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Sample records for activity increased approximately

  1. Approximate circuits for increased reliability

    SciTech Connect

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-08-18

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  2. Approximate circuits for increased reliability

    SciTech Connect

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-12-22

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  3. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  4. Increased Spreading Activation in Depression

    ERIC Educational Resources Information Center

    Foster, Paul S.; Yung, Raegan C.; Branch, Kaylei K.; Stringer, Kristi; Ferguson, Brad J.; Sullivan, William; Drago, Valeria

    2011-01-01

    The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of…

  5. Best possible approximation algorithms for single machine scheduling with increasing linear maintenance durations.

    PubMed

    Shi, Xuefei; Xu, Dehua

    2014-01-01

    We consider a single machine scheduling problem with multiple maintenance activities, where the maintenance duration function is of the linear form f(t) = a+bt with a ≥ 0 and b > 1. We propose an approximation algorithm named FFD-LS2I with a worst-case bound of 2 for problem. We also show that there is no polynomial time approximation algorithm with a worst-case bound less than 2 for the problem with b ≥ 0 unless P = NP, which implies that the FFD-LS2I algorithm is the best possible algorithm for the case b > 1 and that the FFD-LS algorithm, which is proposed in the literature, is the best possible algorithm for the case b ≤ 1 both from the worst-case bound point of view. PMID:24701177

  6. Classroom Activities: Increase the Challenge.

    ERIC Educational Resources Information Center

    Cote-Moran, Claudette

    Four classroom activities for second language learning are described. They include games and other exercises designed to enhance vocabulary development, review grammatical structures, encourage conversation on a variety of topics, and introduce cultural elements into instruction. All use materials that are readily available, and all are intended…

  7. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  8. On increasing the efficiency of the modified method of S-approximations

    NASA Astrophysics Data System (ADS)

    Stepanova, I. E.; Raevskiy, D. N.; Shchepetilov, A. V.

    2016-01-01

    An advanced method for solving the system of linear algebraic equations (SLAE) based on the application of Chebyshev polynomials is described. The modified S-approximations of the elements of gravity field are found by the efficient approaches applied to the solution of SLAE that describes the geophysically informative problem. The results of the mathematical experiment are presented.

  9. Exergames: Increasing Physical Activity through Effective Instruction

    ERIC Educational Resources Information Center

    Rudella, Jennifer L.; Butz, Jennifer V.

    2015-01-01

    Due to the growing obesity epidemic in the United States, educators must consider new ways to increase physical activity in an effort to address obesity. There are a variety of ways educators can increase physical activity in the classroom, and exergames--video games that require physical movement in order to play--are a modern-day approach to…

  10. Utilizing Wisconsin Afterschool Programs to Increase Physical Activity in Youth

    ERIC Educational Resources Information Center

    Cavanagh, Bradley D.; Meinen, Amy

    2015-01-01

    Background: Approximately 31.7% of children in the United States are overweight or obese. Interventions in the afterschool setting may help combat childhood obesity. Research exists on interventions in school settings, but a few data exist for interventions about afterschool programs. This study investigates increasing physical activity (PA) in…

  11. Increased alveolar plasminogen activator in early asbestosis

    SciTech Connect

    Cantin, A.; Allard, C.; Begin, R.

    1989-03-01

    Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.

  12. Increased Ribozyme Activity in Crowded Solutions*

    PubMed Central

    Desai, Ravi; Kilburn, Duncan; Lee, Hui-Ting; Woodson, Sarah A.

    2014-01-01

    Noncoding RNAs must function in the crowded environment of the cell. Previous small-angle x-ray scattering experiments showed that molecular crowders stabilize the structure of the Azoarcus group I ribozyme, allowing the ribozyme to fold at low physiological Mg2+ concentrations. Here, we used an RNA cleavage assay to show that the PEG and Ficoll crowder molecules increased the biochemical activity of the ribozyme, whereas sucrose did not. Crowding lowered the Mg2+ threshold at which activity was detected and increased total RNA cleavage at high Mg2+ concentrations sufficient to fold the RNA in crowded or dilute solution. After correcting for solution viscosity, the observed reaction rate was proportional to the fraction of active ribozyme. We conclude that molecular crowders stabilize the native ribozyme and favor the active structure relative to compact inactive folding intermediates. PMID:24337582

  13. Addressing childhood obesity through increased physical activity.

    PubMed

    Hills, Andrew P; Okely, Anthony D; Baur, Louise A

    2010-10-01

    Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today's young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive 'shame and blame' mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter) lives than their parents. PMID:20736922

  14. Tooth Bleaching Increases Dentinal Protease Activity

    PubMed Central

    Sato, C.; Rodrigues, F.A.; Garcia, D.M.; Vidal, C.M.P.; Pashley, D.H.; Tjäderhane, L.; Carrilho, M.R.; Nascimento, F.D.; Tersariol, I.L.S.

    2012-01-01

    Hydrogen peroxide is an oxidative agent commonly used for dental bleaching procedures. The structural and biochemical responses of enamel, dentin, and pulp tissues to the in vivo bleaching of human (n = 20) premolars were investigated in this study. Atomic force microscopy (AFM) was used to observe enamel nanostructure. The chemical composition of enamel and dentin was analyzed by infrared spectroscopy (FTIR). The enzymatic activities of dental cathepsin B and matrix metalloproteinases (MMPs) were monitored with fluorogenic substrates. The amount of collagen in dentin was measured by emission of collagen autofluorescence with confocal fluorescence microscopy. The presence of Reactive Oxygen Species (ROS) in the pulp was evaluated with a fluorogenic 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) probe. Vital bleaching of teeth significantly altered all tested parameters: AFM images revealed a corrosion of surface enamel nanostructure; FTIR analysis showed a loss of carbonate and proteins from enamel and dentin, along with an increase in the proteolytic activity of cathepsin-B and MMPs; and there was a reduction in the autofluorescence of collagen and an increase in both cathepsin-B activity and ROS in pulp tissues. Together, these results indicate that 35% hydrogen peroxide used in clinical bleaching protocols dramatically alters the structural and biochemical properties of dental hard and soft pulp tissue. PMID:23242228

  15. Single-Active-Electron Approximation for Describing Molecules in Ultrashort Laser Pulses

    NASA Astrophysics Data System (ADS)

    Saenz, Alejandro; Awasthi, Manohar; Vanne, Yulian; Castro, Alberto; Decleva, Piero

    2008-05-01

    A numerical approach that allows for the solution of the time-dependent Schr"odinger equation (TDSE) describing molecules exposed to intense short laser pulses was developed. The molecular response to the strong field is described within the single-active electron approximation (SAE). The method is applied to molecular hydrogen and the validity of the SAE is investigated by comparing the ionization and electronic excitation yields to full two-electron solutions of the TDSE. The present results are also used to investigate the validity of approximate SAE methods like the molecular Ammosov-Delone-Krainov and the strong-field approximation. Finally, results for larger molecules like O2, N2, and C2H2 (acetylene) are presented.

  16. School Programs to Increase Physical Activity

    ERIC Educational Resources Information Center

    Lee, Amelia; Solmon, Melinda

    2007-01-01

    A quality physical education program is at the heart of any plan to promote lifelong participation in physical activity, but it has become evident at many schools that physical education specialists alone cannot address the physical activity needs of children. This is why a series of studies were conducted to develop strategies for the…

  17. Increasing Physical Activity through Recess. Research Brief

    ERIC Educational Resources Information Center

    Beighle, Aaron

    2012-01-01

    Regular physical activity promotes important health benefits, reduces risk for obesity and is linked with enhanced academic performance among students. The U.S. Surgeon General recommends that children engage in at least 60 minutes of moderate physical activity most days of the week, yet fewer than half of children ages 6 to 11 meet that…

  18. How Active Are Your Students? Increasing Physical Activity in Schools

    ERIC Educational Resources Information Center

    Avery, Marybell; Brandt, Janet

    2010-01-01

    The U. S. Department of Health and Human Services recommends that youth engage in at least 60 minutes of physical activity each day, most of which should be either moderate- or vigorous-intensity aerobic physical activity. Half of this amount (30 minutes) should be achieved during the school day. NASPE provides guidance in the form of a…

  19. The DHHC palmitoyltransferase approximated regulates Fat signaling and Dachs localization and activity.

    PubMed

    Matakatsu, Hitoshi; Blair, Seth S

    2008-09-23

    Signaling via the large protocadherin Fat (Ft), regulated in part by its binding partner Dachsous (Ds) and the Golgi-resident kinase Four-jointed (Fj), is required for a variety of developmental functions in Drosophila. Ft and, to a lesser extent, Ds suppress overgrowth of the imaginal discs from which appendages develop and regulate the Hippo pathway [1-5] (reviewed in [6]). Ft, Ds, and Fj are also required for normal planar cell polarity (PCP) in the wing, abdomen, and eye and for the normal patterning of appendages, including the spacing of crossveins in the wing and the segmentation of the leg tarsus (reviewed in [7-9]). Ft signaling was recently shown to be negatively regulated by the atypical myosin Dachs [10, 11]. We identify here an additional negative regulator of Ft signaling in growth control, PCP, and appendage patterning, the Approximated (App) protein. We show that App encodes a member of the DHHC family, responsible for the palmitoylation of selected cytoplasmic proteins, and provide evidence that App acts by controlling the normal subcellular localization and activity of Dachs. PMID:18804377

  20. Rational positive real approximations for LQG optimal compensators arising in active stabilization of flexible structures

    NASA Technical Reports Server (NTRS)

    Desantis, A.

    1994-01-01

    In this paper the approximation problem for a class of optimal compensators for flexible structures is considered. The particular case of a simply supported truss with an offset antenna is dealt with. The nonrational positive real optimal compensator transfer function is determined, and it is proposed that an approximation scheme based on a continued fraction expansion method be used. Comparison with the more popular modal expansion technique is performed in terms of stability margin and parameters sensitivity of the relative approximated closed loop transfer functions.

  1. NIMS Observes Increased Activity at Loki Patera, Io

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Loki Patera, historically the most active and persistent hot spot on Io, is located on the hemisphere of Io always facing Jupiter. Loki Patera was the site of two plumes during the Voyager encounters, which were not seen during the early orbits of Galileo. Ground-based observers reported Loki Patera to be unusually dim during this time, marking a period of low volcanic activity.

    On 21 February 1997, during Galileo's sixth orbit, the Near Infrared Mapping Spectrometer (NIMS) on the Galileo spacecraft observed Io in daylight from a range of approximately 703,000 km (440,000 miles). The image on the left shows Io at a wavelength of 2.95 microns. Loki Patera is seen to be relatively quiescent (at longer wavelengths which are more sensitive to thermal emission, Loki Patera is more noticeable).

    A few weeks later, on March 12th 1997, ground based observers using the Infra-Red Telescope Facility (IRTF) on Mauna Kea, Hawaii, observed an intense brightening in the Loki region, so much that Loki was contributing 75% of Io's in-eclipse flux for this hemisphere. A large eruption was taking place! Other ground-based observations through March, April and May tracked the course of the activity and confirmed its location at Loki Patera.

    On 4 April 1997, NIMS again observed Io during the seventh orbit from a range of 556,000 km (348,000 miles), with Loki Patera positioned in darkness, close to the limb. The image on the right shows the increase in activity at Loki Patera, again at 2.95 microns. A preliminary single temperature fit to NIMS orbit seven Loki Patera hot spot data yields a temperature of 500 K and an area of over 800 square kilometers. That the image is so bright at this wavelength is an indication of the areal extent of the activity. It is also probable that some part of the volcanic material being erupted or exposed is at considerably higher temperatures than that of the 500 K single-temperature fit.

    Io is under observation by ground-based observers under

  2. Gain-Scheduled Approximations to H-Infinity Controllers for the F/A-18 Active Aeroelastic Wing

    NASA Technical Reports Server (NTRS)

    Lind, Rick

    1999-01-01

    The Active Aeroelastic Wing will demonstrate technologies related to aeroservoelastic effects such as wing twist and load minimization. This paper presents a control design based on H-infinity synthesis that simultaneously considers the multiple objectives associated with handling qualities, actuator limitations, and loads. The controller is realized as a filter and gain set approximation to a state-space H-infinity controller. This approximation allows scheduling of the controller over a flight envelope.

  3. Best Practices and Recommendations for Increasing Physical Activity in Youth

    ERIC Educational Resources Information Center

    Erwin, Heather; Beets, Michael W.; Centeio, Erin; Morrow, James R., Jr.

    2014-01-01

    Many efforts to increase the physical activity levels of Americans have been introduced and implemented over the past 20 years. National Physical Activity Guidelines have been established, and the National Physical Activity Plan (NPAP) is now in place, which includes a specific sector dedicated to education. This article addresses the Education…

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

    PubMed Central

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

    2013-01-01

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

  5. Jealousy increased by induced relative left frontal cortical activity.

    PubMed

    Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2015-10-01

    Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. PMID:25844975

  6. Building a better mousetrap (exergame) to increase youth physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While exergames have been demonstrated to induce moderate levels of physical activity (PA) if played as designed, there is conflicting evidence on use of exergaming leading to increased habitual PA. Exergames have increased PA in some home and school studies, but not others. Exergames have been us...

  7. Development of an active boring bar for increased chatter immunity

    SciTech Connect

    Redmond, J.; Barney, P.; Smith, D.

    1997-03-01

    The development and initial evaluation of a prototype boring bar featuring active vibration control for increased chatter immunity is described. The significance of active damping both normal and tangential to the workpiece surface is evaluated, indicating the need for two axis control to ensure adequate performance over expected variations in tool mounting procedures. The prototype tool features a commercially available boring bar modified to accommodate four PZT stack actuators for two axis bending control. Measured closed-loop dynamics are combined with a computer model of the boring process to simulate increased metal removal rate and improved workpiece surface finish through active control.

  8. Large plasmaspheric electric fields at L approximately 2 measured by the S3-3 satellite during strong geomagnetic activity

    NASA Technical Reports Server (NTRS)

    Gonzalez, W. D.; Pinto, O., Jr.; Mendes, O., Jr.; Mozer, F. S.

    1986-01-01

    Large plasmaspheric electric fields at L is approximately 2 measured by the S3-3 satellite during strong geomagnetic activity are reported. Since these measurements have amplitudes comparable to those of the local corotation electric field, during such events the plasmasphere is expected to get strongly altered event at such low L-values. Furthermore, those measurements could contribute to the understanding of the physics of the convection/electric field penetration to the low latitude plasmaphere as well as the disturbed dynamo, during strong geomagnetic activity. For this purpose, critical parameters related to geomagnetic activity are also presented for the reported electric field events.

  9. Cerebellar fMRI Activation Increases with Increasing Working Memory Demands.

    PubMed

    Küper, M; Kaschani, P; Thürling, M; Stefanescu, M R; Burciu, R G; Göricke, S; Maderwald, S; Ladd, M E; Hautzel, H; Timmann, D

    2016-06-01

    The aim of the present study was to explore cerebellar contributions to the central executive in n-back working memory tasks using 7-T functional magnetic imaging (fMRI). We hypothesized that cerebellar activation increased with increasing working memory demands. Activations of the cerebellar cortex and dentate nuclei were compared between 0-back (serving as a motor control task), 1-back, and 2-back working memory tasks for both verbal and abstract modalities. A block design was used. Data of 27 participants (mean age 26.6 ± 3.8 years, female/male 12:15) were included in group statistical analysis. We observed that cerebellar cortical activations increased with higher central executive demands in n-back tasks independent of task modality. As confirmed by subtraction analyses, additional bilateral activations following higher executive demands were found primarily in four distinct cerebellar areas: (i) the border region of lobule VI and crus I, (ii) inferior parts of the lateral cerebellum (lobules crus II, VIIb, VIII, IX), (iii) posterior parts of the paravermal cerebellar cortex (lobules VI, crus I, crus II), and (iv) the inferior vermis (lobules VI, VIIb, VIII, IX). Dentate activations were observed for both verbal and abstract modalities. Task-related increases were less robust and detected for the verbal n-back tasks only. These results provide further evidence that the cerebellum participates in an amodal bilateral neuronal network representing the central executive during working memory n-back tasks. PMID:26202670

  10. Increasing physical activity through mobile device interventions: A systematic review.

    PubMed

    Muntaner, Adrià; Vidal-Conti, Josep; Palou, Pere

    2016-09-01

    Physical inactivity is a health problem that affects people worldwide and has been identified as the fourth largest risk factor for overall mortality (contributing to 6% of deaths globally). Many researchers have tried to increase physical activity levels through traditional methods without much success. Thus, many researchers are turning to mobile technology as an emerging method for changing health behaviours. This systematic review sought to summarise and update the existing scientific literature on increasing physical activity through mobile device interventions, taking into account the methodological quality of the studies. The articles were identified by searching the PubMed, SCOPUS and SPORTDiscus databases for studies published between January 2003 and December 2013. Studies investigating efforts to increase physical activity through mobile phone or even personal digital assistant interventions were included. The search results allowed the inclusion of 11 studies that gave rise to 12 publications. Six of the articles included in this review reported significant increases in physical activity levels. The number of studies using mobile devices for interventions has increased exponentially in the last few years, but future investigations with better methodological quality are needed to draw stronger conclusions regarding how to increase physical activity through mobile device interventions. PMID:25649783

  11. [Increase of physical activity by improvement of the nutritional status].

    PubMed

    Torún, B

    1989-09-01

    Physical activity is affected by nutritional modifications and, in turn, influences growth, cognition, social behavior, work performance and other functions. Studies in preschool children showed that: 1. A decrease in energy intake during four to seven days reduced the time allocated to energy-demanding activities and increased sedentary activities. 2. Children with mild weight deficit were more sedentary than well-nourished counterparts. 3. Children became more active when nutritional status improved. 4. A 10% reduction in energy intake reduced total energy expenditure by 15% without affecting weight gain nor basal metabolism. Studies of men working in non-mechanized agriculture showed that: 1. Dietary improvements led to faster salaried work, reduction of napping time and greater physical activity after work. 2. An increase in energy intake increased total daily energy expenditure, tending to maintain energy balance and relatively stable body weight within the cyclic variations of the agricultural year. 3. Food supplementation did not necessarily improve productivity. Other labor incentives without dietary improvements increased energy expenditure during working hours, which resulted in weight loss. In conclusion, good health and nutrition provide the biological basis for adequate physical activity that may improve cognitive development, social interactions, economic productivity and the quality of life of an individual or a population, but other incentives are required for the optimal expression of that biologic potential. PMID:2518785

  12. Walking with wider steps increases stance phase gluteus medius activity

    PubMed Central

    Kubinski, Samantha N.; McQueen, Christina A.; Sittloh, Keir A.; Dean, Jesse C.

    2014-01-01

    Increases in step width have been reported for several clinical populations, including older adults and stroke survivors. These populations often also exhibit decreased hip abductor strength, suggesting that walking with wider steps may be an adaptive response in order to reduce the mechanical demands on the hip abductors. The purpose of this study was to quantify the relationship between step width and gluteus medius (GM) activity during walking. Fourteen young, uninjured adults walked on a treadmill at 1.25 m/s for four step width conditions (Normal, Narrow, Medium, and Wide) while step width and stance phase GM electromyographic (EMG) activity were quantified. We also measured hip abduction torque and GM activity during maximum voluntary isometric contractions (MVICs) at three hip angles (neutral, abducted 10°, and abducted 20°). During walking trials, GM activity was significantly (p<0.0001) influenced by step width; compared to Normal walking, GM activity was 47% higher with Wide steps and 24% lower with Narrow steps. We also observed a weak positive correlation (r=0.18±0.14) between step width and GM activity during Normal walking, as GM activity was higher with wider steps. These results cannot be attributed to changes in GM conformation under the recording electrode, as GM activity was not influenced by hip angle during MVICs. The increased GM activity with wider steps does not support the proposal that increasing step width would be a beneficial adaptation to weakened hip abductors. A likely alternative explanation is that increased step width is a response to decreased gait balance. PMID:25300241

  13. [Increased antibacterial activity of antibiotics with etonium in vitro].

    PubMed

    Petrunyk, I O

    2000-01-01

    The activity of compositions of antibiotics cefasolin, benzylpenicillin and gentamycin with etonium in respect to museum strains Staphylococcus aureus 209, Escherichia coli K-12, Proteus vulgaris 410, P. mirabilis, Pseudomonas aeruginosa 19, Klebsiella pneumoniae 5054 and polyresistance strains S. aureus, E. coli, P. mirabilis in vitro was researched. The increase of the compositions activity as a result of synergy in the action of their component 4 up to 4496 times has been established. PMID:11421003

  14. Increasing Arabian dust activity and the Indian Summer Monsoon

    NASA Astrophysics Data System (ADS)

    Solmon, F.; Nair, V. S.; Mallet, M.

