metabolic diseases. PMID:27558934

  4. Decreased spontaneous activity in AMPK α2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism.

    PubMed

    Møller, Lisbeth L V; Sylow, Lykke; Gøtzsche, Casper R; Serup, Annette K; Christiansen, Søren H; Weikop, Pia; Kiens, Bente; Woldbye, David P D; Richter, Erik A

    2016-10-01

    It is well known that physical activity has several health benefits, yet many people do not exercise. Dopamine levels in the striatum of the brain are thought to be important for the motivation to exercise. Conversely, we hypothesized that muscle quality can affect the motivation to exercise through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared to WT when treated with saline or cocaine, respectively, but the increase induced by cocaine was similar in AMPK α2 KD and WT mice. The efflux of dopamine in ventral striatum after cocaine treatment increased similarly by 2.5-fold in the two genotypes, and basal levels of dopamine and its metabolites DOPAC and HVA were also similar between genotypes. These findings show that decreased AMPK activity in muscle leads to decreased voluntary activity which is not due to secondary abnormalities in dopamine levels in the ventral striatum or sensitivity to cocaine. Thus, decreased voluntary activity in AMPK muscle deficient mice is most likely unrelated to regulation of brain dopamine content and metabolism. PMID:27306083

  5. Activation of histamine H3 receptor decreased cytoplasmic Ca(2+) imaging during electrical stimulation in the skeletal myotubes.

    PubMed

    Chen, Yan; Paavola, Jere; Stegajev, Vasili; Stark, Holger; Chazot, Paul L; Wen, Jian Guo; Konttinen, Yrjö T

    2015-05-01

    Histamine is a neurotransmitter and chemical mediator in multiple physiological processes. Histamine H3 receptor is expressed in the nervous system, heart, and gastrointestinal tract; however, little is known about H3 receptor in skeletal muscle. The aim of this study was to investigate the role of H3 receptor in skeletal myotubes. The expression of H3 receptor and myosin heavy chain (MHC), a late myogenesis marker, was assessed by real-time PCR and immunostaining in C2C12 skeletal myogenesis and adult mid-urethral skeletal muscle tissues. H3 receptor mRNA showed a significant increase upon differentiation of C2C12 into myotubes: 1-, 26-, 91-, and 182-fold at days 0, 2, 4, and 6, respectively. H3 receptor immunostaining in differentiated C2C12 cells and adult skeletal muscles was positive and correlated with that of MHC. The functional role of H3receptor in differentiated myotubes was assessed using an H3 receptor agonist, (R)-a-methylhistamine ((R)-α-MeHA). Ca(2+) imaging, stimulated by electric pacing, was decreased by 55% after the treatment of mature C2C12 myotubes with 1μM (R)-α-MeHA for 10min and 20min, while treatment with 100nm (R)-α-MeHA for 5min caused 45% inhibition. These results suggested that H3 receptor may participate in the maintenance of the relaxed state and prevention of over-contraction in mature differentiated myotubes. The elucidation of the role of H3R in skeletal myogenesis and adult skeletal muscle may open a new direction in the treatment of skeletal muscle disorders, such as muscle weakness, atrophy, and myotonia in motion systems or peri-urethral skeletal muscle tissues.

  6. Decreasing the damage in smart structures using integrated online DDA/ISMP and semi-active control

    NASA Astrophysics Data System (ADS)

    Karami, K.; Amini, F.