    2015-02-01

    Over the past decade, Aerosol Optical Depth (AOD) observations based on satellite and ground measurements have shown a significant increase over Arabia and the Arabian Sea, attributed to an intensification of regional dust activity. Recent studies have also suggested that west Asian dust forcing could induce a positive response of Indian monsoon precipitations on a weekly time scale. Using observations and a regional climate model including interactive slab ocean and dust aerosol schemes, the present study investigates possible climatic links between the increasing June-July-August-September (JJAS) Arabian dust activity and precipitation trends over southern India during the 2000-2009 decade. Meteorological reanalysis and AOD observations suggest that the observed decadal increase of dust activity and a simultaneous intensification of summer precipitation trend over southern India are both linked to a deepening of JJAS surface pressure conditions over the Arabian Sea. We show that the model skills in reproducing this trends and patterns are significantly improved only when an increasing dust emission trend is imposed on the basis of observations. We conclude that although climate variability might primarily determine the observed regional pattern of increasing dust activity and precipitation during the 2000-2009 decade, the associated dust radiative forcing might however induce a critical dynamical feedback contributing to enhanced regional moisture convergence and JJAS precipitation over Southern India.

  15. Local school policies increase physical activity in Norwegian secondary schools

    PubMed Central

    Haug, Ellen; Torsheim, Torbjørn; Samdal, Oddrun

    2010-01-01

    SUMMARY The implementation of school policies to support the adoption of physical activity is one of the main strategies recommended to increase physical activity levels among this age group. However, documentation of the effect of such policies is so far limited. The purpose of this study was to explore policy-related practices to support physical activity in Norwegian secondary schools and their association with recess physical activity. Emphasis was given to examine the association between policies and physical activity, over and beyond, individual level interests and environmental factors and to examine cross-level interaction effects. This cross-sectional study was based on a nationally representative sample of Norwegian secondary schools and grade 8 students who participated in the Health Behaviour in School-aged Children (HBSC) 2005/06 study. The final sample comprised 68 schools and 1347 students. Data were collected through questionnaires. The results showed that schools with a written policy for physical activity and schools offering organized non-curricular physical activity several times a week had a higher proportion of students reporting daily participation in recess physical activity. Multilevel logistic regression analysis demonstrated a cross-level main effect of the policy index after controlling for sex, socio-economic status, individual-level interests and the physical environment. A significant contribution of adding the policy index to the prediction of recess physical activity above that provided by the individual-level interests and the physical environment was demonstrated. The results are encouraging and give scientific support to policy documents recommending the implementation of school policies to increase physical activity. PMID:19884244

  16. Changing the School Environment to Increase Physical Activity in Children

    PubMed Central

    Lanningham-Foster, Lorraine; Foster, Randal C.; McCrady, Shelly K.; Manohar, Chinmay; Jensen, Teresa B.; Mitre, Naim G.; Hill, James O.; Levine, James A.

    2009-01-01

    OBJECTIVE We examined the hypothesis that elementary school-age children will be more physically active while attending school in a novel, activity-permissive school environment compared to their traditional school environment RESEARCH METHODS AND PROCEDURES Twenty-four children were monitored with a single triaxial accelerometer worn on the thigh. The students attended school in three different environments: traditional school with chairs and desks, an activity-permissive environment, and finally their traditional school with desks which encouraged standing. Data from the school children was compared with another group of age-matched children (n = 16) whose physical activity was monitored during summer vacation. RESULTS When children attended school in their traditional environment, they moved an average (mean ± standard deviation) 71 ± 0.4 m/s2. When the children attended school in the activity-permissive environment, they moved an average of 115 ± 3 m/s2. The children moved 71 ± 0.7 m/s2 while attending the traditional school with standing desks. Children moved significantly more while attending school in the activity-permissive environment compared to the amount that they moved in either of the traditional school environments (P<0.0001 for both). Comparing children’s activity while they were on summer vacation (113 ± 8 m/s2) to school-bound children in their traditional environment showed significantly more activity for the children on summer vacation (P<0.0001). The school children in the activity-permissive environment were as active as children on summer vacation. DISCUSSION Children will move more in an activity-permissive environment. Strategies to increase the activity of school children may involve re-designing the school itself. PMID:18535550

  17. Using the Web to Increase Physical Activity in College Students

    ERIC Educational Resources Information Center

    Magoc, Dejan; Tomaka, Joe; Bridges-Arzaga, Amber

    2011-01-01

    Objectives: To evaluate the effectiveness of a theoretically based and Web-delivered intervention using common course technology for increasing physical activity in a college student sample. Methods: One hundred four students randomly participated in either a Web-based intervention involving 7 theory-based learning lessons or a control group that…

  18. Texting to increase adolescent physical activity: Feasibility assessment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Feasibility trials assess whether a behavior change program warrants a definite trial evaluation. This paper reports the feasibility of an intervention consisting of Self Determination Theory-informed text messages, pedometers, and goal prompts to increase adolescent physical activity. A 4-group ran...

  19. Games for increasing physical activity: Mechanisms for change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A small conference was held in Houston, TX, in May 2014, to address how to enhance exergames to increase physical activity. Several leading researchers were asked to address specific topics. Attendees came from across the globe. This Games for Health Journal Special Issue is devoted to sharing the a...

  20. Reduced Frontal Activation with Increasing 2nd Language Proficiency

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  1. Hypocholesterolemia in chronic anemias with increased erythropoietic activity.

    PubMed

    Shalev, Hanna; Kapelushnik, Joseph; Moser, Asher; Knobler, Hilla; Tamary, Hannah

    2007-03-01

    Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon. PMID

  2. Increased matriptase zymogen activation in inflammatory skin disorders

    PubMed Central

    Chen, Cheng-Jueng; Wu, Bai-Yao; Tsao, Pai-In; Chen, Chi-Yung; Wu, Mei-Hsuan; Chan, Yee Lam E.; Lee, Herng-Sheng; Johnson, Michael D.; Eckert, Richard L.; Chen, Ya-Wen; Chou, Fengpai; Lin, Chen-Yong

    2011-01-01

    Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H2O2 and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases. PMID:21123732

  3. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2013-10-01

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  4. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-05-27

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  5. Methods of increasing secretion of polypeptides having biological activity

    SciTech Connect

    Merino, Sandra

    2014-10-28

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  6. Methods of increasing secretion of polypeptides having biological activity

    SciTech Connect

    Merino, Sandra

    2015-04-14

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  7. Plant species richness increases phosphatase activities in an experimental grassland

    NASA Astrophysics Data System (ADS)

    Hacker, Nina; Wilcke, Wolfgang; Oelmann, Yvonne

    2014-05-01

    Plant species richness has been shown to increase aboveground nutrient uptake requiring the mobilization of soil nutrient pools. For phosphorus (P) the underlying mechanisms for increased P release in soil under highly diverse grassland mixtures remain obscure because aboveground P storage and concentrations of inorganic and organic P in soil solution and differently reactive soil P pools are unrelated (Oelmann et al. 2011). The need of plants and soil microorganisms for P can increase the exudation of enzymes hydrolyzing organically bound P (phosphatases) which might represent an important release mechanism of inorganic P in a competitive environment such as highly diverse grassland mixtures. Our objectives were to test the effects of i) plant functional groups (legumes, grasses, non-leguminous tall and small herbs), and of (ii) plant species richness on microbial P (Pmic) and phosphatase activities in soil. In autumn 2013, we measured Pmic and alkaline phosphomonoesterase and phosphodiesterase activities in soil of 80 grassland mixtures comprising different community compositions and species richness (1, 2, 4, 8, 16, 60) in the Jena Experiment. In general, Pmic and enzyme activities were correlated (r = 0.59 and 0.46 for phosphomonoesterase and phosphodiesterase activities, respectively; p

  8. Increases and fluctuations in thermal activity at Mount Wrangell, Alaska

    SciTech Connect

    Motyka, R.J.

    1983-01-01

    The objectives of this study were to document and interpret changes in thermal activity at two of three craters located on the rim of the ice-filled summit caldera of Mount Wrangell, an active glacier-clad shield volcano in south-central Alaska. The technique of glacier calorimetry was developed, through which changes in the volume of glacier ice in the craters and caldera were measured and related to changes in heat flow. Chemical analysis of gases and acid-thermal waters provided information on the underlying heat source. In 1965, thermal activity began increasing at both the North and West Craters. During the ensuing years, heat flow increased significantly at the North Crater, although in a highly fluctuating manner, while gradually declining at the West Crater. Pulses in heat flow at the North Crater occurred in 1966-68 and 1972-74, with both pulses followed by a four year decline in activity. Increases in heat flow began again in 1978-79 and have continued unabated through the summer of 1983. Over 80% of the 4.4 x 10/sup 7/m/sup 3/ ice volume within the crater in 1966 was melted by 1982, and the meltwaters have drained or evaporated from the crater. The subsequent rapid development of numerous fumaroles, the large dry-gas proportion of SO/sub 2/ (27%), and the inferred presence of gaseous HCl indicate that a shallow degassing magma body is the source of heat driving the thermal system. Seismically induced fracturing above the magma body is hypothesized to explain the initial increases in thermal activity.

  9. Increasing Arabian dust activity and the Indian summer monsoon

    NASA Astrophysics Data System (ADS)

    Solmon, F.; Nair, V. S.; Mallet, M.

    2015-07-01

    Over the past decade, aerosol optical depth (AOD) observations based on satellite and ground measurements have shown a significant increase over Arabia and the Arabian Sea, attributed to an intensification of regional dust activity. Recent studies have also suggested that west Asian dust forcing could induce a positive response of Indian monsoon precipitations on a weekly timescale. Using observations and a regional climate model including interactive slab-ocean and dust aerosol schemes, the present study investigates possible climatic links between the increasing June-July-August-September (JJAS) Arabian dust activity and precipitation trends over southern India during the 2000-2009 decade. Meteorological reanalysis and AOD observations suggest that the observed decadal increase of dust activity and a simultaneous intensification of summer precipitation trend over southern India are both linked to a deepening of JJAS surface pressure conditions over the Arabian Sea. In the first part of the study, we analyze the mean climate response to dust radiative forcing over the domain, discussing notably the relative role of Arabian vs. Indo-Pakistani dust regions. In the second part of the study, we show that the model skills in reproducing regional dynamical patterns and southern Indian precipitation trends are significantly improved only when an increasing dust emission trend is imposed on the basis of observations. We conclude that although interannual climate variability might primarily determine the observed regional pattern of increasing dust activity and precipitation during the 2000-2009 decade, the associated dust radiative forcing might in return induce a critical dynamical feedback contributing to enhancing regional moisture convergence and JJAS precipitations over southern India.

  10. Plant diversity increases soil microbial activity and soil carbon storage.

    PubMed

    Lange, Markus; Eisenhauer, Nico; Sierra, Carlos A; Bessler, Holger; Engels, Christoph; Griffiths, Robert I; Mellado-Vázquez, Perla G; Malik, Ashish A; Roy, Jacques; Scheu, Stefan; Steinbeiss, Sibylle; Thomson, Bruce C; Trumbore, Susan E; Gleixner, Gerd

    2015-01-01

    Plant diversity strongly influences ecosystem functions and services, such as soil carbon storage. However, the mechanisms underlying the positive plant diversity effects on soil carbon storage are poorly understood. We explored this relationship using long-term data from a grassland biodiversity experiment (The Jena Experiment) and radiocarbon ((14)C) modelling. Here we show that higher plant diversity increases rhizosphere carbon inputs into the microbial community resulting in both increased microbial activity and carbon storage. Increases in soil carbon were related to the enhanced accumulation of recently fixed carbon in high-diversity plots, while plant diversity had less pronounced effects on the decomposition rate of existing carbon. The present study shows that elevated carbon storage at high plant diversity is a direct function of the soil microbial community, indicating that the increase in carbon storage is mainly limited by the integration of new carbon into soil and less by the decomposition of existing soil carbon. PMID:25848862

  11. Semi-active damping with negative stiffness for multi-mode cable vibration mitigation: approximate collocated control solution

    NASA Astrophysics Data System (ADS)

    Weber, F.; Distl, H.

    2015-11-01

    This paper derives an approximate collocated control solution for the mitigation of multi-mode cable vibration by semi-active damping with negative stiffness based on the control force characteristics of clipped linear quadratic regulator (LQR). The control parameters are derived from optimal modal viscous damping and corrected in order to guarantee that both the equivalent viscous damping coefficient and the equivalent stiffness coefficient of the semi-active cable damper force are equal to their desired counterparts. The collocated control solution with corrected control parameters is numerically validated by free decay tests of the first four cable modes and combinations of these modes. The results of the single-harmonic tests demonstrate that the novel approach yields 1.86 times more cable damping than optimal modal viscous damping and 1.87 to 2.33 times more damping compared to a passive oil damper whose viscous damper coefficient is optimally tuned to the targeted mode range of the first four modes. The improvement in case of the multi-harmonic vibration tests, i.e. when modes 1 and 3 and modes 2 and 4 are vibrating at the same time, is between 1.55 and 3.81. The results also show that these improvements are obtained almost independent of the cable anti-node amplitude. Thus, the proposed approximate real-time applicable collocated semi-active control solution which can be realized by magnetorheological dampers represents a promising tool for the efficient mitigation of stay cable vibrations.

  12. Active learning increases student performance in science, engineering, and mathematics.

    PubMed

    Freeman, Scott; Eddy, Sarah L; McDonough, Miles; Smith, Michelle K; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-06-10

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes--although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms. PMID:24821756

  13. Active learning increases student performance in science, engineering, and mathematics

    PubMed Central

    Freeman, Scott; Eddy, Sarah L.; McDonough, Miles; Smith, Michelle K.; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-01-01

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes—although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms. PMID:24821756

  14. An active loudness model suggesting tinnitus as increased central noise and hyperacusis as increased nonlinear gain

    PubMed Central

    Zeng, Fan-Gang

    2012-01-01

    The present study uses a systems engineering approach to delineate the relationship between tinnitus and hyperacusis as a result of either hearing loss in the ear or an imbalanced state in the brain. Specifically examined is the input–output function, or loudness growth as a function of intensity in both normal and pathological conditions. Tinnitus reduces the output dynamic range by raising the floor, while hyperacusis reduces the input dynamic range by lowering the ceiling or sound tolerance level. Tinnitus does not necessarily steepen the loudness growth function but hyperacusis always does. An active loudness model that consists of an expansion stage following a compression stage can account for these key properties in tinnitus and hyperacusis loudness functions. The active loudness model suggests that tinnitus is a result of increased central noise, while hyperacusis is due to increased nonlinear gain. The active loudness model also generates specific predictions on loudness growth in tinnitus, hyperacusis, hearing loss or any combinations of the three conditions. These predictions need to be verified by experimental data and have explicit implications for treatment of tinnitus and hyperacusis. PMID:22641191

  15. Increasing the Thermal Conductivity of Graphene-Polyamide-6,6 Nanocomposites by Surface-Grafted Polymer Chains: Calculation with Molecular Dynamics and Effective-Medium Approximation.

    PubMed

    Gao, Yangyang; Müller-Plathe, Florian

    2016-02-25

    By employing reverse nonequilibrium molecular dynamics simulations in a full atomistic resolution, the effect of surface-grafted chains on the thermal conductivity of graphene-polyamide-6.6 (PA) nanocomposites has been investigated. The interfacial thermal conductivity perpendicular to the graphene plane is proportional to the grafting density, while it first increases and then saturates with the grafting length. Meanwhile, the intrinsic in-plane thermal conductivity of graphene drops sharply as the grafting density increases. The maximum overall thermal conductivity of nanocomposites appears at an intermediate grafting density because of these two competing effects. The thermal conductivity of the composite parallel to the graphene plane increases with the grafting density and grafting length which is attributed to better interfacial coupling between graphene and PA. There exists an optimal balance between grafting density and grafting length to obtain the highest interfacial and parallel thermal conductivity. Two empirical formulas are suggested, which quantitatively account for the effects of grafting length and density on the interfacial and parallel thermal conductivity. Combined with effective medium approximation, for ungrafted graphene in random orientation, the model overestimates the thermal conductivity at low graphene volume fraction (f < 10%) compared with experiments, while it underestimates it at high graphene volume fraction (f > 10%). For unoriented grafted graphene, the model matches the experimental results well. In short, this work provides some valuable guides to obtain the nanocomposites with high thermal conductivity by grafting chain on the surface of graphene. PMID:26800434

  16. JAK-2 V617F mutation increases heparanase procoagulant activity.

    PubMed

    Kogan, Inna; Chap, Dafna; Hoffman, Ron; Axelman, Elena; Brenner, Benjamin; Nadir, Yona

    2016-01-01

    Patients with polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) are at increased risk of arterial and venous thrombosis. In patients with ET a positive correlation was observed between JAK-2 V617F mutation, that facilitates erythropoietin receptor signalling, and thrombotic events, although the mechanism involved is not clear. We previously demonstrated that heparanase protein forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF) which leads to increased factor Xa production and subsequent activation of the coagulation system. The present study was aimed to evaluate heparanase procoagulant activity in myeloproliferative neoplasms. Forty bone marrow biopsies of patients with ET, PV, PMF and chronic myelogenous leukaemia (CML) were immunostained to heparanase, TF and TF pathway inhibitor (TFPI). Erythropoietin receptor positive cell lines U87 human glioma and MCF-7 human breast carcinoma were studied. Heparanase and TFPI staining were more prominent in ET, PV and PMF compared to CML. The strongest staining was in JAK-2 positive ET biopsies. Heparanase level and procoagulant activity were higher in U87 cells transfected to over express JAK-2 V617F mutation compared to control and the effect was reversed using JAK-2 inhibitors (Ruxolitinib, VZ3) and hydroxyurea, although the latter drug did not inhibit JAK-2 phosphorylation. Erythropoietin increased while JAK-2 inhibitors decreased the heparanase level and procoagulant activity in U87 and MCF-7 parental cells. In conclusion, JAK-2 is involved in heparanase up-regulation via the erythropoietin receptor. The present findings may potentially point to a new mechanism of thrombosis in JAK-2 positive ET patients. PMID:26489695

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

    PubMed

    Cummings, Cynthia L; Connelly, Linda K

    2016-01-01

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

  18. Interactions Increase Forager Availability and Activity in Harvester Ants

    PubMed Central

    Pinter-Wollman, Noa; Crow, Sam; Allen, Kelsey; Mathur, Maya B.; Gordon, Deborah M.

    2015-01-01

    Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated. PMID:26539724

  19. Interactions Increase Forager Availability and Activity in Harvester Ants.

    PubMed

    Pless, Evlyn; Queirolo, Jovel; Pinter-Wollman, Noa; Crow, Sam; Allen, Kelsey; Mathur, Maya B; Gordon, Deborah M

    2015-01-01

    Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated. PMID:26539724

  20. 5-Lipoxygenase Activity Increases Susceptibility to Experimental Paracoccidioides brasiliensis Infection

    PubMed Central

    Tristão, Fabrine Sales Massafera; Rocha, Fernanda Agostini; Moreira, Ana Paula; Cunha, Fernando Queiroz; Rossi, Marcos Antonio

    2013-01-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the thermodimorphic fungus Paracoccidioides brasiliensis. Leukotrienes and lipoxins are lipid mediators produced after 5-lipoxygenase (5-LO) activation that exhibit pro- and anti-inflammatory roles, respectively. Here, we have investigated the contribution of 5-LO enzymatic activity in PCM using an experimental model of P. brasiliensis infection. B6.129 wild-type (B6.129) and 5-LO-deficient (5-LO−/−) mice were intravenously inoculated with a virulent strain of P. brasiliensis (Pb18), and the survival rate of the infected mice was investigated on different days after yeast infection. 5-LO−/− mice exhibited an increased survival rate associated with a decreased number of CFU. The resistance of 5-LO−/− during PCM was associated with augmented nitric oxide (NO) production and the formation of compact granulomas. In addition, the absence of 5-LO was associated with a diminished number of CD4+ CD25+ regulatory T cells, higher levels of gamma interferon and interleukin-12, and increased T-bet (a T-box transcription factor that directs Th1 lineage commitment) mRNA levels in the lungs. Taken together, our results show for the first time that 5-LO enzymatic activity increases susceptibility to P. brasiliensis, suggesting that this pathway may be a potential target for therapeutic intervention during PCM. PMID:23381993

  1. Projecting climate-driven increases in North American fire activity

    NASA Astrophysics Data System (ADS)

    Wang, D.; Morton, D. C.; Collatz, G. J.

    2013-12-01

    Climate regulates fire activity through controls on vegetation productivity (fuels), lightning ignitions, and conditions governing fire spread. In many regions of the world, human management also influences the timing, duration, and extent of fire activity. These coupled interactions between human and natural systems make fire a complex component of the Earth system. Satellite data provide valuable information on the spatial and temporal dynamics of recent fire activity, as active fires, burned area, and land cover information can be combined to separate wildfires from intentional burning for agriculture and forestry. Here, we combined satellite-derived burned area data with land cover and climate data to assess fire-climate relationships in North America between 2000-2012. We used the latest versions of the Global Fire Emissions Database (GFED) burned area product and Modern-Era Retrospective Analysis for Research and Applications (MERRA) climate data to develop regional relationships between burned area and potential evaporation (PE), an integrated dryness metric. Logistic regression models were developed to link burned area with PE and individual climate variables during and preceding the fire season, and optimal models were selected based on Akaike Information Criterion (AIC). Overall, our model explained 85% of the variance in burned area since 2000 across North America. Fire-climate relationships from the era of satellite observations provide a blueprint for potential changes in fire activity under scenarios of climate change. We used that blueprint to evaluate potential changes in fire activity over the next 50 years based on twenty models from the Coupled Model Intercomparison Project Phase 5 (CMIP5). All models suggest an increase of PE under low and high emissions scenarios (Representative Concentration Pathways (RCP) 4.5 and 8.5, respectively), with largest increases in projected burned area across the western US and central Canada. Overall, near

  2. Changes in baseball batters' brain activity with increased pitch choice.

    PubMed

    Ryu, Kwangmin; Kim, Jingu; Ali, Asif; Kim, Woojong; Radlo, Steven J

    2015-09-01

    In baseball, one factor necessary for batters to decide whether to swing or not depends on what type of pitch is thrown. Oftentimes batters will look for their pitch (i.e., waiting for a fastball). In general, when a pitcher has many types of pitches in his arsenal, batters will have greater difficulty deciding upon the pitch thrown. Little research has been investigated the psychophysiology of a batters decision-making processes. Therefore, the primary purpose of this study was to determine how brain activation changes according to an increase in the number of alternatives (NA) available. A total of 15 male college baseball players participated in this study. The stimuli used in this experiment were video clips of a right-handed pitcher throwing fastball, curve, and slider pitches. The task was to press a button after selecting the fastball as the target stimulus from two pitch choices (fastball and curve), and then from three possibilities (fastball, curve, and slider). Functional and anatomic image scanning magnetic resonance imaging (MRI) runs took 4 and 5[Formula: see text]min, respectively. According to our analysis, the right precentral gyrus, left medial frontal gyrus, and right fusiform gyrus were activated when the NA was one. The supplementary motor areas (SMA) and primary motor cortex were activated when there were two alternatives to choose from and the inferior orbitofrontal gyrus was specifically activated with three alternatives. Contrary to our expectations, the NA was not a critical factor influencing the activation of related decision making areas when the NA was compared against one another. These findings highlight that specific brain areas related to decision making were activated as the NA increased. PMID:26227537

  3. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    PubMed

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

  4. Increasing Children's Physical Activity During the School Day.

    PubMed

    Hatfield, Daniel Philip; Chomitz, Virginia Rall

    2015-06-01

    Insufficient levels of daily physical activity (PA) among children in the USA and worldwide have profound implications for pediatric obesity and children's health and well-being more generally. Public health recommendations highlight the central role that schools play in providing equitable opportunities for PA for all children. This review identifies evidence-based approaches for increasing children's PA throughout the school day and discusses multilevel factors that support implementation of such approaches. Opportunities to increase school-day PA span not only in-school time (e.g., quality recess and physical education, classroom activity breaks) but also time before school (e.g., active commuting initiatives) and after school (e.g., intramural and interscholastic sports programs). For such approaches to impact children's PA, dimensions of implementation such as adoption, fidelity, penetration, implementation costs, and sustainability are critical. Multilevel factors that influence implementation include policies, school environment and organizational factors, teacher and classroom factors, child and family characteristics, and attributes of the PA approach itself. Research and field observations reinforce the importance of understanding challenges specific to working with schools, including multiple stakeholders, competing priorities, limited facilities and staff capacity, and heterogeneity of students. Thus, while schools hold promise as promoters and equalizers of PA engagement for all children, more research is needed on the levers that influence implementation of effective school-based PA policies and programs. PMID:26627212

  5. Betaine increases the butyrylcholinesterase activity in rat plasma.

    PubMed

    Šišková, K; Dubničková, M; Pašková, Ľ; Rajdl, D; Ďuračková, Z; Muchová, J; Pauliková, I; Racek, J

    2016-03-14

    The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; p<0.001 and 0.41+/-0.11 (B) vs. 0.22+/-0.04 (control) O.D./min/mg; p=0.001). In conclusion, betaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account. PMID:26596326

  6. Obstruction increases activation in the right inferior frontal gyrus.

    PubMed

    Liu, Tao; Saito, Hirofumi; Oi, Misato

    2016-08-01

    The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions. PMID:26366676

  7. Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition

    PubMed Central

    Bernik, Maria B.

    1973-01-01

    Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways—affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis. PMID:4266421

  8. Both novelty and expertise increase action observation network activity

    PubMed Central

    Liew, Sook-Lei; Sheng, Tong; Margetis, John L.; Aziz-Zadeh, Lisa

    2013-01-01

    Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON), is modulated by one's expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal) on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices), 11 experienced occupational therapists (OTs) who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ), as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing—similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ) and extreme novelty (novices) can result in the greatest AON activity. PMID:24062656

  9. Building a Better Mousetrap (Exergame) to Increase Youth Physical Activity.

    PubMed

    Baranowski, Tom; Maddison, Ralph; Maloney, Ann; Medina, Ernie; Simons, Monique

    2014-04-01

    Although exergames have been demonstrated to induce moderate levels of physical activity (PA) if played as designed, there is conflicting evidence on use of exergaming leading to increased habitual PA. Exergames have increased PA in some home and school studies, but not others. Exergames have been used in community centers to good effect, but this has not generally been validated with research. PA from exergames may be enhanced by innovative use of sensors, "fun"-enhancing procedures, tailored messaging, message framing, story or narrative, goal setting, feedback, and values-based messaging. Research is needed on PA-enhancing procedures used within exergames for youth to provide a firmer foundation for the design and use of exergames in the future. PMID:26196047

  10. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  11. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    PubMed Central

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  12. Prescribed Active Learning Increases Performance in Introductory Biology

    PubMed Central

    O'Connor, Eileen; Parks, John W.; Cunningham, Matthew; Hurley, David; Haak, David; Dirks, Clarissa; Wenderoth, Mary Pat

    2007-01-01

    We tested five course designs that varied in the structure of daily and weekly active-learning exercises in an attempt to lower the traditionally high failure rate in a gateway course for biology majors. Students were given daily multiple-choice questions and answered with electronic response devices (clickers) or cards. Card responses were ungraded; clicker responses were graded for right/wrong answers or participation. Weekly practice exams were done as an individual or as part of a study group. Compared with previous versions of the same course taught by the same instructor, students in the new course designs performed better: There were significantly lower failure rates, higher total exam points, and higher scores on an identical midterm. Attendance was higher in the clicker versus cards section; attendance and course grade were positively correlated. Students did better on clicker questions if they were graded for right/wrong answers versus participation, although this improvement did not translate into increased scores on exams. In this course, achievement increases when students get regular practice via prescribed (graded) active-learning exercises. PMID:17548875

  13. Obesity-induced increases in sympathetic nerve activity: sex matters

    PubMed Central

    Brooks, Virginia L.; Shi, Zhigang; Holwerda, Seth W.; Fadel, Paul J.

    2016-01-01

    Abundant evidence obtained largely from male human and animal subjects indicates that obesity increases sympathetic nerve activity (SNA), which contributes to hypertension development. However, recent studies that included women reported that the strong relationships between muscle SNA and waist circumference or body mass index (BMI) found in men are not present in overweight and obese women. A similar sex difference in the association between adiposity and hypertension development has been identified in animal models of obesity. In this brief review, we consider two possible mechanisms for this sex difference. First, visceral adiposity, leptin, insulin, and angiotensin II have been identified as potential culprits in obesity-induced sympathoexcitation in males. We explore if these factors wield the same impact in females. Second, we consider if sex differences in vascular reactivity to sympathetic activation contribute. Our survey of the literature suggests that premenopausal females may be able to resist obesity-induced sympathoexcitation and hypertension in part due to differences in adipose disposition as well as its muted inflammatory response and reduced production of pressor versus depressor components of the renin-angiotensin system. In addition, vascular responsiveness to increased SNA may be reduced. However, more importantly, we identify the urgent need for further study, not only of sex differences per se, but also of the mechanisms that may mediate these differences. This information is required not only to refine treatment options for obese premenopausal women but also to potentially reveal new therapeutic avenues in obese men and women. PMID:25435000

  14. Effect of increasing the choice of active options on children’s physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To determine whether increasing the choice of physical activity options increases the duration and intensity of children’s physical activity. Design: This cross-sectional laboratory study included gender (male, female) and choice group [single toy (no choice), three toys (low choice...

  15. Geometric complexity is increased in in vitro activated platelets.

    PubMed

    Bianciardi, Giorgio

    2015-06-01

    This article investigates the use of computerized fractal analysis for objective characterization of the complexity of platelets in vitro stimulated by low level thrombin (0.02 U mL(-1) ), collected from healthy individuals and observed by means of transmission electron microscopy. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension was evaluated by the box-counting technique (measure of geometric complexity of the platelet outline). The results showed that the platelet boundary is fractal when observed by transmission electron microscopy and that, after an in vitro platelet activation test, the shape of platelets present increased geometric complexity in comparison to the no stimulated platelets (P < 0.001), with 100% correct classification. Computerized fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation. The results may play important roles in the evaluation of the platelets status in pathological conditions, like as atherosclerosis and diabetes mellitus, where in in vivo activated platelets have been described. PMID:25808036

  16. The October-November, 2003 Solar Activity and its Relationship to the "approximately 155 day" Solar Periodicity

    NASA Technical Reports Server (NTRS)

    Richardson, I. G.; Cane, H. V.

    2005-01-01

    Periodicities of - 155 days in various solar and interplanetary phenomena were first discovered during solar cycle 21 and have been shown t o be intermittently present in other solar cycles. In the current solar cycle (23), they have been reported in solar energetic particle events and interplanetary coronal maSS ejections. We assess whether the "unexpected" October - November 2003 burst of solar activity during the late declining phase of the cycle may have been a manifestation of such a periodic behavior, and hence might have been to =me extent "predictable". If the pattern were to continue, episodes of enhanced activity might be expected around April - May and October, 2004. There was a mod- est increase activity increase in mid-April, 2004 which may conform to this pattern.

  17. Involving Community Stakeholders to Increase Park Use and Physical Activity

    PubMed Central

    Marsh, Terry; Mariscal, Mark; Pina-Cortez, Sophia; Cohen, Deborah A.

    2014-01-01

    Objective To describe implementation of a randomized controlled trial of community-based participatory research (CBPR) approaches to increase park use and physical activity across 33 diverse neighborhoods in Los Angeles. Methods Fifty parks were randomly assigned based on park size, facilities and programs, and neighborhood socio-demographic characteristics to: park director (PD, 17 parks); PD and park advisory board of interested community members (PD+PAB, 16 parks); and no-intervention control (17 parks) arms. Between 2007 and 2012, PDs and PABs from the 33 intervention parks participated in community engagement, baseline assessment, marketing training, intervention design and implementation, and follow-up assessment. Results Intervention parks (PD and PD+PAB) invested in new and diversified signage, promotional items, outreach or support for group activities like fitness classes and walking clubs, and various marketing strategies. Scaling up CBPR methods across parks in 33 diverse neighborhoods was challenging. Working with departmental management and established structures for community input (PABs) and park policy (PDs) facilitated implementation and sustainability. Conclusion Scaling up CBPR methods across diverse communities involved tradeoffs. CBPR is useful for tailoring research and enhancing community impact and sustainability, but more work is needed to understand how to conduct multi-site trials across diverse settings using CBPR. PMID:24674853

  18. L-tyrosine administration increases acetylcholinesterase activity in rats.

    PubMed

    Ferreira, Gabriela K; Carvalho-Silva, Milena; Gonçalves, Cinara L; Vieira, Júlia S; Scaini, Giselli; Ghedim, Fernando V; Deroza, Pedro F; Zugno, Alexandra I; Pereira, Talita C B; Oliveira, Giovanna M T; Kist, Luiza W; Bogo, Maurício R; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2012-12-01

    Tyrosinemia is a rare genetic disease caused by mutations on genes that codify enzymes responsible for tyrosine metabolism. Considering that tyrosinemics patients usually present symptoms associated with central nervous system alterations that ranges from slight decreases in intelligence to severe mental retardation, we decided to investigate whether acute and chronic administration of L-tyrosine in rats would affect acetylcholinesterase mRNA expression and enzymatic activity during their development. In our acute protocol, Wistar rats (10 and 30 days old) were killed one hour after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old) and rats were killed 12 h after last injection. Acetylcholinesterase activity was measured by Ellman's method and acetylcholinesterase expression was carried out by a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay. We observed that acute (10 and 30 days old rats) and chronic L-tyrosine administration increased acetylcholinesterase activity in serum and all tested brain areas (hippocampus, striatum and cerebral cortex) when compared to control group. Moreover, there was a significant decrease in mRNA levels of acetylcholinesterase in hippocampus was observed after acute protocol (10 and 30 days old rats) and in striatum after chronic protocol. In case these alterations also occur in the brain of the patients, our results may explain, at least in part, the neurological sequelae associated with high plasma concentrations of tyrosine seen in patients affected by tyrosinemia type II. PMID:23046746

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

    PubMed

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

    2014-10-01

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

  20. Increased oscillatory theta activation evoked by violent digital game events.

    PubMed

    Salminen, Mikko; Ravaja, Niklas

    2008-04-11

    The authors examined electroencephalographic (EEG) oscillatory responses to two violent events, the player character wounding and killing an opponent character with a gun, in the digital game James Bond 007: NightFire. EEG was recorded from 25 (16 male) right-handed healthy young adults. EEG data were segmented into one 1-s baseline epoch before each event and two 1-s epochs after event onset. Power estimates (microV(2)) were derived with the fast Fourier transform (FFT) for each artefact free event. Both of the studied events evoked increased occipital theta (4-6Hz) responses as compared to the pre-event baseline. The wounding event evoked also increased occipital high theta (6-8Hz) response and the killing event evoked low alpha (8-10Hz) asymmetry over the central electrodes, both relative to the pre-event baseline. The results are discussed in light of facial electromyographic and electrodermal activity responses evoked by these same events, and it is suggested that the reported EEG responses may be attributable to affective processes related to these violent game events. PMID:18325669

  1. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils. PMID:25172460

  2. Immobilization induces a very rapid increase in osteoclast activity

    NASA Astrophysics Data System (ADS)

    Heer, Martina; Baecker, Natalie; Mika, Claudia; Boese, Andrea; Gerzer, Rupert

    2005-07-01

    We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6° head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results—pronounced rise of bone resorption markers—that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.

  3. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    SciTech Connect

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  4. Chronic electrical stimulation homeostatically decreases spontaneous activity, but paradoxically increases evoked network activity

    PubMed Central

    Goel, Anubhuti

    2013-01-01

    Neural dynamics generated within cortical networks play a fundamental role in brain function. However, the learning rules that allow recurrent networks to generate functional dynamic regimes, and the degree to which these regimes are themselves plastic, are not known. In this study we examined plasticity of network dynamics in cortical organotypic slices in response to chronic changes in activity. Studies have typically manipulated network activity pharmacologically; we used chronic electrical stimulation to increase activity in in vitro cortical circuits in a more physiological manner. Slices were stimulated with “implanted” electrodes for 4 days. Chronic electrical stimulation or treatment with bicuculline decreased spontaneous activity as predicted by homeostatic learning rules. Paradoxically, however, whereas bicuculline decreased evoked network activity, chronic stimulation actually increased the likelihood that evoked stimulation elicited polysynaptic activity, despite a decrease in evoked monosynaptic strength. Furthermore, there was an inverse correlation between spontaneous and evoked activity, suggesting a homeostatic tradeoff between spontaneous and evoked activity. Within-slice experiments revealed that cells close to the stimulated electrode exhibited more evoked polysynaptic activity and less spontaneous activity than cells close to a control electrode. Collectively, our results establish that chronic stimulation changes the dynamic regimes of networks. In vitro studies of homeostatic plasticity typically lack any external input, and thus neurons must rely on “spontaneous” activity to reach homeostatic “set points.” However, in the presence of external input we propose that homeostatic learning rules seem to shift networks from spontaneous to evoked regimes. PMID:23324317

  5. Altered behaviour in spotted hyenas associated with increased human activity

    USGS Publications Warehouse

    Boydston, E.E.; Kapheim, K.M.; Watts, H.E.; Szykman, M.; Holekamp, K.E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996-98 with that observed several years earlier and found many differences. Female hyenas in 1996-98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988-90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988-90. Finally, hyenas occurred in smaller groups in 1996-98 than in 1988-90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction. ?? 2003 The Zoological Society of London.

  6. Nest predation increases with parental activity: Separating nest site and parental activity effects

    USGS Publications Warehouse

    Martin, T.E.; Scott, J.; Menge, C.

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators have found similar results. We tested whether nest site effects might yield higher predation during incubation because the most obvious sites are depredated most rapidly. We conducted experiments using nest sites from the previous year to remove parental activity. Our results showed that nest sites have highly repeatable effects on nest predation risk; poor nest sites incurred rapid predation and caused predation rates to be greater during the incubation than nestling stage. This pattern also was exhibited in a bird species with similar (i.e. controlled) parental activity between nesting stages. Once nest site effects are taken into account, nest predation shows a strong proximate increase with parental activity during the nestling stage within and across species. Parental activity and nest sites exert antagonistic influences on current estimates of nest predation between nesting stages and both must be considered in order to understand current patterns of nest predation, which is an important source of natural selection.

  7. Nest predation increases with parental activity: separating nest site and parental activity effects.

    PubMed Central

    Martin, T E; Scott, J; Menge, C

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators have found similar results. We tested whether nest site effects might yield higher predation during incubation because the most obvious sites are depredated most rapidly. We conducted experiments using nest sites from the previous year to remove parental activity. Our results showed that nest sites have highly repeatable effects on nest predation risk; poor nest sites incurred rapid predation and caused predation rates to be greater during the incubation than nestling stage. This pattern also was exhibited in a bird species with similar (i.e. controlled) parental activity between nesting stages. Once nest site effects are taken into account, nest predation shows a strong proximate increase with parental activity during the nestling stage within and across species. Parental activity and nest sites exert antagonistic influences on current estimates of nest predation between nesting stages and both must be considered in order to understand current patterns of nest predation, which is an important source of natural selection. PMID:11413645

  8. Engaging parents to increase youth physical activity: A systematic review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parents are often involved in interventions to engage youth in physical activity, but it is not clear which methods for involving parents are effective. A systematic review was conducted of interventions with physical activity and parental components among healthy youth to identify how best to invol...

  9. Opportunities for public health to increase physical activity among youths.

    PubMed

    Piercy, Katrina L; Dorn, Joan M; Fulton, Janet E; Janz, Kathleen F; Lee, Sarah M; McKinnon, Robin A; Pate, Russell R; Pfeiffer, Karin A; Young, Deborah Rohm; Troiano, Richard P; Lavizzo-Mourey, Risa

    2015-03-01

    Despite the well-known benefits of youths engaging in 60 or more minutes of daily physical activity, physical inactivity remains a significant public health concern. The 2008 Physical Activity Guidelines for Americans (PAG) provides recommendations on the amount of physical activity needed for overall health; the PAG Midcourse Report (2013) describes effective strategies to help youths meet these recommendations. Public health professionals can be dynamic change agents where youths live, learn, and play by changing environments and policies to empower youths to develop regular physical activity habits to maintain throughout life. We have summarized key findings from the PAG Midcourse Report and outlined actions that public health professionals can take to ensure that all youths regularly engage in health-enhancing physical activity. PMID:25602864

  10. Postural Cueing to Increase Lumbar Lordosis Increases Lumbar Multifidus Activation During Trunk Stabilization Exercises: Electromyographic Assessment Using Intramuscular Electrodes.