    2012-10-01

    Integrated structural health monitoring (SHM) and vibration control has been considered recently by researchers. Up to now, all of the research in the field of integrated SHM and vibration control has been conducted using control devices and control algorithms to enhance system identification and damage detection. In this study, online SHM is used to improve the performance of structural vibration control, unlike previous research. Also, a proposed algorithm including integrated online SHM and a semi-active control strategy is used to reduce both damage and seismic response of the main structure due to strong seismic disturbance. In the proposed algorithm the nonlinear behavior of the building structure is simulated during the excitation. Then, using the measured data and the damage detection algorithm based on identified system Markov parameters (DDA/ISMP), a method proposed by the authors, damage corresponding to axial and bending stiffness of all structural elements is identified. In this study, a 20 t MR damper is employed as a control device to mitigate both damage and dynamic response of the building structure. Also, the interaction between SHM and a semi-active control strategy is assessed. To illustrate the efficiency of the proposed algorithm, a two bay two story steel braced frame structure is used. By defining the damage index and damage rate index, the input current of the MR damper is generated using a fuzzy logic controller. The obtained results show that the possibility of smart building creation is provided using the proposed algorithm. In comparison to the widely used strategy of only vibration control, it is shown that the proposed algorithm is more effective. Furthermore, in the proposed algorithm, the total consumed current intensity and generated control forces are considerably less than for the strategy of only vibration control.

  7. The decrease in body fat in mice fed conjugated linoleic acid is due to increases in energy expenditure and energy loss in the excreta.

    PubMed

    Terpstra, A H M; Beynen, A C; Everts, H; Kocsis, S; Katan, M B; Zock, P L

    2002-05-01

    We carried out energy balance studies in four groups of young, growing, 5-wk-old Balb-C mice (n = 12/group) that were either food restricted or nonrestricted and fed high fat diets (38 energy%) with or without 0.93 g/100 g conjugated linoleic acid (CLA) for 39 d. The energy in carcasses, excreta and food was measured in a bomb calorimeter. CLA lowered the percentage of the energy intake that was stored in the body from 1.9 +/- 0.8 to -2.3 +/- 0.7% (mean +/- SD, P < 0.05) in the nonrestricted mice and from 1.4 +/- 1.3 to -2.9 +/- 0.7% (P < 0.05) in the restricted mice. Thus, the CLA-treated mice had a net loss of body energy. The percentage of the energy intake eliminated in the excreta increased from 7.6 +/- 0.9% in controls to 8.7 +/- 1.0% (P < 0.05) in the CLA-treated mice that were nonrestricted and from 7.3 +/- 0.8 to 8.4 +/- 0.6 (P < 0.05) in the restricted mice. The amount of energy ingested minus the amount retained in carcasses and excreta equals the energy expenditure. The percentage of the energy intake that was expended as heat increased from 90.5 +/- 1.2 in controls to 93.6 +/- 1.5% (P < 0.05) in the CLA-treated nonrestricted mice and from 91.3 +/- 1.5 to 94.5 +/- 1.0% (P < 0.05) in the restricted mice. The lower energy storage in the CLA-fed mice was accounted for by an increase in the energy expenditure (74%) and by an increase in energy lost in the excreta (26%). Feeding CLA also increased liver weight, which may warrant further studies on the safety of CLA. PMID:11983818

  8. Antisense oligonucleotides against the alpha-subunit of ENaC decrease lung epithelial cation-channel activity.

    PubMed

    Jain, L; Chen, X J; Malik, B; Al-Khalili, O; Eaton, D C

    1999-06-01

    Amiloride-sensitive Na+ transport by lung epithelia plays a critical role in maintaining alveolar Na+ and water balance. It has been generally assumed that Na+ transport is mediated by the amiloride-sensitive epithelial Na+ channel (ENaC) because molecular biology studies have confirmed the presence of ENaC subunits alpha, beta, and gamma in lung epithelia. However, the predominant Na+-transporting channel reported from electrophysiological studies by most laboratories is a nonselective, high-conductance channel that is very different from the highly selective, low-conductance ENaC reported in other tissues. In our laboratory, single-channel recordings from apical membrane patches from rat alveolar type II (ATII) cells in primary culture reveal a nonselective cation channel with a conductance of 20.6 +/- 1.1 pS and an Na+-to-K+ selectivity of 0.97 +/- 0.07. This channel is inhibited by submicromolar concentrations of amiloride. Thus there is some question about the relationship between the gene product observed with single-channel methods and the cloned ENaC subunits. We have employed antisense oligonucleotide methods to block the synthesis of individual ENaC subunit proteins (alpha, beta, and gamma) and determined the effect of a reduction in the subunit expression on the density of the nonselective cation channel observed in apical membrane patches on ATII cells. Treatment of ATII cells with antisense oligonucleotides inhibited the production of each subunit protein; however, single-channel recordings showed that only the antisense oligonucleotide targeting the alpha-subunit resulted in a significant decrease in the density of nonselective cation channels. Inhibition of the beta- and gamma-subunit proteins alone or together did not cause any changes in the observed channel density. There were no changes in open probability or other channel characteristics. These results support the hypothesis that the alpha-subunit of ENaC alone or in combination with some