    PubMed

    Beneck, George J; Story, John W; Donald, Shelby

    2016-04-01

    Study Design Controlled laboratory study, repeated-measures design. Background Diminished multifidus activation and cross-sectional area are frequent findings in persons with low back pain. Increasing lumbar lordosis has been shown to increase activation of the multifidus with a minimal increase in activation of the long global extensors during unsupported sitting. Objectives To examine the influence of postural cueing to increase lumbar lordosis on lumbar extensor activation during trunk stabilization exercises. Methods Thirteen asymptomatic participants (9 male, 4 female) were instructed to perform 6 trunk stabilization exercises using a neutral position and increasing lumbar lordosis. Electrical activity of the deep multifidus and longissimus thoracis was recorded using fine-wire intramuscular electrodes. The mean root-mean-square of the electromyography (EMG) signal obtained during each exercise was normalized to a maximum voluntary isometric contraction (MVIC). A 2-way, repeated-measures analysis of variance (posture by exercise) was performed for each muscle. Results When averaged across the 6 exercises, postural cueing to increase lumbar lordosis resulted in greater multifidus EMG activity compared to performing the exercises in a neutral posture (35.3% ± 15.1% versus 29.5% ± 11.2% MVIC). No significant increase in longissimus thoracis EMG activity was observed when exercising with cueing to increase lumbar lordosis. Conclusion This study suggests that postural cueing to increase lumbar lordosis during trunk stabilization exercises may better promote multifidus activation than traditional stabilization exercises alone. Future studies are needed to determine whether increasing lumbar lordosis improves multifidus activation in persons with low back pain. J Orthop Sports Phys Ther 2016;46(4):293-299. Epub 8 Mar 2016. doi:10.2519/jospt.2016.6174. PMID:26954268

  11. Increasing Physical Activity in Children: From Evidence to Action.

    PubMed

    Jakubowski, Tami L; Faigenbaum, Avery D; Lindberg, Claire

    2015-01-01

    Daily physical activity has the potential to improve health and well-being, yet worldwide surveillance of physical activity levels indicate a growing number of children and adolescents do not meet current physical activity recommendations. The current symptom-reactive paradigm should be reconsidered, and preventive actions initiated, before inactive children become resistant to targeted interventions and require pharmacotherapy, and expensive medical procedures for treatment of preventable illnesses. A cascade of adverse events are associated with a sedentary lifestyle. Nurses are uniquely qualified to identify youth with exercise deficits and encourage daily participation in a variety of age-related physical activities that enhance both health- and skill-related components of physical fitness.Physical activity guidelines should support evidence-based activity recommendations by nurses working with children. New insights regarding the importance of improving muscular strength and motor skill performance early in life are valuable to nurses in formulating exercise recommendations for school-age youth. Specific education in pediatric exercise science provides the foundation for prescribing age-related exercise interventions consistent with the needs, abilities, and interests of infants, toddlers, children, and adolescents. Given the critical importance of primary prevention, transformational change in the current system for identifying and treating youth with exercise deficits is warranted. PMID:25811394

  12. Conjugation of type I antifreeze protein to polyallylamine increases thermal hysteresis activity.

    PubMed

    Can, Ozge; Holland, Nolan B

    2011-10-19

    Antifreeze proteins (AFPs) are ice binding proteins found in some plants, insects, and Antarctic fish allowing them to survive at subzero temperatures by inhibiting ice crystal growth. The interaction of AFPs with ice crystals results in a difference between the freezing and melting temperatures, termed thermal hysteresis, which is the most common measure of AFP activity. Creating antifreeze protein constructs that reduce the concentration of protein needed to observe thermal hysteresis activities would be beneficial for diverse applications including cold storage of cells or tissues, ice slurries used in refrigeration systems, and food storage. We demonstrate that conjugating multiple type I AFPs to a polyallylamine chain increases thermal hysteresis activity compared to the original protein. The reaction product is approximately twice as active when compared to the same concentration of free proteins, yielding 0.5 °C thermal hysteresis activity at 0.3 mM protein concentration. More impressively, the amount of protein required to achieve a thermal hysteresis of 0.3 °C is about 100 times lower when conjugated to the polymer (3 μM) compared to free protein (300 μM). Ice crystal morphologies observed in the presence of the reaction product are comparable to those of the protein used in the conjugation reaction. PMID:21905742

  13. China's Changbaishan volcano showing signs of increased activity

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-10-01

    Roughly 1100 years ago, the Changbaishan volcano that lies along the border between northeastern China and North Korea erupted, sending pyroclastic flows dozens of kilometers and blasting a 5-kilometer-wide chunk off of the tip of the stratovolcano. The eruption, known as the Millennium eruption because of its proximity to the turn of the first millennium, was one of the largest volcanic events in the Common Era. In the subsequent period, there have been three smaller eruptions, the most recent of which took place in 1903. Starting in 1999, spurred by signs of resumed activity, scientists established the Changbaishan Volcano Observatory, a network to track changing gas compositions, seismic activity, and ground deformation. Reporting on the data collected over the past 12 years, Xu et al. found that these volcanic indices each leapt during a period of heightened activity from 2002 to 2006.

  14. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    PubMed

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes. PMID:26033609

  15. Somatosensory Anticipatory Alpha Activity Increases to Suppress Distracting Input

    ERIC Educational Resources Information Center

    Haegens, Saskia; Luther, Lisa; Jensen, Ole

    2012-01-01

    Effective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top-down modulation of oscillatory alpha band activity (8-14 Hz) serves to allocate resources to various regions, depending on task…

  16. Texting to increase physical activity in teens: Development & preliminary

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our purpose was to present formative research and preliminary results for a self-determination-theory (SDT)-based text messages to promote physical activity (PA) among teens. Thirty 14- to 17-year olds, stratified by gender and race/ethnicity (Black, Hispanic, White), were recruited to participate i...

  17. Increasing Pupil Physical Activity: A Comprehensive Professional Development Effort

    ERIC Educational Resources Information Center

    Kulinna, Pamela Hodges

    2012-01-01

    Study aim: To determine if pupil physical activity and Body Mass Index classifications maintained or improved after a one-year professional development program involving both classroom and physical education teachers. Guskey's model of teacher change guided this study. Material and methods: Indigenous children from ten schools (N = 320) in grades…

  18. VERB [TM] Summer Scorecard: Increasing Tween Girls' Vigorous Physical Activity

    ERIC Educational Resources Information Center

    Alfonso, Moya L.; Thompson, Zachary; McDermott, Robert J.; Colquitt, Gavin; Jones, Jeffery A.; Bryant, Carol A.; Courtney, Anita H.; Davis, Jenna L.; Zhu, Yiliang

    2013-01-01

    Objective: We assessed changes in the frequency of self-reported physical activity (PA) among tween girls exposed and not exposed to the VERB [TM] Summer Scorecard (VSS) intervention in Lexington, Kentucky, during 2004, 2006, and 2007. Methods: Girls who reported 0-1 day per week of PA were classi?ed as having "little or no" PA. Girls who reported…

  19. Increasing Physical Activity of Children during School Recess

    ERIC Educational Resources Information Center

    Hayes, Lynda B.; Van Camp, Carole M.

    2015-01-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M?=?1,956 steps) were 47% higher than in baseline (M?=?1,326 steps), and the…

  20. Soil disturbance increases soil microbial enzymatic activity in arid ecoregion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional diversity of the soil microbial community is commonly used in the assessment of soil health as it relates to the activity of soil microflora involved in carbon cycling. Soil microbes in different microenvironments will have varying responses to different substrates, thus catabolic fingerp...

  1. Walking Associated With Public Transit: Moving Toward Increased Physical Activity in the United States

    PubMed Central

    Banerjee, Shailendra N.; Dannenberg, Andrew L.; Wendel, Arthur M.

    2013-01-01

    Objectives. We assessed changes in transit-associated walking in the United States from 2001 to 2009 and documented their importance to public health. Methods. We examined transit walk times using the National Household Travel Survey, a telephone survey administered by the US Department of Transportation to examine travel behavior in the United States. Results. People are more likely to transit walk if they are from lower income households, are non-White, and live in large urban areas with access to rail systems. Transit walkers in large urban areas with a rail system were 72% more likely to transit walk 30 minutes or more per day than were those without a rail system. From 2001 to 2009, the estimated number of transit walkers rose from 7.5 million to 9.6 million (a 28% increase); those whose transit-associated walking time was 30 minutes or more increased from approximately 2.6 million to 3.4 million (a 31% increase). Conclusions. Transit walking contributes to meeting physical activity recommendations. Study results may contribute to transportation-related health impact assessment studies evaluating the impact of proposed transit systems on physical activity, potentially influencing transportation planning decisions. PMID:23327281

  2. T Lymphocyte Activation Threshold is Increased in Reduced Gravity

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  3. Increased physical activity has a greater effect than reduced energy intake on lifestyle modification-induced increases in testosterone.

    PubMed

    Kumagai, Hiroshi; Zempo-Miyaki, Asako; Yoshikawa, Toru; Tsujimoto, Takehiko; Tanaka, Kiyoji; Maeda, Seiji

    2016-01-01

    Obesity has reached epidemic proportions worldwide. Obesity results in reduced serum testosterone levels, which causes many disorders in men. Lifestyle modifications (increased physical activity and calorie restriction) can increase serum testosterone levels. However, it is unknown whether increased physical activity or calorie restriction during lifestyle modifications has a greater effects on serum testosterone levels. Forty-one overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and calorie restriction). We measured serum testosterone levels, the number of steps, and the total energy intake. We divided participants into two groups based on the median change in the number of steps (high or low physical activities) or that in calorie restriction (high or low calorie restrictions). After the program, serum testosterone levels were significantly increased. Serum testosterone levels in the high physical activity group were significantly higher than those in the low activity group. This effect was not observed between the groups based on calorie restriction levels. We found a significant positive correlation between the changes in serum testosterone levels and the number of steps. Our results suggested that an increase in physical activity greatly affected the increased serum testosterone levels in overweight and obese men during lifestyle modification. PMID:26798202

  4. Proteolytic activity of Oenococcus oeni enables the increase in antioxidant and antihypertensive activities from wine.

    PubMed

    Apud, Gisselle Raquel; Stivala, María Gilda; Fernández, Pedro Aredes; Rodríguez Vaquero, María José

    2013-01-01

    Oenococcus oeni is a lactic acid bacterium involved in winemaking where it generally carries out the malolactic fermentation converting the wine's malic acid into lactic acid. In this work were used the strain m of Oenococcus oeni. The culture was inoculated at 10⁸ Log CFU/mL in a synthetic wine medium (SW) supplemented with a fraction of high molecular weight constituted by proteins and polypeptides (FPP) obtained from Cabernet Sauvignon and Syrah wines from Colalao del Valle, Tucumán, Argentine. In presence of FPP, O. oeni maintains viability after 48 h incubation time and release an extracellular proteolytic activity. Therefore, a release peptides of 1.247 and 1.373 mg N/L at 48 h of incubation time was detected in SW supplemented with FPP from Cabernet Sauvignon and Syrah wines respectively. Concomitantly with the maximum peptide release, the "in vitro" biological activities were increased. The released peptides from Cabernet Sauvignon wine enables the increase in the ferric reducing antioxidant power (FRAP) capacity, the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), and the inhibition of angiotensin I-converting enzyme (ACEI activity) in 392.8 µmol FeSO₄/L, 9.7% and 63.9%, respectively. In presence of FPP of Syrah wine, the released peptides increases in 156.5 µmol FeSO₄/L, 5.5% and 13.8% the FRAP, DPPH and ACEI activities, respectively. The utilization of Oenococcus oeni m to carry out the malolactic fermentation would contribute to enhance the beneficial biological activities of the final product and provide an additional value to regional wines. PMID:24372266

  5. Temperature increasing trend due to solar activity at Western Saudi

    NASA Astrophysics Data System (ADS)

    Almleaky, Y. M.; Sharaf, M. A.; Basurah, H. M.; Malawi, A. A.; Al-Mostafa, Z. A.

    The Sun influnce on climate has been discussed globaly by many authors and at different latitudes. In this article we will discuss this connection for the Kingdom of Saudi Arabia, which spans a large area, i.e. 16-32 North and 36-50 East. We started our invistigation in this paper by looking into the temperature at the Western coast of the Kingdom, namely Yenbo and Jeddah. In order to find the correlation between temperature and solar variations we employed one of the most relevant solar quentity, i.e. the solar cycle length. From our invistigations we found an increase in the temperature averages reaching up to 1.0 degree Celsius in certain cities since 1970. It is also found that the temperature increase is strongly correlated with the solar Cycle length, reaching up to 0.8 in some sites.

  6. Increasing nurse and midwife engagement in research activity.

    PubMed

    Mitchell, Kay; Baillie, Lesley; Phillips, Natasha

    2015-02-10

    Nurses and midwives should be able to perform, interpret and implement the results of clinical research to improve the quality of patient care. Increasing the research capacity and capability of healthcare professionals requires strong leadership and a strategic approach. This article describes how one NHS trust supports engagement of nurses and midwives in research through the development of a research strategy and a centre for nurse and midwife-led research. PMID:25649601

  7. Density increase due to active feedback in mirror machine

    NASA Astrophysics Data System (ADS)

    Seemann, Omri; Be'Ery, Ilan

    2014-10-01

    Mirror machines are one of the schemes for future fusion systems. Its main drawbacks are the flute instability and being open ended which results in plasma losses. A feedback system is used to stabilize the flute instability in a table top mirror machine with a continuous plasma source and RF heating. Under certain source density and temperature conditions, although the plasma was stabilized, plasma density increase was not measured. After decreasing the source density and increasing the temperature, Plasma density increase was achieved. It is theorized that these results are due to transition of the plasma main loss mechanism from collision dominated to instability dominated. In the former, the main density loss is through diffusion and In the latter, it is through flute instability which drives the plasma to the edge of the vacuum chamber. Future research directions are discussed for a planned machine which should achieve higher temperatures and better diagnostic capabilities. The research will focus on magnetic actuators and passive RF stabilization.

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

    PubMed Central

    Stephens, Janna; Allen, Jerilyn

    2013-01-01

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

  9. Parent-Targeted Mobile Phone Intervention to Increase Physical Activity in Sedentary Children: Randomized Pilot Trial

    PubMed Central

    Marker, Arwen M; Allen, H Raymond; Machtmes, Ryan; Han, Hongmei; Johnson, William D; Schuna Jr, John M; Broyles, Stephanie T; Tudor-Locke, Catrine; Church, Timothy S

    2014-01-01

    Background Low levels of moderate-to-vigorous physical activity are associated with adverse health consequences. Objective The intent of the study was to determine the feasibility and efficacy of a 12-week physical activity promotion program targeting children, which was delivered to parents through mobile phones. Methods Potential participants were recruited through advertisements placed in the newspaper, local hospitals and schools, and an email listserv. Sedentary children aged 6-10 years were randomly assigned to a minimal (MIG) or intensive (IIG) intervention group. Parents in the MIG were given a goal to increase (within 1 month) and maintain their child’s activity at 6000 pedometer steps/day above their baseline levels and to monitor their child’s steps daily. Parents in the IIG were given the same steps/day and monitoring goals, in addition to text messages and articles containing additional behavioral strategies (based on the Social Cognitive Theory) designed to promote their child’s physical activity. The intervention components were delivered via mobile phone. Anthropometrics, body composition, and questionnaires were administered in a clinic. Children wore a New Lifestyles pedometer (NL-1000) each day throughout the intervention and parents were to monitor their child’s step counts daily. Results Out of 59 children who screened for the study, a total of 27 children (mean age 8.7, SD 1.4 years; 56%, 15/27 female; 59%, 16/27 African American) were enrolled and completed the study. Overall, 97.90% (2220/2268; 98.20%, 1072/1092 for MIG; 97.60%, 1148/1176 for IIG) of expected step data were successfully entered by the parent or study coordinator. Parents in the MIG and IIG were sent approximately 7 and 13 text messages per week, respectively, averaged over the course of the study. IIG parents accessed an average of 6.1 (SD 4.4) articles over the course of the intervention and accessed a fewer number of articles in the last month compared to the first

  10. Maternal immune activation increases seizure susceptibility in juvenile rat offspring.

    PubMed

    Yin, Ping; Zhang, Xin-Ting; Li, Jun; Yu, Lin; Wang, Ji-Wen; Lei, Ge-Fei; Sun, Ruo-Peng; Li, Bao-Min

    2015-06-01

    Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia. PMID:25982885

  11. Activation of glucosidase via stress-induced polymerization rapidly increases active pools of abscisic acid.

    PubMed

    Lee, Kwang Hee; Piao, Hai Lan; Kim, Ho-Youn; Choi, Sang Mi; Jiang, Fan; Hartung, Wolfram; Hwang, Ildoo; Kwak, June M; Lee, In-Jung; Hwang, Inhwan

    2006-09-22

    Abscisic acid (ABA) is a phytohormone critical for plant growth, development, and adaptation to various stress conditions. Plants have to adjust ABA levels constantly to respond to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning ABA levels remain elusive. Here we report that AtBG1, a beta-glucosidase, hydrolyzes glucose-conjugated, biologically inactive ABA to produce active ABA. Loss of AtBG1 causes defective stomatal movement, early germination, abiotic stress-sensitive phenotypes, and lower ABA levels, whereas plants with ectopic AtBG1 accumulate higher ABA levels and display enhanced tolerance to abiotic stress. Dehydration rapidly induces polymerization of AtBG1, resulting in a 4-fold increase in enzymatic activity. Furthermore, diurnal increases in ABA levels are attributable to polymerization-mediated AtBG1 activation. We propose that the activation of inactive ABA pools by polymerized AtBG1 is a mechanism by which plants rapidly adjust ABA levels and respond to changing environmental cues. PMID:16990135

  12. Strategies to Increase After-School Program Staff Skills to Promote Healthy Eating and Physical Activity.

    PubMed

    Weaver, R Glenn; Beets, Michael W; Beighle, Aaron; Webster, Collin; Huberty, Jennifer; Moore, Justin B

    2016-01-01

    Standards targeting children's healthy eating and physical activity (HEPA) in after-school programs call for staff to display or refrain from HEPA-promoting or -discouraging behaviors that are linked to children's HEPA. This study evaluated strategies to align staff behaviors with HEPA Standards. Staff at four after-school programs serving approximately 500 children participated in professional development training from January 2012 to May 2013. Site leaders also attended workshops and received technical support during the same time frame. Changes in staff behaviors were evaluated using the System for Observing Staff Promotion of Activity and Nutrition in a pre- (fall 2011) multiple-post (spring 2012, fall 2012, and spring 2013), no-control group study design. A total of 8,949 scans were completed across the four measurement periods. Of the 19 behaviors measured, 14 changed in the appropriate direction. For example, staff engaging in physical activity with children increased from 27% to 40% of scans and staff eating unhealthy foods decreased from 56% to 14% of days. Ongoing training and technical assistance can have a measureable impact on staff behaviors linked to child-level HEPA outcomes. Future research should explore the feasibility of disseminating ongoing trainings to after-school program staff on a large scale. PMID:26055462

  13. Traditional fermentation increases goitrogenic activity in pearl millet.

    PubMed

    Elnour, A; Liedén, S; Bourdoux, P; Eltom, M; Khalid, S A; Hambraeus, L

    1998-01-01

    Epidemiological evidence suggests that millet might play a role in the etiology of endemic goiter. Recently, we showed that a traditional fermentation procedure of two pearl millet (Pennisetum americanum L. Lecke) cultivars grown in Sudan modified their effects on the weight of the thyroid gland and thyroid hormone profile in rats. In the present study, we report that this fermentation procedure reduced the ash contents of millet by about 40% and removed considerable amounts of Mg (>50%), Zn (27-39%) and K (45%). Other minerals (Ca, Fe, Cu) were not affected. Feeding of one fermented cultivar resulted in significant reduction in bone Mg and Zn contents, whereas feeding of the other fermented cultivar resulted in reduction of bone Mg only. Dietary Mg intake and bone Mg contents correlated negatively with serum T3. Groups fed the millet diets had higher serum Se level compared to those fed wheat or casein diets and feeding of fermented millet resulted in a further increase in serum Se level. Thus our data indicate that in rats the enhanced effects of millet on the thyroid induced by fermentation is likely related to removal of minerals from millet and/or chemical transformation of the goitrogens contained in millet. PMID:9895422

  14. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex.

    PubMed

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B H

    2015-10-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this "reversed" size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys. PMID:25480358

  15. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex

    PubMed Central

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B. H.

    2015-01-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this “reversed” size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys. PMID:25480358

  16. Post-cardiac transplant arteriopathy in piglets is associated with fragmentation of elastin and increased activity of a serine elastase.

    PubMed Central

    Oho, S.; Rabinovitch, M.

    1994-01-01

    In experimental piglets after heterotopic heart transplant, we observed an immune/inflammatory response in the coronary arteries with increased expression of interleukin-1 beta and accumulation of fibronectin and smooth muscle cells in the subendothelium (N. Clausell, S. Molossi, M. Rabinovitch, Am J Pathol 1993, 142, 1772-1786). Proteolytic enzymes including elastases regulate cytokine activity and are associated with the development of neointimal proliferation. We now report ultrastructural evidence of elastolytic activity in the donor compared to host coronary arteries judged by a fivefold increase in the breaks in the internal elastic lamina, (P < 0.01) correlating with a 10-fold increase in elastase activity per mg tissue (P < 0.01). The enzyme activity is serine elastase, i.e., inhibited by phenylmethyl sulfonyl fluoride, and elafin but not EDTA. Using a novel strategy that greatly increases the activity extractable from the tissue, we resolved the enzyme on an elastin substrate gel as a protein of approximately 23 kd. Ours is the first report and characterization of increased elastase activity associated with the development of the post-cardiac transplant coronary arteriopathy. The source may be inflammatory or smooth muscle cells, and elastase may play a pathophysiological role in neointimal proliferation by activating cytokines and growth factors and by release of chemotactic peptides. Images Figure 1 Figure 5 PMID:8030749

  17. Monotone Boolean approximation

    SciTech Connect

    Hulme, B.L.

    1982-12-01

    This report presents a theory of approximation of arbitrary Boolean functions by simpler, monotone functions. Monotone increasing functions can be expressed without the use of complements. Nonconstant monotone increasing functions are important in their own right since they model a special class of systems known as coherent systems. It is shown here that when Boolean expressions for noncoherent systems become too large to treat exactly, then monotone approximations are easily defined. The algorithms proposed here not only provide simpler formulas but also produce best possible upper and lower monotone bounds for any Boolean function. This theory has practical application for the analysis of noncoherent fault trees and event tree sequences.

  18. Development of a universal approach to increase physical activity among adolescents: the GoActive intervention

    PubMed Central

    Corder, Kirsten; Schiff, Annie; Kesten, Joanna M; van Sluijs, Esther M F

    2015-01-01

    Objectives To develop a physical activity (PA) promotion intervention for adolescents using a process addressing gaps in the literature while considering participant engagement. We describe the initial development stages; (1) existing evidence, (2) large scale opinion gathering and (3) developmental qualitative work, aiming (A) to gain insight into how to increase PA among the whole of year 9 (13–14 years-old) by identifying elements for intervention inclusion (B) to improve participant engagement and (C) to develop and refine programme design. Methods Relevant systematic reviews and longitudinal analyses of change were examined. An intervention was developed iteratively with older adolescents (17.3±0.5 years) and teachers, using the following process: (1) focus groups with (A) adolescents (n=26) and (B) teachers (n=4); (2) individual interviews (n=5) with inactive and shy adolescents focusing on engagement and programme acceptability. Qualitative data were analysed thematically. Results Limitations of the existing literature include lack of evidence on whole population approaches, limited adolescent involvement in intervention development, and poor participant engagement. Qualitative work suggested six themes which may encourage adolescents to do more PA; choice, novelty, mentorship, competition, rewards and flexibility. Teachers discussed time pressures as a barrier to encouraging adolescent PA and suggested between-class competition as a strategy. GoActive aims to increase PA through increased peer support, self-efficacy, group cohesion, self-esteem and friendship quality, and is implemented in tutor groups using a student-led tiered-leadership system. Conclusions We have followed an evidence-based iterative approach to translate existing evidence into an adolescent PA promotion intervention. Qualitative work with adolescents and teachers supported intervention design and addressed lack of engagement with health promotion programmes within this age group

  19. Playground Designs to Increase Physical Activity Levels during School Recess: A Systematic Review

    ERIC Educational Resources Information Center

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M.

    2014-01-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A…

  20. GW8510 Increases Insulin Expression in Pancreatic Alpha Cells through Activation of p53 Transcriptional Activity

    PubMed Central

    Fomina-Yadlin, Dina; Kubicek, Stefan; Vetere, Amedeo; He, Kaihui Hu; Schreiber, Stuart L.; Wagner, Bridget K.

    2012-01-01

    Background Expression of insulin in terminally differentiated non-beta cell types in the pancreas could be important to treating type-1 diabetes. Previous findings led us to hypothesize involvement of kinase inhibition in induction of insulin expression in pancreatic alpha cells. Methodology/Principal Findings Alpha (αTC1.6) cells and human islets were treated with GW8510 and other small-molecule inhibitors for up to 5 days. Alpha cells were assessed for gene- and protein-expression levels, cell-cycle status, promoter occupancy status by chromatin immunoprecipitation (ChIP), and p53-dependent transcriptional activity. GW8510, a putative CDK2 inhibitor, up-regulated insulin expression in mouse alpha cells and enhanced insulin secretion in dissociated human islets. Gene-expression profiling and gene-set enrichment analysis of GW8510-treated alpha cells suggested up-regulation of the p53 pathway. Accordingly, the compound increased p53 transcriptional activity and expression levels of p53 transcriptional targets. A predicted p53 response element in the promoter region of the mouse Ins2 gene was verified by chromatin immunoprecipitation (ChIP). Further, inhibition of Jun N-terminal kinase (JNK) and p38 kinase activities suppressed insulin induction by GW8510. Conclusions/Significance The induction of Ins2 by GW8510 occurred through p53 in a JNK- and p38-dependent manner. These results implicate p53 activity in modulation of Ins2 expression levels in pancreatic alpha cells, and point to a potential approach toward using small molecules to generate insulin in an alternative cell type. PMID:22242153

  1. The Influence of Increasing Rain and Earthquake Activities on Landslide Slope Stability in Forest Areas

    NASA Astrophysics Data System (ADS)

    Kubota, T.; Aditian, A.

    2014-12-01

    Deriving the analysis of rainfall data in various mountainous locations, increase in rainfall that is deemed to be induced by the global climate change is obvious in Kyushu district, western Japan. On this point of view, its long term impact on the forest slope stability is analyzed with field investigation and numerical simulation such as finite element method (FEM). On the other hand, the influence of earthquake such as cracks on the slope due to seismic vibration was also analyzed with FEM. In this case, the slope stability analysis to obtain the factor of safety "Fs" is conducted. Here, in case of the Fs > 1.0, the slope is stable. In addition, the slope stabilizing effect of the forest mainly due to the roots strength is evaluated on some unstable slopes. Simultaneously, a holistic estimation over landslide groups is conducted by comparing "Fs" on forest slopes with non- forest slopes. Therefore, the following conclusions are obtained: 1) Comparing the Fs without increased rainfall from the previous decade and the one with actual rainfall, the former case is 1.04 ~1.06 times more stable than the latter. 2) On the other hand, the forest slopes are estimated to be up to approximately 1.5 to 2.5 times more stable than the slope without forest. Therefore, the slope stabilizing effect by the forest is much higher than the increasing rainfall influence i.e. the climate change effect. These results imply that an appropriate forest existence is important under the climate change condition to prevent forest slope degradation. 3) Comparing with the destabilization of the slope by seismic activities (vibration) due to the reduction of soil strength and "cracks = slope deformation" (8~9 % to 30% reduction in Fs even after an earthquake of 490gal), the influence of the long term rainfall increase on slopes (such as 1% decrease in Fs) is relatively small in the study area.

  2. Effects of increasing size and changing europium activator concentration in KCaI3 scintillator crystals

    NASA Astrophysics Data System (ADS)

    Lindsey, Adam C.; Zhuravleva, Mariya; Wu, Yuntao; Stand, Luis; Loyd, Matthew; Gokhale, Sasmit; Koschan, Merry; Melcher, Charles L.

    2016-09-01

    KCaI3:Eu crystals have been identified as very promising for use in spectroscopic detector applications related to nuclear nonproliferation and domestic security efforts. Initial studies have shown for small crystals a few mm3 in size with 3% europium dopant concentration, a high light yield of >70,000 ph/MeV and energy resolution of ≈3% at 662 keV is attainable which is comparable with the highest performance scintillators discovered. In this work, single crystals of KCaI3 with a range of Eu2+ doping between 0 and 5 at% substituting for Ca2+ were grown at 22 mm diameter and their performance for gamma-ray spectroscopy studied. Comparisons among crystals approximately Ø22 mm×22 mm (8.4 cm3 or ≈0.5 in3) provide a more accurate understanding of how scintillation performance changes with Eu doping and increased crystal size. KCaI3 in the undoped form is shown to be a highly efficient intrinsic scintillator with a defect-related emission at 404 nm which coexists with the Eu2+ 5d-4f emission in low dopant concentrations and is completely re-absorbed in more heavily doped crystals. For larger crystals, effects from self-absorption due to Eu activation become more evident by a near doubling of decay time for 0.5 in3 crystals as the activator is increased from 0.5 to 5.0 at% Eu. Comparisons of pulse-height spectra obtained for Ø22 mm×22 mm cylinders with varying Eu concentration suggests best performance is achieved using lower Eu additions closer to 0.5-1.0 at%. Using a modified crystal packaging featuring an offset reflector geometry, 0.5 in3 crystals of KCaI3:Eu can attain under 4% energy resolution at 662 keV.

  3. Increased Biomass Yield of Lactococcus lactis by Reduced Overconsumption of Amino Acids and Increased Catalytic Activities of Enzymes

    PubMed Central

    Adamberg, Kaarel; Seiman, Andrus; Vilu, Raivo

    2012-01-01

    Steady state cultivation and multidimensional data analysis (metabolic fluxes, absolute proteome, and transcriptome) are used to identify parameters that control the increase in biomass yield of Lactococcus lactis from 0.10 to 0.12 C-mol C-mol−1 with an increase in specific growth rate by 5 times from 0.1 to 0.5 h−1. Reorganization of amino acid consumption was expressed by the inactivation of the arginine deiminase pathway at a specific growth rate of 0.35 h−1 followed by reduced over-consumption of pyruvate directed amino acids (asparagine, serine, threonine, alanine and cysteine) until almost all consumed amino acids were used only for protein synthesis at maximal specific growth rate. This balanced growth was characterized by a high glycolytic flux carrying up to 87% of the carbon flow and only amino acids that relate to nucleotide synthesis (glutamine, serine and asparagine) were consumed in higher amounts than required for cellular protein synthesis. Changes in the proteome were minor (mainly increase in the translation apparatus). Instead, the apparent catalytic activities of enzymes and ribosomes increased by 3.5 times (0.1 vs 0.5 h−1). The apparent catalytic activities of glycolytic enzymes and ribosomal proteins were seen to follow this regulation pattern while those of enzymes involved in nucleotide metabolism increased more than the specific growth rate (over 5.5 times). Nucleotide synthesis formed the most abundant biomonomer synthetic pathway in the cells with an expenditure of 6% from the total ATP required for biosynthesis. Due to the increase in apparent catalytic activity, ribosome translation was more efficient at higher growth rates as evidenced by a decrease of protein to mRNA ratios. All these effects resulted in a 30% decrease of calculated ATP spilling (0.1 vs 0.5 h−1). Our results show that bioprocesses can be made more efficient (using a balanced metabolism) by varying the growth conditions. PMID:23133574

  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. A CANDELS WFC3 Grism Study of Emission-Line Galaxies at Z approximates 2: A mix of Nuclear Activity and Low-Metallicity Star Formation

    NASA Technical Reports Server (NTRS)

    Trump, Jonathan R.; Weiner, Benjamin J.; Scarlata, Claudia; Kocevski, Dale D.; Bell, Eric F.; McGrath, Elizabeth J.; Koo, David C.; Faber, S. M.; Laird, Elise S.; Mozena, Mark; Rangel, Cyprian; Yan, Renbin; Yesuf, Hassen; Atek, Hakim; Dickinson, Mark; Donley, Jennifer L.; Dunlop, James S.; Ferguson, Henry C.; Finkelstein, Steven L.; Grogin, Norman A.; Hathi, Nimish P.; Juneau, Stephanie; Kartaltepe, Jeyhan S.; Koekemoer, Anton M.; Nandra, Kirpal

    2011-01-01

    We present Hubble Space Telescope Wide Field Camera 3 slitless grism spectroscopy of 28 emission-line galaxies at z approximates 2, in the GOODS-S region of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). The high sensitivity of these grism observations, with > 5-sigma detections of emission lines to f > 2.5 X 10(exp -18( erg/s/ square cm, means that the galaxies in the sample are typically approximately 7 times less massive (median M(star). = 10(exp 9.5)M(solar)) than previously studied z approximates 2 emission-line galaxies. Despite their lower mass, the galaxies have [O-III]/H-Beta ratios which are very similar to previously studied z approximates 2 galaxies and much higher than the typical emission-line ratios of local galaxies. The WFC3 grism allows for unique studies of spatial gradients in emission lines, and we stack the two-dimensional spectra of the galaxies for this purpose. In the stacked data the [O-III] emission line is more spatially concentrated than the H-Beta emission line with 98.1% confidence. We additionally stack the X-ray data (all sources are individually undetected), and find that the average L(sub [O-III])/L(sub 0.5.10keV) ratio is intermediate between typical z approximates 0 obscured active galaxies and star-forming galaxies. Together the compactness of the stacked [O-III] spatial profile and the stacked X-ray data suggest that at least some of these low-mass, low-metallicity galaxies harbor weak active galactic nuclei.

  6. Increasing the Number of Oxygen Vacancies on TiO(2) By Doping With Iron Increases the Activity of Supported Gold for CO Oxidation

    SciTech Connect

    Carrettin, S.; Hao, Y.; Aguilar-Guerrero, V.; Gates, B.C.; Trasobares, S.; Calvino, J.J.; Corma, A.

    2009-05-28

    The addition of iron to high-area TiO{sub 2} (Degussa P25, a mixture of anatase and rutile) increases the number of oxygen defect sites that react with O{sub 2} to form peroxide and superoxide species. In the presence of gold nanoclusters on the TiO{sub 2} surface, the superoxide species become highly reactive, and the activity of the supported gold catalyst for CO oxidation is approximately twice that of the most active comparable catalysts described in the literature. Images of the catalyst obtained by scanning transmission electron microscopy combined with spectra of the catalyst measured in the working state (Raman, extended X-ray absorption fine structure, and X-ray absorption near-edge structure) indicate strong interactions of gold with the support and the presence of iron near the interfaces between the gold clusters and the TiO{sub 2} support. The high activity of the catalysts is attributed to the presence of defects in these sites that activate oxygen.

  7. Increased default mode network activity in socially anxious individuals during reward processing

    PubMed Central

    2014-01-01

    Background Social anxiety has been associated with potentiated negative affect and, more recently, with diminished positive affect. It is unclear how these alterations in negative and positive affect are represented neurally in socially anxious individuals and, further, whether they generalize to non-social stimuli. To explore this, we used a monetary incentive paradigm to explore the association between social anxiety and both the anticipation and consumption of non-social incentives. Eighty-four individuals from a longitudinal community sample underwent functional magnetic resonance imaging (fMRI) while participating in a monetary incentive delay (MID) task. The MID task consisted of alternating cues indicating the potential to win or prevent losing varying amounts of money based on the speed of the participant’s response. We examined whether self-reported levels of social anxiety, averaged across approximately 7 years of data, moderated brain activity when contrasting gain or loss cues with neutral cues during the anticipation and outcome phases of incentive processing. Whole brain analyses and analyses restricted to the ventral striatum for the anticipation phase and the medial prefrontal cortex for the outcome phase were conducted. Results Social anxiety did not associate with differences in hit rates or reaction times when responding to cues. Further, socially anxious individuals did not exhibit decreased ventral striatum activity during anticipation of gains or decreased MPFC activity during the outcome of gain trials, contrary to expectations based on literature indicating blunted positive affect in social anxiety. Instead, social anxiety showed positive associations with extensive regions implicated in default mode network activity (for example, precuneus, posterior cingulate cortex, and parietal lobe) during anticipation and receipt of monetary gain. Social anxiety was further linked with decreased activity in the ventral striatum during anticipation

  8. [Adaptive increase of serotonergic system activity in tissues of half-migratory and migratory fish at increased water salinity].

    PubMed

    2013-01-01

    The article deals with studies of the serotoninergic system activity in different tissues of half-migratory fish--the Caspian roach (Rutilus rutilus caspicus) and carpbream (Abramis brama orientalis)--and migratory fish--shemaya (Chalcalburnus chalcoides) caught in fresh and brackish waters, as well as in the common carp (Cyprinus carpio L.) tissues under effect of brackish water in model experiments. Using indirect solid-phase ELISA-test, the serotoninergic system activity was evaluated by measuring in the tissues of the studied fish the serotonin-modulated anticonsolidation protein (SMAP) which is in linear relationship with serotonin level. There was found a significant elevation of the SMAP levels in the brain of the Caspian roach, carpbream, shemaya, and the common carp under effect of increased water sainity. The revealed increase of the SMAP content in brains of the Caspian roach, carpbream, shemaya, and the common carp under action of increased water salinity reflects the corresponding elevated activity of the serotoninergic system and indicates involvement of adaptive readjustments in the animals' body. PMID:25509051

  9. [Adaptive increase of serotonergic system activity in tissues of half-migratory and migratory fish at increased water salinity].

    PubMed

    Mustafaev, N J; Mekhtiev, A A

    2013-01-01

    The article deals with studies of the serotoninergic system activity in different tissues of half-migratory fish--the Caspian roach (Rutilus rutilus caspicus) and carpbream (Abramis brama orientalis)--and migratory fish--shemaya (Chalcalburnus chalcoides) caught in fresh and brackish waters, as well as in the common carp (Cyprinus carpio L.) tissues under effect of brackish water in model experiments. Using indirect solid-phase ELISA-test, the serotoninergic system activity was evaluated by measuring in the tissues of the studied fish the serotonin-modulated anticonsolidation protein (SMAP) which is in linear relationship with serotonin level. There was found a significant elevation of the SMAP levels in the brain of the Caspian roach, carpbream, shemaya, and the common carp under effect of increased water sainity. The revealed increase of the SMAP content in brains of the Caspian roach, carpbream, shemaya, and the common carp under action of increased water salinity reflects the corresponding elevated activity of the serotoninergic system and indicates involvement of adaptive readjustments in the animals' body. PMID:25490850

  10. Community-based exergaming program increases physical activity and perceived wellness in older adults.

    PubMed

    Strand, Kara A; Francis, Sarah L; Margrett, Jennifer A; Franke, Warren D; Peterson, Marc J

    2014-07-01

    Exergaming may be an effective strategy to increase physical activity participation among rural older adults. This pilot project examined the effects of a 24-wk exergaming and wellness program (8 wk onsite exergaming, 16-wk wellness newsletter intervention) on physical activity participation and subjective health in 46 rural older adults. Sociodemographic data and self-reported physical activity were analyzed using descriptive statistics and Cochran's Q, respectively. Qualitative data were reviewed, categorized on the basis of theme, and tabulated for frequency. Increased physical activity and perceived health were the most reported perceived positive changes. Significant increases in physical activity participation were maintained among participants who were physically inactive at baseline. Best-liked features were physical activity and socialization. Findings suggest that this pilot exergaming and wellness program is effective in increasing physical activity in sedentary rural older adults, increasing socialization, and increasing subjective physical health among rural older adults. PMID:23945726

  11. The effect of increasing autonomy through choice on young children’s physical activity behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing autonomy by manipulating the choice of available physical activity options in a laboratory setting can increase physical activity in older children and adults. However, the effect of manipulating the number of physically active choices has yet to be examined in young children in a gymnas...

  12. Promising School-Based Strategies and Intervention Guidelines to Increase Physical Activity of Adolescents

    ERIC Educational Resources Information Center

    Pardo, Berta Murillo; Bengoechea, Enrique Garcia; Lanaspa, Eduardo Generelo; Bush, Paula L.; Casterad, Javier Zaragoza; Clemente, Jose A. Julian; Gonzalez, Luis Garcia

    2013-01-01

    This narrative review describes the available scientific evidence regarding promising school-based strategies to increase physical activity of adolescents. We conducted a literature search for studies published up to 2011, regarding adolescent physical activity intervention studies that resulted in increased physical activity (regardless of…

  13. An Activity-Based Format Increased Student Retention in a Community College Microbiology Course.

    ERIC Educational Resources Information Center

    Lux, Mary F.

    2002-01-01

    Reports on the modification of a microbiology course to provide the laboratory component at the beginning of the time slot, tailor the lecture topics to relate to the laboratory component each night, and add an outside reading component. Reports that, following this format change, the retention rate increased from approximately 50% to 80%.…

  14. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity.

    PubMed

    Arrol, S; Mackness, M I; Durrington, P N

    2000-05-01

    There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu(2+) was increased by 157% (110-232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185-259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122-192%) (P<0.005) and 177% (101-267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115-169%) (P<0.005) and 171% (122-192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104-153%) (P<0.05) on 200 mg/day and 240% (97-360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12. 7+/-2.6 (mean+/-SEM) to 16+/-3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4+/-2.0 to 19.2+/-3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA

  15. Runx1 Phosphorylation by Src Increases Trans-activation via Augmented Stability, Reduced Histone Deacetylase (HDAC) Binding, and Increased DNA Affinity, and Activated Runx1 Favors Granulopoiesis.