  9. Luteinizing Hormone Reduces the Activity of the NPR2 Guanylyl Cyclase in Mouse Ovarian Follicles, Contributing to the Cyclic GMP Decrease that Promotes Resumption of Meiosis in Oocytes

    PubMed Central

    Robinson, Jerid W.; Zhang, Meijia; Shuhaibar, Leia C.; Norris, Rachael P.; Geerts, Andreas; Wunder, Frank; Eppig, John J.; Potter, Lincoln R.; Jaffe, Laurinda A.

    2012-01-01

    In preovulatory ovarian follicles of mice, meiotic prophase arrest in the oocyte is maintained by cyclic GMP from the surrounding granulosa cells that diffuses into the oocyte through gap junctions. The cGMP is synthesized in the granulosa cells by the transmembrane guanylyl cyclase natriuretic peptide receptor 2 (NPR2) in response to the agonist C-type natriuretic peptide (CNP). In response to luteinizing hormone (LH), cGMP in the granulosa cells decreases, and as a consequence, oocyte cGMP decreases and meiosis resumes. Here we report that within 20 minutes, LH treatment results in decreased guanylyl cyclase activity of NPR2, as determined in the presence of a maximally activating concentration of CNP. This occurs by a process that does not reduce the amount of NPR2 protein. We also show that by a slower process, first detected at 2 hours, LH decreases the amount of CNP available to bind to the receptor. Both of these LH actions contribute to decreasing cGMP in the follicle, thus signaling meiotic resumption in the oocyte. PMID:22546688

  10. Short-term energy restriction during late gestation of beef cows decreases postweaning calf humoral immune response to vaccination.

    PubMed

    Moriel, P; Piccolo, M B; Artioli, L F A; Marques, R S; Poore, M H; Cooke, R F

    2016-06-01

    haptoglobin concentrations on d 274, 276, and 279; and serum BVDV-1a titers on d 306 were less for REST calves than for CTRL calves ( ≤ 0.05). Hence, a NEm restriction to 70% of daily requirements during the last 40 d of gestation had minimal effects on cow precalving growth and did not affect postcalving cow growth and reproductive performance. However, it decreased postweaning vaccination-induced humoral immunity, inflammatory, and physiological stress responses of calves. PMID:27285930

  11. Acutely administered melatonin decreases somatostatin-binding sites and the inhibitory effect of somatostatin on adenylyl cyclase activity in the rat hippocampus.

    PubMed

    Izquierdo-Claros, Rosa María; Boyano-Adánez Md, María del Carmen; Arilla-Ferreiro, Eduardo