    PubMed

    Leong, Wan Yee; Guo, Hong; Ma, Ou; Huang, Hui; Cantor, Alan B; Friedman, Alan D

    2016-01-01

    Src phosphorylates Runx1 on one central and four C-terminal tyrosines. We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter. Mutation of the four Runx1 C-terminal tyrosines to aspartate or glutamate to mimic phosphorylation increases trans-activation of the reporter in 293T cells and allows induction of Cebpa or Pu.1 mRNAs in 32Dcl3 myeloid cells, whereas mutation of these residues to phenylalanine to prevent phosphorylation obviates these effects. Three mechanisms contribute to increased Runx1 activity upon tyrosine modification as follows: increased stability, reduced histone deacetylase (HDAC) interaction, and increased DNA binding. Mutation of the five modified Runx1 tyrosines to aspartate markedly reduced co-immunoprecipitation with HDAC1 and HDAC3, markedly increased stability in cycloheximide or in the presence of co-expressed Cdh1, an E3 ubiquitin ligase coactivator, with reduced ubiquitination, and allowed DNA-binding in gel shift assay similar to wild-type Runx1. In contrast, mutation of these residues to phenylalanine modestly increased HDAC interaction, modestly reduced stability, and markedly reduced DNA binding in gel shift assays and as assessed by chromatin immunoprecipitation with the -14-kb Pu.1 or +37-kb Cebpa enhancers after stable expression in 32Dcl3 cells. Affinity for CBFβ, the Runx1 DNA-binding partner, was not affected by these tyrosine modifications, and in vitro translated CBFβ markedly increased DNA affinity of both the translated phenylalanine and aspartate Runx1 variants. Finally, further supporting a positive role for Runx1 tyrosine phosphorylation during granulopoiesis, mutation of the five Src-modified residues to aspartate but not phenylalanine allows Runx1 to increase Cebpa and granulocyte colony formation by Runx1-deleted murine marrow. PMID:26598521

  16. Increasing Physical Activity during the School Day through Physical Activity Classes: Implications for Physical Educators

    ERIC Educational Resources Information Center

    Adkins, Megan; Bice, Matt; Bartee, Todd; Heelan, Kate

    2015-01-01

    Across the nation schools are adopting health and wellness policies, specifically physical activity (PA) initiatives that aid healthy long-term lifestyles. Interest has been generated about the inclusion of physical activity classes to complement existing physical education classes. Furthermore, discussion has evolved as to if additional…

  17. Connecting active living research and public policy: transdisciplinary research and policy interventions to increase physical activity.

    PubMed

    Schilling, Joseph M; Giles-Corti, Billie; Sallis, James F

    2009-01-01

    National and international organizations recommend creation of environments that support physical activity where people live, work, play, study, and travel. Policy changes can lead to activity-supportive environments and incentives. Research on environmental and policy influences on physical activity is well underway in many countries. An important use of the research is to inform policy debates, but the "translation" of research to policy is an emerging science. The papers in this supplement were presented at the 2008 Active Living Research Conference whose theme was "Connecting Active Living Research to Policy Solutions." The papers include evaluations of policy initiatives and research that suggests promising new policies. Commentaries propose principles for improving the translation of research to policy. Improving the rigor of research, asking policy-relevant questions, presenting country-specific data, and effectively communicating findings to policy makers are likely to contribute to greater impact of research on policy processes. PMID:19190567

  18. 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…

  19. 26 CFR 1.280C-4 - Credit for increasing research activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Credit for increasing research activities. 1... increasing research activities. (a) In general. The election under section 280C(c)(3) to have the provisions... 41(a) determined by the method provided in section 280C(c)(3)(B) on an original return for...

  20. Evidence-Based Practice Guideline: Increasing Physical Activity in Schools--Kindergarten through 8th Grade

    ERIC Educational Resources Information Center

    Bagby, Karen; Adams, Susan

    2007-01-01

    Because of the growing obesity epidemic across all age groups in the United States, interventions to increase physical activity and reduce sedentary behaviors have become a priority. Evidence is growing that interventions to increase physical activity and reduce sedentary behaviors have positive results and are generally inexpensive to implement.…

  1. Men on the Move: A Pilot Program to Increase Physical Activity among African American Men

    ERIC Educational Resources Information Center

    Griffith, Derek M.; Allen, Julie Ober; Johnson-Lawrence, Vicki; Langford, Aisha

    2014-01-01

    Despite the important contribution increasing physical activity levels may play in reducing chronic disease morbidity and mortality, there is a paucity of interventions and research indicating how to improve physical activity levels in African American men. "Men on the Move" was a pilot study to increase African American men's…

  2. Increasing Activity Attendance and Engagement in Individuals with Dementia Using Descriptive Prompts

    ERIC Educational Resources Information Center

    Brenske, Shasta; Rudrud, Eric H.; Schulze, Kimberly A.; Rapp, John T.

    2008-01-01

    The effects of providing descriptive prompts to increase activity attendance and engagement in 6 individuals with dementia were evaluated using a reversal design. The results showed that providing descriptive prompts increased activity attendance and engagement for all participants. The results support the use of antecedent interventions for…

  3. 26 CFR 1.41-1 - Credit for increasing research activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 1 2011-04-01 2009-04-01 true Credit for increasing research activities. 1.41-1... TAXES Credits Against Tax § 1.41-1 Credit for increasing research activities. (a) Amount of credit. The...). (b) Introduction to regulations under section 41. (1) Sections 1.41-2 through 1.41-8 and...

  4. 26 CFR 1.41-1 - Credit for increasing research activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Credit for increasing research activities. 1.41-1... TAXES Credits Against Tax § 1.41-1 Credit for increasing research activities. (a) Amount of credit. The...). (b) Introduction to regulations under section 41. (1) Sections 1.41-2 through 1.41-8 and...

  5. Gain of function AMP-activated protein kinase γ3 mutation (AMPKγ3R200Q) in pig muscle increases glycogen storage regardless of AMPK activation.

    PubMed

    Scheffler, Tracy L; Park, Sungkwon; Roach, Peter J; Gerrard, David E

    2016-06-01

    Chronic activation of AMP-activated protein kinase (AMPK) increases glycogen content in skeletal muscle. Previously, we demonstrated that a mutation in the ryanodine receptor (RyR1(R615C)) blunts AMPK phosphorylation in longissimus muscle of pigs with a gain of function mutation in the AMPKγ3 subunit (AMPKγ3(R200Q)); this may decrease the glycogen storage capacity of AMPKγ3(R200Q) + RyR1(R615C) muscle. Therefore, our aim in this study was to utilize our pig model to understand how AMPKγ3(R200Q) and AMPK activation contribute to glycogen storage and metabolism in muscle. We selected and bred pigs in order to generate offspring with naturally occurring AMPKγ3(R200Q), RyR1(R615C), and AMPKγ3(R200Q) + RyR1(R615C) mutations, and also retained wild-type littermates (control). We assessed glycogen content and parameters of glycogen metabolism in longissimus muscle. Regardless of RyR1(R615C), AMPKγ3(R200Q) increased the glycogen content by approximately 70%. Activity of glycogen synthase (GS) without the allosteric activator glucose 6-phosphate (G6P) was decreased in AMPKγ3(R200Q) relative to all other genotypes, whereas both AMPKγ3(R200Q) and AMPKγ3(R200Q) + RyR1(R615C) muscle exhibited increased GS activity with G6P. Increased activity of GS with G6P was not associated with increased abundance of GS or hexokinase 2. However, AMPKγ3(R200Q) enhanced UDP-glucose pyrophosphorylase 2 (UGP2) expression approximately threefold. Although UGP2 is not generally considered a rate-limiting enzyme for glycogen synthesis, our model suggests that UGP2 plays an important role in increasing flux to glycogen synthase. Moreover, we have shown that the capacity for glycogen storage is more closely related to the AMPKγ3(R200Q) mutation than activity. PMID:27302990

  6. Evidence-based practice guideline: increasing physical activity in schools--kindergarten through 8th grade.

    PubMed

    Bagby, Karen; Adams, Susan

    2007-06-01

    Because of the growing obesity epidemic across all age groups in the United States, interventions to increase physical activity and reduce sedentary behaviors have become a priority. Evidence is growing that interventions to increase physical activity and reduce sedentary behaviors have positive results and are generally inexpensive to implement. National and international health organizations are calling for a comprehensive approach for reducing obesity in children that includes increasing physical activity in the school setting. Although the call to increase activity levels in schools is clear, little guidance has been given to schools on specific methods to accomplish this task. This article provides an overview of an evidence-based guideline developed by a physical education teacher and a school nurse to provide inexpensive, easy-to-implement, effective strategies to increase physical activity in students. Tools are also included in the guideline to measure the effectiveness of the intervention. PMID:17536917

  7. Use of an open-loop system to increase physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study evaluated the effectiveness of an open-loop system that reinforces physical activity with TV watching to increase children’s physical activity. Non-overweight, sedentary boys and girls (8-12 y) were randomized to a group that received feedback of activity counts + reinforcement for physic...

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  9. Texting to increase physical activity among teenagers (TXT Me!): Rationale, design, and methods proposal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity decreases from childhood through adulthood. Among youth, teenagers (teens) achieve the lowest levels of physical activity, and high school age youth are particularly at risk of inactivity. Effective methods are needed to increase youth physical activity in a way that can be maintai...

  10. The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol

    PubMed Central

    2011-01-01

    Background Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. Methods A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. Discussion If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and m

  11. Botulinum toxin complex increases paracellular permeability in intestinal epithelial cells via activation of p38 mitogen-activated protein kinase.

    PubMed

    Miyashita, Shin-Ichiro; Sagane, Yoshimasa; Inui, Ken; Hayashi, Shintaro; Miyata, Keita; Suzuki, Tomonori; Ohyama, Tohru; Watanabe, Toshihiro; Niwa, Koichi

    2013-12-30

    Clostridium botulinum produces a large toxin complex (L-TC) that increases paracellular permeability in intestinal epithelial cells by a mechanism that remains unclear. Here, we show that mitogen-activated protein kinases (MAPKs) are involved in this permeability increase. Paracellular permeability was measured by FITC-dextran flux through a monolayer of rat intestinal epithelial IEC-6 cells, and MAPK activation was estimated from western blots. L-TC of C. botulinum serotype D strain 4947 increased paracellular dextran flux and activated extracellular signal-regulated kinase (ERK), p38, but not c-Jun N-terminal kinase (JNK) in IEC-6 cells. The permeability increase induced by L-TC was abrogated by the p38 inhibitor SB203580. These results indicate that L-TC increases paracellular permeability by activating p38, but not JNK and ERK. PMID:23884081

  12. Longterm persistence of proteolytic activities in frass of Blattella germanica increases its allergenic potential.

    PubMed

    Erban, T; Hubert, J

    2011-06-01

    Chromogenic microplate assays in 96 wells were used to determine the stability of enzyme activity in frass of Blattella germanica (Blattodea: Blattellidae). Frass samples were exposed to controlled conditions [temperature 15-35 °C and/or 53-100% relative humidity (RH)] and to household conditions (apartment). Exposure times were 0 (control), 90, 183 and 276 days. Starch digestion and cellulolytic activities decreased during exposure. Non-specific proteolytic activities were affected by changes in selective proteolytic activities. Activities towards AAPpNA and SA(3) pNA strongly increased at 100% RH, indicating the possible influence of microorganisms growing on frass. Activities towards BApNA and ArgpNA decreased with increasing decomposition time, whereas activity towards ZRRpNA was not influenced by exposure time. The largest decrease in activities towards ArgpNA and BApNA occurred at temperatures of 15 °C, 30 °C and 35 °C and at 100% RH. Activities towards BApNA and ZRRpNA were very stable under different temperature and RH conditions; this was confirmed by findings showing that these activities were stable in the experimental apartment. In comparison with the control, activities towards ZRRpNA and BApNA after 276 days decreased by 1% and 19%, respectively. The longterm persistence of proteolytic activities in cockroach frass increases their allergenic hazard potential. PMID:21198710

  13. Vertebrate blood cell volume increases with temperature: implications for aerobic activity

    PubMed Central

    Zenil-Ferguson, Rosana

    2014-01-01

    Aerobic activity levels increase with body temperature across vertebrates. Differences in these levels, from highly active to sedentary, are reflected in their ecology and behavior. Yet, the changes in the cardiovascular system that allow for greater oxygen supply at higher temperatures, and thus greater aerobic activity, remain unclear. Here we show that the total volume of red blood cells in the body increases exponentially with temperature across vertebrates, after controlling for effects of body size and taxonomy. These changes are accompanied by increases in relative heart mass, an indicator of aerobic activity. The results point to one way vertebrates may increase oxygen supply to meet the demands of greater activity at higher temperatures. PMID:24765580

  14. The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity.

    PubMed

    Broeders, Evie P M; Nascimento, Emmani B M; Havekes, Bas; Brans, Boudewijn; Roumans, Kay H M; Tailleux, Anne; Schaart, Gert; Kouach, Mostafa; Charton, Julie; Deprez, Benoit; Bouvy, Nicole D; Mottaghy, Felix; Staels, Bart; van Marken Lichtenbelt, Wouter D; Schrauwen, Patrick

    2015-09-01

    The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans. PMID:26235421

  15. Diabetes or peroxisome proliferator-activated receptor alpha agonist increases mitochondrial thioesterase I activity in heart

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of pr...

  16. Feasibility and Effects of Short Activity Breaks for Increasing Preschool-Age Children's Physical Activity Levels

    ERIC Educational Resources Information Center

    Alhassan, Sofiya; Nwaokelemeh, Ogechi; Mendoza, Albert; Shitole, Sanyog; Puleo, Elaine; Pfeiffer, Karin A.; Whitt-Glover, Melicia C.

    2016-01-01

    Background: We examined the effects of short bouts of structured physical activity (SBS-PA) implemented within the classroom setting as part of designated gross-motor playtime on preschoolers PA. Methods: Preschools were randomized to SBS-PA (centers, N = 5; participants, N = 141) or unstructured free playtime (UPA) (centers, N = 5; participants,…

  17. Fas-Induced Apoptosis Increases Hepatocyte Tissue Factor Procoagulant Activity In Vitro and In Vivo

    PubMed Central

    Lopez, Michelle; Kopec, Anna K.; Joshi, Nikita; Geddings, Julia E.; Cline, Holly; Towery, Keara L.; Rockwell, Cheryl E.; Mackman, Nigel; Luyendyk, James P.

    2014-01-01

    Hepatocyte (HPC) apoptosis occurs in association with hepatotoxic responses and chronic liver disease, and is coupled to activation of the blood coagulation cascade. HPCs have been shown to express tissue factor (TF), the primary activator of blood coagulation, in a form that lacks procoagulant activity. In this study, we determined the effect of inducing HPC apoptosis on the procoagulant activity of TF. Treatment of primary mouse HPCs with the Fas death receptor agonist (anti-CD95 antibody, Jo2) triggered apoptosis as shown by cleavage of caspase-3, increased caspase-3 proteolytic activity, and cell surface exposure of phosphatidylserine (PS). Jo2-induced apoptosis significantly increased TF-dependent factor Xa generation by HPCs. Moreover, Jo2 treatment was associated with increased levels of microparticle-associated TF procoagulant activity in the culture medium. Pretreatment with a caspase-3 inhibitor significantly reduced Jo2-induced HPC TF activity and prevented the increase in microparticle-associated TF procoagulant activity. Application of the high-affinity PS-binding protein lactadherin inhibited TF-dependent factor Xa generation by Jo2-treated HPCs and dramatically reduced microparticle-associated TF procoagulant activity. Treatment of wild-type mice with a sublethal dose of Jo2 was associated with a robust increase in the activation of coagulation as measured by plasma thrombin-antithrombin (TAT) levels; whereas mice with liver-specific TF deficiency had significantly lower TAT levels. Overall, the results indicate that Fas-initiated, caspase-3-dependent HPC apoptosis increases TF procoagulant activity through a mechanism involving PS externalization. This suggests that activation of liver TF likely contributes to the procoagulant state associated with HPC apoptosis in liver toxicity and disease. PMID:25015658

  18. Simulated ischaemia-reperfusion conditions increase xanthine dehydrogenase and oxidase activities in rat brain slices.

    PubMed

    Battelli, M G; Buonamici, L; Virgili, M; Abbondanza, A; Contestabile, A

    1998-01-01

    Xanthine dehydrogenase and oxidase activities increased by 87% in rat brain slices after 30 min in vitro ischaemia. A further 41% increase was induced by 30 min simulated reperfusion of ischaemic slices. No conversion from the dehydrogenase to the oxidase activity was observed. The increment of enzyme activity was not due to neosynthesis of the enzyme, since it was not affected by the addition of cycloheximide during the ischaemic incubation. The increased oxygen-dependent form of the enzyme could aggravate the ischaemic brain injury by free radicals production, in particular after reperfusion. PMID:9460697

  19. The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

    NASA Technical Reports Server (NTRS)

    Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

    1978-01-01

    During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

  20. Lung cancer chemotherapy agents increase procoagulant activity via protein disulfide isomerase-dependent tissue factor decryption.

    PubMed

    Lysov, Zakhar; Swystun, Laura L; Kuruvilla, Sara; Arnold, Andrew; Liaw, Patricia C

    2015-01-01

    Lung cancer patients undergoing chemotherapy have an elevated risk for thrombosis. However, the mechanisms by which chemotherapy agents increase the risk for thrombosis remains unclear. The aim of this study was to determine the mechanism(s) by which lung cancer chemotherapy agents cisplatin, carboplatin, gemcitabine, and paclitaxel elicit increased tissue factor activity on endothelial cells, A549 cells, and monocytes. Tissue factor activity, tissue factor antigen, and phosphatidylserine exposure were measured on chemotherapy-treated human umbilical vein endothelial cells (HUVEC), A549 cells, and monocytes. Cell surface protein disulfide isomerase (PDI) and cell surface free thiol levels were measured on HUVEC and A549 non-small cell lung carcinoma cells. Treatment of HUVECs, A549 cells, and monocytes with lung cancer chemotherapy significantly increased cell surface tissue factor activity. However, elevated tissue factor antigen levels were observed only on cisplatin-treated and gemcitabine-treated monocytes. Cell surface levels of phosphatidylserine were increased on HUVEC and monocytes treated with cisplatin/gemcitabine combination therapy. Chemotherapy also resulted in increased cell surface levels of PDI and reduced cell surface free thiol levels. Glutathione treatment and PDI inhibition, but not phosphatidylserine inhibition, attenuated tissue factor activity. Furthermore, increased tissue factor activity was reversed by reducing cysteines with dithiothreitol. These studies are the first to demonstrate that lung cancer chemotherapy agents increase procoagulant activity on endothelial cells and A549 cells by tissue factor decryption through a disulfide bond formation in a PDI-dependent mechanism. PMID:24911456

  1. Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway

    PubMed Central

    2014-01-01

    Background Therapeutic hypothermia is a treatment modality that is increasingly used to improve clinical neurological outcomes for ischemia-reperfusion injury-mediated diseases. Antibody-initiated classical complement pathway activation has been shown to contribute to ischemia-reperfusion injury in multiple disease processes. However, how therapeutic hypothermia affects complement activation is unknown. Our goal was to measure the independent effect of temperature on complement activation, and more specifically, examine the relationship between clinical hypothermia temperatures (31–33°C), and complement activation. Methods Antibody-sensitized erythrocytes were used to assay complement activation at temperatures ranging from 0-41°C. Individual complement pathway components were assayed by ELISA, Western blot, and quantitative dot blot. Peptide Inhibitor of complement C1 (PIC1) was used to specifically inhibit activation of C1. Results Antibody-initiated complement activation resulting in eukaryotic cell lysis was increased by 2-fold at 31°C compared with 37°C. Antibody-initiated complement activation in human serum increased as temperature decreased from 37°C until dramatically decreasing at 13°C. Quantitation of individual complement components showed significantly increased activation of C4, C3, and C5 at clinical hypothermia temperatures. In contrast, C1s activation by heat-aggregated IgG decreased at therapeutic hypothermia temperatures consistent with decreased enzymatic activity at lower temperatures. However, C1q binding to antibody-coated erythrocytes increased at lower temperatures, suggesting that increased classical complement pathway activation is mediated by increased C1 binding at therapeutic hypothermia temperatures. PIC1 inhibited hypothermia-enhanced complement-mediated cell lysis at 31°C by up to 60% (P = 0.001) in a dose dependent manner. Conclusions In summary, therapeutic hypothermia temperatures increased antibody

  2. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

    PubMed Central

    Davis, Zachary W.; Chapman, Barbara

    2015-01-01

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. SIGNIFICANCE STATEMENT Patterned spontaneous neural activity that occurs during development is known to be necessary for the proper formation of neural circuits. However, it is unknown whether the spontaneous activity alone is sufficient to drive the maturation of the functional properties of neurons. Our work demonstrates for the first time an acceleration in the maturation of neural function as a consequence of driving patterned spontaneous activity during development. This work has implications for our understanding of how neural circuits can be modified actively to improve function prematurely or to recover from injury with guided interventions of patterned neural activity. PMID:26511250

  3. Approximation of the first passage time density of a Wiener process to an exponentially decaying boundary by two-piecewise linear threshold. Application to neuronal spiking activity.

    PubMed

    Tamborrino, Massimiliano

    2016-06-01

    The first passage time density of a diffusion process to a time varying threshold is of primary interest in different fields. Here, we consider a Brownian motion in presence of an exponentially decaying threshold to model the neuronal spiking activity. Since analytical expressions of the first passage time density are not available, we propose to approximate the curved boundary by means of a continuous two-piecewise linear threshold. Explicit expressions for the first passage time density towards the new boundary are provided. First, we introduce different approximating linear thresholds. Then, we describe how to choose the optimal one minimizing the distance to the curved boundary, and hence the error in the corresponding passage time density. Theoretical means, variances and coefficients of variation given by our method are compared with empirical quantities from simulated data. Moreover, a further comparison with firing statistics derived under the assumption of a small amplitude of the time-dependent change in the threshold, is also carried out. Finally, maximum likelihood and moment estimators of the parameters of the model are derived and applied on simulated data. PMID:27106189

  4. Increased Vacuolar ATPase Activity Correlated With CAM Induction in Mesembryanthemum crystallinum and Kalanchoë blossfeldiana cv. Tom Thumb.

    PubMed

    Struve, I; Weber, A; Lüttge, U; Ball, E; Smith, J A

    1985-01-01

    Vacuolar ATPase activities were determined by differential inhibition of homogenates of isolated protoplasts (using the inhibitors molybdate for acid phosphatases, vanadate for plasmalemma ATPase, azide for mitochondrial ATPase, and phlorizin for chloroplast ATPase) and in preparations of isolated vacuoles of Mesembryanthemum crystallinum and Kalanchoë blossfeldiana cv. Tom Thumb. Crassulacean acid metabolism (CAM) was induced in M. crystallinum by NaCl-salinity and in K. blossfeldiana by short-day treatments. Vacuolar ATPase activities increased several-fold during the transition from C(3) photosynthesis to CAM. The increase was quantitatively related to the rates of nocturnal maliacid accumulation in CAM assuming a stoichiometry of 2 H(+) pumped into the vacuole for 1 ATP hydrolyzed and 1 malate(2-) anion transported by secondary flux coupling. In M. crystallinum increased vacuolar ATPase activities were truly correlated with the degree of CAM expressed and not with NaCl accumulation due to the salinity treatment. Some properties of the vacuolar A TPase of M. crystallinum characterized in vacuole preparations were a pH-optimum near 8.0, an apparent K(m) (MgATP(2-)) of 0.20 to 0.29 mM, and an approximately 70 % inhibition by 50 mM nitrate. PMID:23195866

  5. 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

  6. Increased writing activity in neurological conditions: a review and clinical study.

    PubMed Central

    van Vugt, P; Paquier, P; Kees, L; Cras, P

    1996-01-01

    Increased writing activity in a 70 year old, right handed man presenting with a history of alcohol misuse and maturity onset diabetes is reported. Brain CT disclosed corticosubcortical atrophy and 99mTc-HMPAO SPECT disclosed severe bilateral frontal hypoperfusion more prominent on the right. The patient's neuropsychological symptomatology consisted of severe (verbal) aspontaneity, intermittent utilisation behaviour, and pronounced increased writing activity, which mainly consisted of a perseverative, micrographic written reproduction of visually or verbally perceived language fragments. Several neurological causes of increased writing activity and the equivocal terminology met in the medical literature are reviewed. A distinction between hypergraphia and automatic writing behaviour is proposed. It is concluded that our patient's increased writing activity may be characterised as automatic writing behaviour. Images PMID:8937347

  7. Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection

    PubMed Central

    Guthrie, Brandon S.; Schmidt, Rebecca L.; Jamieson, Amanda; Merkel, Patricia; Knight, Vijaya; Cole, Caroline M.; Raulet, David H.; Lenz, Laurel L.

    2016-01-01

    Natural killer (NK) cells produce interferon (IFN)-γ and thus have been suggested to promote type I immunity during bacterial infections. Yet, Listeria monocytogenes (Lm) and some other pathogens encode proteins that cause increased NK cell activation. Here, we show that stimulation of NK cell activation increases susceptibility during Lm infection despite and independent from robust NK cell production of IFNγ. The increased susceptibility correlated with IL-10 production by responding NK cells. NK cells produced IL-10 as their IFNγ production waned and the Lm virulence protein p60 promoted induction of IL-10 production by mouse and human NK cells. NK cells consequently exerted regulatory effects to suppress accumulation and activation of inflammatory myeloid cells. Our results reveal new dimensions of the role played by NK cells during Lm infection and demonstrate the ability of this bacterial pathogen to exploit the induction of regulatory NK cell activity to increase host susceptibility. PMID:27295349

  8. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields.

    PubMed

    Davis, Zachary W; Chapman, Barbara; Cheng, Hwai-Jong

    2015-10-28

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. PMID:26511250

  9. Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection.

    PubMed

    Clark, Sarah E; Filak, Holly C; Guthrie, Brandon S; Schmidt, Rebecca L; Jamieson, Amanda; Merkel, Patricia; Knight, Vijaya; Cole, Caroline M; Raulet, David H; Lenz, Laurel L

    2016-06-01

    Natural killer (NK) cells produce interferon (IFN)-γ and thus have been suggested to promote type I immunity during bacterial infections. Yet, Listeria monocytogenes (Lm) and some other pathogens encode proteins that cause increased NK cell activation. Here, we show that stimulation of NK cell activation increases susceptibility during Lm infection despite and independent from robust NK cell production of IFNγ. The increased susceptibility correlated with IL-10 production by responding NK cells. NK cells produced IL-10 as their IFNγ production waned and the Lm virulence protein p60 promoted induction of IL-10 production by mouse and human NK cells. NK cells consequently exerted regulatory effects to suppress accumulation and activation of inflammatory myeloid cells. Our results reveal new dimensions of the role played by NK cells during Lm infection and demonstrate the ability of this bacterial pathogen to exploit the induction of regulatory NK cell activity to increase host susceptibility. PMID:27295349

  10. Drought offset ecological restoration program-induced increase in vegetation activity in the Beijing-Tianjin Sand Source Region, China.

    PubMed

    Wu, Zhitao; Wu, Jianjun; He, Bin; Liu, Jinghui; Wang, Qianfeng; Zhang, Hong; Liu, Yong

    2014-10-21

    To improve the ecological conditions, the Chinese government adopted six large-scale ecological restoration programs including 'Three-North Shelterbelt Project', "Grain for Green Project" and "Beijing-Tianjin Sand Source Control Project". Meanwhile, these ecologically vulnerable areas have experienced frequent droughts. However, little attention has been paid to the impact of drought on the effectiveness of these programs. Taking Beijing-Tianjin Sand Source Region (BTSSR) as study area, we investigated the role of droughts and ecological restoration program on trends of vegetation activities and to address the question of a possible "drought signal" in assessing effectiveness of ecological restoration program. The results demonstrate the following: (1) Vegetation activity increased in the BTSSR during 2000-2010, with 58.44% of the study area showing an increased NDVI, of which 11.80% had a significant increase at 0.95 confidential level. The decreasing NDVI trends were mainly concentrated in a southwest-to-northeast strip in the study area. (2) Drought was the main driving force for a decreasing trend of vegetation activity in the southwest-to-northeast regions of the BTSSR at the regional and spatial scales. Summer droughts in 2007 and 2009 contributed to the decreasing trend in NDVI. The severe and extreme droughts in summer reduced the NDVI by approximately 13.06% and 23.55%, respectively. (3) The residual analysis result showed that human activities, particularly the ecological restoration programs, have a positive impact on vegetation change. Hence, the decreasing trends in the southwest-to-northeast regions of the BTSSR cannot be explained by the improper ecological restoration program and is partly explained by droughts, especially summer droughts. Therefore, drought offset the ecological restoration program-induced increase in vegetation activity in the BTSSR. PMID:25203241

  11. Energy expended playing video console games: an opportunity to increase children's physical activity?

    PubMed

    Maddison, Ralph; Mhurchu, Cliona Ni; Jull, Andrew; Jiang, Yannan; Prapavessis, Harry; Rodgers, Anthony

    2007-08-01

    This study sought to quantify the energy expenditure and physical activity associated with playing the "new generation" active and nonactive console-based video games in 21 children ages 10-14 years. Energy expenditure (kcal) derived from oxygen consumption (VO2) was continuously assessed while children played nonactive and active console video games. Physical activity was assessed continuously using the Actigraph accelerometer. Significant (p < .001) increases from baseline were found for energy expenditure (129-400%), heart rate (43-84%), and activity counts (122-1288 versus 0-23) when playing the active console video games. Playing active console video games over short periods of time is similar in intensity to light to moderate traditional physical activities such as walking, skipping, and jogging. PMID:18019591

  12. Physical activity compensates for increased mortality risk among older people with poor muscle strength.

    PubMed

    Portegijs, E; Rantanen, T; Sipilä, S; Laukkanen, P; Heikkinen, E

    2007-10-01

    The aim of the study was to determine whether habitual physical activity can compensate for the increased mortality risk among older people with poor muscle strength. Mortality was followed up for 10 years after laboratory examination in 558 community dwelling 75- and 80-year-old men and women. Maximal isometric strength of five muscle groups was measured and tertile cut-off points were used to categorize participants. Participants, who reported moderate physical activity for at least 4 h a week, were categorized as physically active and the others as sedentary. High muscle strength and physical activity both protected from mortality, but their effect was not additive. Within each muscle strength tertile, physically active people had a lower mortality risk than sedentary people, the effect being most pronounced among those with lower strength in all muscle groups. A high level of physical activity may thus compensate for the increased mortality associated with low muscle strength. PMID:17166169

  13. Experimental determination of water activity for binary aqueous cerium(III) ionic solutions: application to an assessment of the predictive capability of the binding mean spherical approximation model.

    PubMed

    Ruas, Alexandre; Simonin, Jean-Pierre; Turq, Pierre; Moisy, Philippe

    2005-12-01

    This work is aimed at a description of the thermodynamic properties of actinide salt solutions at high concentration. The predictive capability of the binding mean spherical approximation (BIMSA) theory to describe the thermodynamic properties of electrolytes is assessed in the case of aqueous solutions of lanthanide(III) nitrate and chloride salts. Osmotic coefficients of cerium(III) nitrate and chloride were calculated from other lanthanide(III) salts properties. In parallel, concentrated binary solutions of cerium nitrate were prepared in order to measure experimentally its water activity and density as a function of concentration, at 25 degrees C. Water activities of several binary solutions of cerium chloride were also measured to check existing data on this salt. Then, the properties of cerium chloride and cerium nitrate solutions were compared within the BIMSA model. Osmotic coefficient values for promethium nitrate and promethium chloride given by this theory are proposed. Finally, water activity measurements were made to examine the fact that the ternary system Ce(NO3)3/HNO3/H2O and the quaternary system Ce(NO3)3/HNO3/N2H5NO3/H2O may be regarded as "simple solutions" (in the sense of Zdanovskii and Mikulin). PMID:16854002

  14. Playground designs to increase physical activity levels during school recess: a systematic review.

    PubMed

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M

    2014-04-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A systematic search of seven databases was made from the July 1 to July 5, 2012, leading to a final set of eight studies (a total of 2,383 subjects-599 "preschoolers" and 1,784 "schoolchildren") meeting the inclusion criteria. These studies were classified according to the intervention used: playground markings, game equipment, playground markings plus physical structures, and playground markings plus game equipment. The results of these studies indicate that the strategies analyzed do have the potential to increase physical activity levels during recess. The cumulative evidence was (a) that interventions based on playground markings, game equipment, or a combination of the two, do not seem to increase the physical activity of preschoolers and schoolchildren during recess and (ii) that interventions based on playground markings plus physical structures do increase the physical activity of schoolchildren during recess in the short to medium term. PMID:23836828

  15. Approximate option pricing

    SciTech Connect

    Chalasani, P.; Saias, I.; Jha, S.

    1996-04-08

    As increasingly large volumes of sophisticated options (called derivative securities) are traded in world financial markets, determining a fair price for these options has become an important and difficult computational problem. Many valuation codes use the binomial pricing model, in which the stock price is driven by a random walk. In this model, the value of an n-period option on a stock is the expected time-discounted value of the future cash flow on an n-period stock price path. Path-dependent options are particularly difficult to value since the future cash flow depends on the entire stock price path rather than on just the final stock price. Currently such options are approximately priced by Monte carlo methods with error bounds that hold only with high probability and which are reduced by increasing the number of simulation runs. In this paper the authors show that pricing an arbitrary path-dependent option is {number_sign}-P hard. They show that certain types f path-dependent options can be valued exactly in polynomial time. Asian options are path-dependent options that are particularly hard to price, and for these they design deterministic polynomial-time approximate algorithms. They show that the value of a perpetual American put option (which can be computed in constant time) is in many cases a good approximation to the value of an otherwise identical n-period American put option. In contrast to Monte Carlo methods, the algorithms have guaranteed error bounds that are polynormally small (and in some cases exponentially small) in the maturity n. For the error analysis they derive large-deviation results for random walks that may be of independent interest.

  16. Physical Activity and Executive Control: Implications for Increased Cognitive Health during Older Adulthood

    ERIC Educational Resources Information Center

    Hillman, Charles H.; Belopolsky, Artem V.; Snook, Erin M.; Kramer, Arthur F.; McAuley, Edward

    2004-01-01

    Electrocortical and behavioral responses of low, moderate, and high physically active older adults where compared with a younger control group on neutral and incompatible conditions of a flankers task. Compared to younger adults, high and moderate active older adults exhibited increased event-related potentials component P3 amplitude for the…

  17. Newspaper Content Analysis in Evaluation of a Community-Based Participatory Project to Increase Physical Activity

    ERIC Educational Resources Information Center

    Granner, Michelle L.; Sharpe, Patricia A.; Burroughs, Ericka L.; Fields, Regina; Hallenbeck, Joyce

    2010-01-01

    This study conducted a newspaper content analysis as part of an evaluation of a community-based participatory research project focused on increasing physical activity through policy and environmental changes, which included activities related to media advocacy and media-based community education. Daily papers (May 2003 to December 2005) from both…

  18. 26 CFR 1.280C-4 - Credit for increasing research activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Credit for increasing research activities. 1... research activities. (a) In general. The election under section 280C(c)(3) to have the provisions of...) determined by the method provided in section 280C(c)(3)(B) on an original return for the taxable year,...

  19. Focused Campaign Increases Activity among Participants in "Nature's Notebook," a Citizen Science Project

    ERIC Educational Resources Information Center

    Crimmins, Theresa M.; Weltzin, Jake F.; Rosemartin, Alyssa H.; Surina, Echo M.; Marsh, Lee; Denny, Ellen G.

    2014-01-01

    Science projects, which engage non-professional scientists in one or more stages of scientific research, have been gaining popularity; yet maintaining participants' activity level over time remains a challenge. The objective of this study was to evaluate the potential for a short-term, focused campaign to increase participant activity in a…

  20. Increasing Student Physical Activity during the School Day: Opportunities for the Physical Educator

    ERIC Educational Resources Information Center

    Brewer, Joan D.; Luebbers, Paul E.; Shane, Shawna D.

    2009-01-01

    America is facing an obesity epidemic--one that is difficult to ignore. In order to combat the nation's obesity crisis, it is imperative that schools find ways to increase the physical activity levels of students during the school day, as well as encourage additional activity outside of school. By teaching youth to incorporate physical activity…

  1. Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death.

    PubMed

    Soler, David C; Ohtola, Jennifer; Sugiyama, Hideaki; Rodriguez, Myriam E; Han, Ling; Oleinick, Nancy L; Lam, Minh; Baron, Elma D; Cooper, Kevin D; McCormick, Thomas S

    2016-06-01

    Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3(+) T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6-59.9%) at Pc 4 doses ranging from 0-300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6-81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300 nM, p < 0.001 between 50 and 150 nM, n = 8). Treg uptake was diminished relative to other T cells. Cutaneous T cell lymphoma (CTCL) T cells appeared to take up somewhat more Pc 4 than normal resting T cells at 100 and 150 nm Pc 4. Confocal imaging revealed that Pc 4 localized in cytoplasmic organelles, with approximately half of the Pc 4 co-localized with mitochondria in T cells. Thus, Pc 4-PDT exerts an enhanced apoptotic effect on activated CD3(+) T cells that may be exploited in targeting T cell-mediated skin

  2. Effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity

    PubMed Central

    Zhao, Xiaoguang; Tsujimoto, Takehiko; Kim, Bokun; Katayama, Yasutomi; Wakaba, Kyousuke; Wang, Zhennan; Tanaka, Kiyoji

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity and to verify whether the rate of change in foot structure is related to that in ankle muscle strength. [Subjects and Methods] Twenty-seven adults with obesity completed a 12-week program in which the intensity of physical activity performed was gradually increased. Physical activity was monitored using a three-axis accelerometer. Foot structure was assessed using a three-dimensional foot scanner, while ankle muscle strength was measured using a dynamometry. [Results] With the increasing physical activity, the participants’ feet became thinner (the rearfoot width, instep height, and girth decreased) and the arch became higher (the arch height index increased) and stiffer (the arch stiffness index increased); the ankle muscle strength also increased after the intervention. Additionally, the changes in the arch height index and arch stiffness index were not associated with changes in ankle muscle strength. [Conclusion] Increasing physical activity may be one possible approach to improve foot structure and function in individuals with obesity.

  3. Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production

    PubMed Central

    Colin, Sophie; Briand, Olivier; Touche, Véronique; Wouters, Kristiaan; Baron, Morgane; Pattou, François; Hanf, Rémy; Tailleux, Anne; Chinetti, Giulia; Staels, Bart; Lestavel, Sophie

    2013-01-01

    Aims Peroxisome Proliferator-Activated Receptor (PPAR) α is a transcription factor controlling lipid metabolism in liver, heart, muscle and macrophages. PPARα-activation increases plasma HDL-cholesterol and exerts hypotriglyceridemic actions via the liver. However, the intestine expresses PPARα, produces HDL and chylomicrons and is exposed to diet-derived PPARα ligands. Therefore, we examined the effects of PPARα-activation on intestinal lipid and lipoprotein metabolism. Methods and Results The impact of PPARα-activation was evaluated in term of HDL-related gene expression in mice, ex-vivo in human jejunal biopsies and in Caco-2/TC7 cells. ApoAI/HDL secretion, cholesterol esterification and trafficking were also studied in-vitro. In parallel to improving plasma lipid profiles and increasing liver and intestinal expression of fatty-acid-oxidation genes, treatment with the dual PPARα/δ-ligand GFT505 resulted in a more pronounced increase of plasma HDL compared to fenofibrate in mice. GFT505, but not fenofibrate, increased the expression of HDL-production genes such as apolipoprotein-AI and ATP-Binding-Cassette-A1 transporter in murine intestines. A similar increase was observed upon PPARα-activation of human biopsies and Caco-2/TC7 cells. Additionally, HDL secretion by Caco-2/TC7 cells increased. Moreover, PPARα-activation decreased the cholesterol-esterification capacity of Caco-2/TC7 cells, modified cholesterol trafficking and reduced apolipoprotein-B secretion. Conclusions PPARα-activation reduces cholesterol esterification, suppresses chylomicron- and increases HDL-secretion by enterocytes. These results identify the intestine as a target organ of PPARα-ligands with entero-hepatic tropism to reduce atherogenic dyslipidemia. PMID:22843443

  4. Increased Mucosal CD4+ T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector

    PubMed Central

    Bukh, Irene; Calcedo, Roberto; Roy, Soumitra; Carnathan, Diane G.; Grant, Rebecca; Qin, Qiuyue; Boyd, Surina; Ratcliffe, Sarah J.; Veeder, Christin L.; Bellamy, Scarlett L.; Betts, Michael R.

    2014-01-01

    ABSTRACT The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4+ T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4+ T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4+ T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4+ T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4+ T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4+ T cells and potentially increases susceptibility to SIV

  5. Increasing western US forest wildfire activity: sensitivity to changes in the timing of spring.

    PubMed

    Westerling, Anthony LeRoy

    2016-06-01

    Prior work shows western US forest wildfire activity increased abruptly in the mid-1980s. Large forest wildfires and areas burned in them have continued to increase over recent decades, with most of the increase in lightning-ignited fires. Northern US Rockies forests dominated early increases in wildfire activity, and still contributed 50% of the increase in large fires over the last decade. However, the percentage growth in wildfire activity in Pacific northwestern and southwestern US forests has rapidly increased over the last two decades. Wildfire numbers and burned area are also increasing in non-forest vegetation types. Wildfire activity appears strongly associated with warming and earlier spring snowmelt. Analysis of the drivers of forest wildfire sensitivity to changes in the timing of spring demonstrates that forests at elevations where the historical mean snow-free season ranged between two and four months, with relatively high cumulative warm-season actual evapotranspiration, have been most affected. Increases in large wildfires associated with earlier spring snowmelt scale exponentially with changes in moisture deficit, and moisture deficit changes can explain most of the spatial variability in forest wildfire regime response to the timing of spring.This article is part of the themed issue 'The interaction of fire and mankind'. PMID:27216510

  6. Increasing Physical Activity in Preschool: A Pilot Study to Evaluate Animal Trackers

    ERIC Educational Resources Information Center

    Williams, Christine L.; Carter, Betty Jean; Kibbe, Debra L.; Dennison, David

    2009-01-01

    Objective: This report describes a pilot study to evaluate Animal Trackers (AT), a preschool program designed to (1) increase structured physical activity (PA) during the preschool day; (2) increase practice of gross motor skills; (3) provide teachers with an easy-to-use PA program regardless of teacher experience; and (4) implement a teacher…

  7. USING THE Internet TO INCREASE Physical Activity IN A FAITH COMMUNITY.

    PubMed

    Washington, Enrika; Weed, Latricia Diane; Vardaman, Shellye A

    2015-01-01

    Physical inactivity is the biggest public health problem of the 21st Century. Additionally, minority populations have higher rates of obesity and obesity-related illnesses, supporting the need to develop culturally-appropriate physical activity interventions for these populations. For African Americans (AAs), churches promote spiritual, mental, and physical well-being. The Internet offers an innovative medium to produce health behavior change and may be ideal to use with AAs in a church setting. A simple, no-cost, 8-week, Internet-delivered intervention to increase physical activity was piloted in an AA church. Level of activity increased, whereas time spent sitting decreased. PMID:26211303

  8. Successful Face Recognition is Associated with Increased Prefrontal Cortex Activation in Autism Spectrum Disorder

    PubMed Central

    Herrington, John D.; Riley, Meghan E.; Grupe, Daniel W.; Schultz, Robert T.