    2004-03-01

    Melatonin is known to increase neuronal activity in the hippocampus, an effect contrary to that of somatostatin (somatotropin release-inhibiting factor, SRIF). Thus, the aim of this study was to investigate whether the somatostatinergic system is implicated in the mechanism of action of melatonin in the rat hippocampus. One group of rats was injected a single dose of melatonin [25 microg/kg subcutaneously (s.c.)] or saline containing ethanol (0.5%, s.c.) and killed 5 hr later. Melatonin significantly decreased the SRIF-like immunoreactivity levels and induced a significant decrease in the density of SRIF receptors as well as in the dissociation constant (Kd). SRIF-mediated inhibition of basal and forskolin-stimulated adenylyl cyclase activity was markedly decreased in hippocampal membranes from melatonin-treated rats. The functional activity of Gi proteins was similar in hippocampal membranes from melatonin-treated and control rats. Western blot analyses revealed that melatonin administration did not alter Gialpha1 or Gialpha2 levels. To determine if the changes observed were related to melatonin-induced activation of central melatonin receptors, a melatonin receptor antagonist, luzindole, was administered prior to melatonin injection. Pretreatment with luzindole (10 mg/kg, s.c.) did not alter the melatonin-induced effects on the above-mentioned parameters and luzindole, alone, had no observable effect. The present results demonstrate that melatonin decreases the activity of the SRIF receptor-effector system in the rat hippocampus, an effect which is apparently not mediated by melatonin receptors. As SRIF exerts an opposite effect to that of melatonin on hippocampal neuronal activity, it is possible that the SRIFergic system could be implicated in the mechanism of action of melatonin in the rat.

  12. A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: decrease in mitochondrial DNA repair activity during ageing.

    PubMed

    Soerensen, Mette; Gredilla, Ricardo; Müller-Ohldach, Mathis; Werner, Alexandra; Bohr, Vilhelm A; Osiewacz, Heinz D; Stevnsner, Tinna

    2009-08-01

    The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.

  13. Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats.

    PubMed Central

    Kondo, H; Osborne, M L; Kolhouse, J F; Binder, M J; Podell, E R; Utley, C S; Abrams, R S; Allen, R H

    1981-01-01

    In man, use of the general anesthetic nitrous oxide, N2O, is associated with hematologic and neurologic abnormalities that mimic those seen in cobalamin (Cbl, vitamin B12) deficiency. We have measured a number of aspects of Cbl metabolism in rts exposed to various concentrations of N2O for various periods of time. As little as 2% N2O given for 15 h resulted in 30% inhibition of methionine synthetase (MS) in rat liver. With 50% N2O, inhibition of 70% occurred with 1 h and did not change during the next 48 h. Under these conditions, no inhibition of methylmalonyl-CoA mutase (MMCoAM) was observed. The recovery of MS activity was slow and was only 80% of control values 72 h after N2O was stopped. Studies employing rats previously injected with [57Co]Cbl showed that N2O displaced [57Co]Cbl from MS in a manner that temporally and quantitatively paralleled the loss of MS activity. Recovery of MS activity paralleled the reappearance of [57Co]Cbl on MS. N2O also caused the hepatic content of CH3-[57Co]Cbl to decrease by 20-60%. When [57Co]-Cbl was extracted from liver and analyzed by paper chromatography, [57Co]Cbl analogues were present (10-40% of total [57Co]Cbl) in rats exposed to N2O, but not in control animals. When rats were exposed to 50% N2O for 33 d, the total of endogenous Cbl and Cbl analogues in liver decreased to 35% of control values and endogenous Cbl decreased to 10% of control values. At this time, MS activity was 15% of control values and MMCoAM was only 26% of control values. We conclude that N2O causes multiple defects in Cbl metabolism that include the following: (a) rapid inhibition of MS activity with a slow recovery when N2O is stopped; (b) displacement of Cbl from MS; (c) decreased CH3-Cbl; (d) conversion of Cbl to Cbl analogues; (e) the gradual development of Cbl deficiency and (f) an eventual decrease in MMCoAM activity with a further decrease in MS activity. PMID:6112240

  14. Ligand reorganization and activation energies in nonadiabatic electron transfer reactions

    NASA Astrophysics Data System (ADS)

    Zhu, Jianjun; Wang, Jianji; Stell, George

    2006-10-01

    The activation energy and ligand reorganization energy for nonadiabatic electron transfer reactions in chemical and biological systems are investigated in this paper. The free energy surfaces and the activation energy are derived exactly in the general case in which the ligand vibration frequencies are not equal. The activation energy is derived by free energy minimization at the transition state. Our formulation leads to the Marcus-Hush [J. Chem. Phys. 24, 979 (1956); 98, 7170 (1994); 28, 962 (1958)] results in the equal-frequency limit and also generalizes the Marcus-Sumi [J. Chem. Phys. 84, 4894 (1986)] model in the context of studying the solvent dynamic effect on electron transfer reactions. It is found that when the ligand vibration frequencies are different, the activation energy derived from the Marcus-Hush formula deviates by 5%-10% from the exact value. If the reduced reorganization energy approximation is introduced in the Marcus-Hush formula, the result is almost exact.

  15. Simple Activity Demonstrates Wind Energy Principles

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2012-01-01

    Wind energy is an exciting and clean energy option often described as the fastest-growing energy system on the planet. With some simple materials, teachers can easily demonstrate its key principles in their classroom. (Contains 1 figure and 2 tables.)

  16. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes.

    PubMed

    Dere, E; De Souza-Silva, M A; Frisch, C; Teubner, B; Söhl, G; Willecke, K; Huston, J P

    2003-08-01

    Gap-junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell-type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap-junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30-/-, Cx30+/-, and Cx30+/+ mice in the open-field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30-/- mice showed reduced exploratory activity in terms of rearings but not locomotion in the open-field and object exploration task. Furthermore, Cx30-/- mice exhibited anxiogenic behaviour as shown by higher open-field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30-/- mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/- mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5-hydroxyindole acid (5-HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/- mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap-junctional signalling in behavioural processes.

  17. Histamine H3 receptor activation decreases kainate-induced hippocampal gamma oscillations in vitro by action potential desynchronization in pyramidal neurons

    PubMed Central

    Andersson, Richard; Lindskog, Maria; Fisahn, André

    2010-01-01

    The study of rhythmic electrical activity in slice preparations has generated important insights into neural network function. While the synaptic mechanisms involved in the generation of in vitro network oscillations have been studied widely, little is known about the modulatory influence exerted on rhythmic activity in neuronal networks by neuropeptides and biogenic amines. Gamma oscillations play an important role in cognitive processes and are altered or disrupted in disorders such as Alzheimer's disease (AD) and schizophrenia. Given the importance of gamma oscillations for learning, memory and cognition processes as well as the recent interest in histamine H3 receptors in the development of pro-cognitive drugs to treat disorders such as AD and schizophrenia, it is relevant to study the impact of histaminergic mechanisms on network gamma oscillations. Here we show for the first time a modulation of gamma oscillation by histaminergic mechanisms. Selective activation of the H3 receptor by R-α-methylhistamine significantly reduces the power of kainate-induced gamma oscillations, but not carbachol-induced gamma oscillations, in the rat hippocampal slice preparation without affecting oscillation frequency. This effect is neither caused by a decrease in excitatory or inhibitory postsynaptic currents, nor a decrease in cellular excitability. Instead, we find that the decrease in oscillation power following H3 receptor activation results from a desynchronization of pyramidal neuron action potential firing with regard to the local field potential oscillation cycle. Our data provide a possible mechanism of action for histamine in regulating gamma oscillations in the hippocampal network. PMID:20156850

  18. In vitro aging of rat lung cells. Downregulation of telomerase activity and continuous decrease of telomere length are not incompatible with malignant transformation.

    PubMed

    Petitot, Fabrice; Lebeau, Jérôme; Dano, Laurent; Lectard, Bruno; Altmeyer, Sandrine; Levalois, Céline; Chevillard, Sylvie

    2003-05-15

    Most normal mammalian somatic cells cultivated in vitro enter replicative senescence after a finite number of divisions, as a consequence of the progressive shortening of telomeres during proliferation that reflects one aspect of organism/cellular aging. The situation appears more complex in rodent cells due to physiological telomerase expression in most somatic normal tissues, great telomere length, and the difficulties of finding suitable in vitro culture conditions. To study in vitro aging of rat lung epithelial cells, we have developed primary culture conditions adapted to rat fresh lung explants and have studied for 1 year (50 passages) the changes in cellular proliferation and mortality, genetic instability, telomerase activity, telomere length, and tumorigenic potential. We have observed an absence of senescence and/or crisis, a transient genetic instability, the persistence of a differentiated Clara cell phenotype, a steady decrease in telomerase activity followed by a low residual activity together with a continuous decrease in telomere length, a constant rate of proliferation, and the acquisition of tumorigenic potential. The bypass of the growth arrest and the acquisition of long-term growth properties could be explained by the loss of p16(INK4a) expression, the ARF/p53 pathway not being altered. In conclusion, these results clearly indicate that, in rat lung epithelial cells, in vitro transformation and acquisition of tumorigenic properties can occur even if the telomere length is still decreasing and telomerase activity remains downregulated.

  19. Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in Neuroblastoma and Pediatric Sarcomas In vitro and In vivo

    PubMed Central

    Yan, Shuang; Li, Zhijie; Thiele, Carol J

    2013-01-01

    The IL-6/JAK/STAT pathway is a key signal transduction pathway implicated in the pathogenesis of many human cancers, suggesting that kinase inhibitors targeting JAK/STAT3 may have a broad spectrum of antitumor activity. AZD1480, a pharmacological JAK1/2 inhibitor, exhibits anti-tumor potency in multiple adult malignancies. To evaluate the efficacy of inhibition of JAK/STAT3 signal transduction pathway we assessed the activity of AZD1480 in pediatric malignancies using preclinical models of three highly malignant pediatric solid tumors: neuroblastoma (NB), rhabdomyosarcoma (RMS) and the Ewing Sarcoma Family Tumors (ESFT). In this study, we employed panels of biomedical and biological experiments to evaluate the in vitro and in vivo activity of AZD1480 in NB, RMS and ESFT. Our data indicate that AZD1480 blocks endogenous as well as IL-6 induced STAT3 activation. AZD1480 decreases cell viability in 7/7NB, 7/7RMS and 2/2 ESFT cell lines (median EC50 is 1.5 μM, ranging from 0.36-5.37μM). AZD1480 induces cell growth inhibition and caspase-dependent apoptosis in vitro and decreases expression of STAT3 target genes, including cell cycle regulators CyclinD1, 3 and CDC25A, anti-apoptotic genes Bcl-2 and survivin, the metastasis-related factor TIMP-1 and c-Myc. In vivo studies showed AZD1480 significantly decreased tumor growth and prolonged overall survival in tumor-bearing mice. Tumors from AZD1480-treated mice showed inhibition of activated STAT3 as well as decreased expression of STAT3 downstream targets. Our study provides strong evidence of the anti-tumor growth potency of JAK inhibitor AZD1480 in pediatric solid tumors, providing proof-of principle that inhibition of the JAK/STAT3 signal transduction could be a promising therapeutic target for high-risk pediatric solid tumors. PMID:23531921

  20. Central H3R activation by thioperamide does not affect energy balance.

    PubMed

    Sindelar, Dana K; Shepperd, Mary L; Pickard, Richard T; Alexander-Chacko, Jesline; Dill, M Joelle; Cramer, Jeffrey W; Smith, Dennis P; Gadski, Robert

    2004-06-01

    The central histamine 3 receptor (H3R) is a presynaptic autoreceptor that regulates neuronal release and synthesis of histamine, and is thought to play a key role in controlling numerous central nervous system (CNS)-mediated parameters, including energy homeostasis. Thioperamide, the prototypical selective H3R antagonist, was used to examine the role that H3R plays in regulating energy balance in vivo. Thioperamide was administered either intraperitoneally or orally to rats and the pharmacokinetic parameters were examined along with central H3R binding and histaminergic system activation. Food intake and metabolic parameters of either route of thioperamide administration were likewise examined. In a dose-dependent manner, both the intraperitoneal and oral route of administration resulted in similar ex vivo binding curves and tele-methylhistamine dose-response curves despite the route of administration. However, only intraperitoneal administration of 30 mg/kg thioperamide resulted in a significant decrease in 24-h food inta