    2014-01-01

    This study examines whether deficits in visual information processing in ASD can be offset by the recruitment of brain structures involved in selective attention. During functional MRI, 12 children with ASD and 19 control participants completed a selective attention one-back task in which images of faces and houses were superimposed. When attending to faces, the ASD group showed increased activation relative to control participants within multiple prefrontal cortex areas, including dorsolateral prefrontal cortex (DLPFC). DLPFC activation in ASD was associated with increased response times for faces. These data suggest that prefrontal cortex activation may represent a compensatory mechanism for diminished visual information processing abilities. PMID:25234479

  9. p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin.

    PubMed

    Ehrnhoefer, Dagmar E; Skotte, Niels H; Ladha, Safia; Nguyen, Yen T N; Qiu, Xiaofan; Deng, Yu; Huynh, Khuong T; Engemann, Sabine; Nielsen, Signe M; Becanovic, Kristina; Leavitt, Blair R; Hasholt, Lis; Hayden, Michael R

    2014-02-01

    Activation of caspase-6 in the striatum of both presymptomatic and affected persons with Huntington's disease (HD) is an early event in the disease pathogenesis. However, little is known about the role of caspase-6 outside the central nervous system (CNS) and whether caspase activation might play a role in the peripheral phenotypes, such as muscle wasting observed in HD. We assessed skeletal muscle tissue from HD patients and well-characterized mouse models of HD. Cleavage of the caspase-6 specific substrate lamin A is significantly increased in skeletal muscle obtained from HD patients as well as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A. Using mouse embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-α (pifα), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53's mitochondrial pro-apoptotic function. Remarkably, the p53-mediated increase in caspase-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase-6. Furthermore, these results suggest that this pathway is activated both within and outside the CNS in HD and may contribute to both loss of CNS neurons and muscle atrophy. PMID:24070868

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

    PubMed

    Hannukainen, Jarna C; Nuutila, Pirjo; Borra, Ronald; 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 (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 micromol (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

  11. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  12. A-Ring Dihalogenation Increases the Cellular Activity of Combretastatin-Templated Tetrazoles

    PubMed Central

    2012-01-01

    The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (32–34), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G2/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity. PMID:24900453

  13. BrO/SO2 ratios at Popocatepetl volcano during increased activity in 2012

    NASA Astrophysics Data System (ADS)

    Fickel, M.; Delgado Granados, H.

    2012-12-01

    Since its reactivation in 1994 after many decades of inactivity, Popocatepetl volcano has been showing long periods of quiescent degassing and some events of intensified activity in connection with dome building and destruction processes. During a period of increased activity of the volcano, which began in April 2012, mobile ultraviolet DOAS measurements and stationary DOAS scans were performed to quantify SO2 fluxes and BrO/SO2 ratios within the volcanic plume. The results of these measurements are presented in the context of the volcanic activity, which consisted of increased emission of gas and ash and Vulcanian type explosions. In general, SO2 emissions were high during the period April-June 2012 and so the BrO emissions, however, the BrO/SO2 ratios did not change strongly before, during and after the increased activity.

  14. Cavity approximation for graphical models.

    PubMed

    Rizzo, T; Wemmenhove, B; Kappen, H J

    2007-07-01

    We reformulate the cavity approximation (CA), a class of algorithms recently introduced for improving the Bethe approximation estimates of marginals in graphical models. In our formulation, which allows for the treatment of multivalued variables, a further generalization to factor graphs with arbitrary order of interaction factors is explicitly carried out, and a message passing algorithm that implements the first order correction to the Bethe approximation is described. Furthermore, we investigate an implementation of the CA for pairwise interactions. In all cases considered we could confirm that CA[k] with increasing k provides a sequence of approximations of markedly increasing precision. Furthermore, in some cases we could also confirm the general expectation that the approximation of order k , whose computational complexity is O(N(k+1)) has an error that scales as 1/N(k+1) with the size of the system. We discuss the relation between this approach and some recent developments in the field. PMID:17677405

  15. Preliminary efficacy of prize-based contingency management to increase activity levels in healthy adults.

    PubMed

    Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L

    2014-01-01

    An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity. PMID:24740477

  16. Apocynin increases glutathione synthesis and activates AP-1 in alveolar epithelial cells.

    PubMed

    Lapperre, T S; Jimenez, L A; Antonicelli, F; Drost, E M; Hiemstra, P S; Stolk, J; MacNee, W; Rahman, I

    1999-01-25

    Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent intracellular inhibitor of superoxide anion production in neutrophils. In this study, we studied the effect of apocynin on the regulation of the antioxidant glutathione (GSH) and activation of the transcription factor AP-I in human alveolar epithelial cells (A549). Apocynin enhanced intracellular GSH by increasing gamma-glutamylcysteine synthetase activity in A549 cells. Apocynin also increased the expression of gamma-GCS heavy subunit mRNA. This was associated with increased AP-1 DNA binding as measured by the electrophoretic mobility shift assay. These data indicate that apocynin displays antioxidant properties, in part, by increasing glutathione synthesis through activation of AP-1. PMID:9989612

  17. Calpain activity and expression are increased in splenic inflammatory cells associated with experimental allergic encephalomyelitis.

    PubMed

    Shields, D C; Schaecher, K E; Goust, J M; Banik, N L

    1999-09-01

    Since calcium-activated neutral proteinase (calpain) activity and expression are significantly increased in activated glial/inflammatory cells in the central nervous system of animals with autoimmune demyelinating diseases, this enzyme may also play a role in peripheral organ systems in these diseases. In this study, the activity and expression of calpain and the endogenous inhibitor, calpastatin, were evaluated at transcriptional and translational levels in spleens of Lewis rats with acute experimental allergic encephalomyelitis (EAE) prior to the onset of clinical symptoms. Calpain activity and translational expression were increased by 475.5% and 44.3% respectively, on day 4 post-induction in adjuvant controls and animals with EAE. These levels remained elevated compared to normal controls on days 8 and 12. Calpastatin translational expression was similarly increased at these time points although transcriptional expression was not significantly altered at any time following induction of EAE. Likewise, transcriptional expression of mu-calpain was unchanged following induction, while small increases in m-calpain transcriptional expression were observed on days 2 and 8. Most calpain expression was observed in activated splenic macrophages at day 8 post-induction even though activated T cells were also calpain positive. In spinal cords of animals with EAE, calpain expression was significantly increased in rats with severe disease compared to those exhibiting only mild symptoms at day 12 post-induction. Thus, prior to symptomatic EAE, increased calpain activity and expression in peripheral lymphoid organs may play an important role in T cell migration and subsequent disease progression. PMID:10496171

  18. Increase of rutin antioxidant activity by generating Maillard reaction products with lysine.

    PubMed

    Zhang, Ru; Zhang, Bian-Ling; He, Ting; Yi, Ting; Yang, Ji-Ping; He, Bin

    2016-06-01

    Rutin exists in medicinal herbs, fruits, vegetables, and a number of plant-derived sources. Dietary sources containing rutin are considered beneficial because of their potential protective roles in multiple diseases related to oxidative stresses. In the present study, the change and antioxidation activity of rutin in Maillard reaction with lysine through a heating process were investigated. There is release of glucose and rhamnose that interact with lysine to give Maillard reaction products (MRPs), while rutin is converted to less-polar quercetin and a small quantity of isoquercitrin. Because of their high cell-membrane permeability, the rutin-lysine MRPs increase the free radical-scavenging activity in HepG2 cells, showing cellular antioxidant activity against Cu(2+)-induced oxidative stress higher than that of rutin. Furthermore, the MRPs significantly increased the Cu/Zn SOD (superoxide dismutase) activity and Cu/Zn SOD gene expression of HepG2 cells, consequently enhancing antioxidation activity. PMID:27106712

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

    PubMed

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

    2011-10-14

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

  20. Indirect aluminum toxicity to the green alga Scenedesmus through increased cupric ion activity

    SciTech Connect

    Rueter, J.G. Jr.; O'Reilly, K.T.; Petersen, R.R.

    1987-05-01

    Additions of aluminum and copper to chemically defined media resulted in inhibition of growth of Scenedesmus and of alkaline phosphatase activity. The alkaline phosphatase activity was assayed both on commercially available purified enzyme from bacteria and on the enzyme present in whole Scenedesmus cells. The effect of metal additions was compared to the total aluminum added and to the computed free ion activities for both copper and aluminum. In all three systems (algal growth, purified enzyme, and algal enzyme) the observed toxicity with increased total aluminum was mostly due to an increase in cupric ion activity. The algal growth response was affected for the range of cupric ion activities from 10/sup -6/ to 10/sup -12/. The toxic dose response of aluminum was largely due to indirect competitive effects of Al in the medium that displaced copper from the chelator. 33 references, 4 figures.

  1. Plasma cathepsin D isoforms and their active metabolites increase after myocardial infarction and contribute to plasma renin activity.

    PubMed

    Naseem, R Haris; Hedegard, Wade; Henry, Timothy D; Lessard, Jennifer; Sutter, Kathryn; Katz, Stephen A

    2005-03-01

    Plasma renin activity (PRA) is often found to increase after myocardial infarction (MI). Elevated PRA may contribute to increased myocardial angiotensin II that is responsible for maladaptive remodeling of the myocardium after MI. We hypothesized that MI would also result in cardiac release of cathepsin D, a ubiquitous lysosomal enzyme with high renin sequence homology. Cathepsin D release from damaged myocardial tissue could contribute to angiotensin formation by acting as an enzymatic alternate to renin. We assessed circulating renin and cathepsin D from both control and MI patient plasma (7-20 hours after MI) using shallow gradient focusing that allowed for independent measurement of both enzymes. Cathepsin D was increased significantly in the plasma after MI (P < 0.001). Furthermore, circulating active cathepsin D metabolites were also significantly elevated after MI (P < 0.04), and contained the majority of cathepsin D activity in plasma. Spiking control plasma with cathepsin D resulted in a variable but significant (P = 0.005) increase in PRA using a clinical assay. We conclude that 7-20 hours after MI, plasma cathepsin D is significantly elevated and most of the active enzymatic activity is circulating as plasma metabolites. Circulating cathepsin D can falsely increase clinical PRA determinations, and may also provide an alternative angiotensin formation pathway after MI. PMID:15739123

  2. Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity

    PubMed Central

    Vijgen, Guy H. E. J.; Bouvy, Nicole D.; Leenen, Loes; Rijkers, Kim; Cornips, Erwin; Majoie, Marian; Brans, Boudewijn; van Marken Lichtenbelt, Wouter D.

    2013-01-01

    Background Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. Methods and Findings Fifteen patients with stable VNS therapy (age: 45±10yrs; body mass index; 25.2±3.5 kg/m2) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUVMean; 0.55±0.25 versus 0.67±0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001). Conclusions VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. Trial Registration The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282. PMID:24194874

  3. Neuromedin U in the paraventricular and arcuate hypothalamic nuclei increases non-exercise activity thermogenesis.

    PubMed

    Novak, C M; Zhang, M; Levine, J A

    2006-08-01

    Brain neuromedin U (NMU) has been associated with the regulation of both energy intake and expenditure. We hypothesized that NMU induces changes in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) through its actions on hypothalamic nuclei. We applied increasing doses of NMU directly to the paraventricular (PVN) and arcuate hypothalamic nuclei using chronic unilateral guide cannulae. In both nuclei, NMU significantly and dose-dependently increased physical activity and NEAT. Moreover, NMU increased physical activity and NEAT during the first hour of the dark phase, indicating that the reduction of sleep is unlikely to account for the increased physical activity seen with NMU treatment. As a positive control, we demonstrated that paraventricular NMU also significantly decreased food intake, as well as body weight. These data demonstrate that NMU is positively associated with NEAT through its actions in the PVN and arcuate nucleus. In co-ordination with its suppressive effects on feeding, the NEAT-activating effects of NMU make it a potential candidate in the combat of obesity. PMID:16867180

  4. Increased cell proliferation and neural activity by physostigmine in the telencephalon of adult zebrafish.

    PubMed

    Lee, Yunkyoung; Lee, Bongkyu; Jeong, Sumin; Park, Ji-Won; Han, Inn-Oc; Lee, Chang-Joong

    2016-08-26

    Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU-labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200μM physostigmine, which was inhibited by pretreatment with 200μM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200μM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30min treatment with 200μM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200μM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20μM physostigmine. These results suggest that 200μM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish. PMID:27378362

  5. Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women.

    PubMed

    Gregory, Rebecca; Cheng, Hu; Rupp, Heather A; Sengelaub, Dale R; Heiman, Julia R

    2015-03-01

    After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother-infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual

  6. Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women

    PubMed Central

    Gregory, Rebecca; Cheng, Hu; Rupp, Heather A.; Sengelaub, Dale R.; Heiman, Julia R.

    2015-01-01

    After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother–infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual

  7. Flaking process increases the NF-κB inhibition activity and melanoidin extractability of coffee.

    PubMed

    Chu, Yi-Fang; Hu, Kang; Hatzold, Thomas; Black, Richard M; Chen, Don

    2013-09-01

    Research on the health impacts of coffee has escalated. However, few studies were devoted to understanding the potential impact of mechanical processing on coffee's chemistry and subsequent health implications. Coffee flaking is a commonly used process to improve extractability and aroma characteristics. In this study, we studied the biochemical activity, chemical composition, and microstructure of coffee before and after flaking. We found that flaked coffee extract had 3.3-fold higher activity in inhibiting nuclear factor-kappa B (NF-κB) activation than regular coffee extract. Interestingly, flaking did not significantly alter the amount of coffee phenolics. It increased coffee melanoidin, by 2.1-fold, which likely contributed to the observed higher activity in inhibiting NF-κB activation. Flaking crushed cell walls revealed by microscopy might possibly result in disruption of polysaccharide entanglement and release of high-molecular-weight compounds, such as melanoidins. Consequently, the increased melanoidin content in the brew resulted in the increased inhibition of NF-κB activation. Small molecules, like coffee phenolics, are readily soluble in water during coffee brewing even without flaking, suggesting that flaking has no effect on its extractability. In summary, our investigation revealed that flaking enhanced NF-κB inhibition activity, possibly through the release of melanoidins from crushed cell microstructures. PMID:24804042

  8. Flaking process increases the NF-κB inhibition activity and melanoidin extractability of coffee

    PubMed Central

    Chu, Yi-Fang; Hu, Kang; Hatzold, Thomas; Black, Richard M; Chen, Don

    2013-01-01

    Research on the health impacts of coffee has escalated. However, few studies were devoted to understanding the potential impact of mechanical processing on coffee's chemistry and subsequent health implications. Coffee flaking is a commonly used process to improve extractability and aroma characteristics. In this study, we studied the biochemical activity, chemical composition, and microstructure of coffee before and after flaking. We found that flaked coffee extract had 3.3-fold higher activity in inhibiting nuclear factor-kappa B (NF-κB) activation than regular coffee extract. Interestingly, flaking did not significantly alter the amount of coffee phenolics. It increased coffee melanoidin, by 2.1-fold, which likely contributed to the observed higher activity in inhibiting NF-κB activation. Flaking crushed cell walls revealed by microscopy might possibly result in disruption of polysaccharide entanglement and release of high-molecular-weight compounds, such as melanoidins. Consequently, the increased melanoidin content in the brew resulted in the increased inhibition of NF-κB activation. Small molecules, like coffee phenolics, are readily soluble in water during coffee brewing even without flaking, suggesting that flaking has no effect on its extractability. In summary, our investigation revealed that flaking enhanced NF-κB inhibition activity, possibly through the release of melanoidins from crushed cell microstructures. PMID:24804042

  9. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC

    SciTech Connect

    Murakami, Hisashi; Murakami, Ryuichiro . E-mail: ryuichi@med.nagoya-u.ac.jp; Kambe, Fukushi; Cao, Xia; Takahashi, Ryotaro; Asai, Toru; Hirai, Toshihisa; Numaguchi, Yasushi; Okumura, Kenji; Seo, Hisao; Murohara, Toyoaki

    2006-03-24

    Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor {alpha}.

  10. Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients.

    PubMed

    Enooku, Kenichiro; Nakagawa, Hayato; Soroida, Yoko; Ohkawa, Ryunosuke; Kageyama, Yuko; Uranbileg, Baasanjav; Watanabe, Naoko; Tateishi, Ryosuke; Yoshida, Haruhiko; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-08-15

    Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of ≤ 9.0 U/L even in patients with elevated liver stiffness value, >15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients. PMID:24420733

  11. Daily intake of Lactobacillus casei Shirota increases natural killer cell activity in smokers.

    PubMed

    Reale, Marcella; Boscolo, Paolo; Bellante, Veronica; Tarantelli, Chiara; Di Nicola, Marta; Forcella, Laura; Li, Qing; Morimoto, Kanehisa; Muraro, Raffaella

    2012-07-01

    Dietary probiotics supplementation exerts beneficial health effects. Since cigarette smoking reduces natural killer (NK) activity, we evaluated the effect of Lactobacillus casei Shirota (LcS) intake on NK cytotoxic activity in male smokers. The double-blind, placebo-controlled, randomised study was conducted on seventy-two healthy Italian blue-collar male smokers randomly divided for daily intake of LcS powder or placebo. Before and after 3 weeks of intake, peripheral blood mononuclear cells were isolated and NK activity and CD16⁺ cells' number were assessed. Daily LcS intake for 3 weeks significantly increased NK activity (P < 0.001). The increase in NK activity was paralleled by an increase in CD16⁺ cells (P < 0.001). Before intake, NK cytotoxic activity inversely correlated with the number of cigarettes smoked (R - 0.064). LcS intake prevented the smoke-dependent expected NK activity reduction. The analysis of the distribution of changes in smoke-adjusted NK activity demonstrated that the positive variations were significantly associated with LcS intake, while the negative variations were associated with placebo intake (median value of distributions of differences, 20.98 lytic unit (LU)/10⁷ cells for LcS v. - 4.38 LU/10⁷ cells for placebo, P = 0.039). In conclusion, 3 weeks of daily LcS intake in Italian male smokers was associated with a higher increase in cytotoxic activity and CD16⁺ cells' number in comparison to the placebo intake group. PMID:22142891

  12. Dietary resveratrol administration increases MnSOD expression and activity in mouse brain

    SciTech Connect

    Robb, Ellen L.; Winkelmolen, Lieke; Visanji, Naomi; Brotchie, Jonathan; Stuart, Jeffrey A.

    2008-07-18

    trans-Resveratrol (3,4',5-trihydroxystilbene; RES) is of interest for its reported protective effects in a variety of pathologies, including neurodegeneration. Many of these protective properties have been attributed to the ability of RES to reduce oxidative stress. In vitro studies have shown an increase in antioxidant enzyme activities following exposure to RES, including upregulation of mitochondrial superoxide dismutase, an enzyme that is capable of reducing both oxidative stress and cell death. We sought to determine if a similar increase in endogenous antioxidant enzymes is observed with RES treatment in vivo. Three separate modes of RES delivery were utilized; in a standard diet, a high fat diet and through a subcutaneous osmotic minipump. RES given in a high fat diet proved to be effective in elevating antioxidant capacity in brain resulting in an increase in both MnSOD protein level (140%) and activity (75%). The increase in MnSOD was not due to a substantial proliferation of mitochondria, as RES treatment induced a 10% increase in mitochondrial abundance (Citrate Synthase activity). The potential neuroprotective properties of MnSOD have been well established, and we demonstrate that a dietary delivery of RES is able to increase the expression and activity of this enzyme in vivo.

  13. Methylglyoxal increases cardiomyocyte ischemia-reperfusion injury via glycative inhibition of thioredoxin activity

    PubMed Central

    Wang, Xiao-Liang; Lau, Wayne B.; Yuan, Yue-Xing; Wang, Ya-Jing; Yi, Wei; Christopher, Theodore A.; Lopez, Bernard L.; Liu, Hui-Rong

    2010-01-01

    Diabetes mellitus (DM) is closely related to cardiovascular morbidity and mortality, but the specific molecular basis linking DM with increased vulnerability to cardiovascular injury remains incompletely understood. Methylglyoxal (MG), a precursor to advanced glycation end products (AGEs), is increased in diabetic patient plasma, but its role in diabetic cardiovascular complications is unclear. Thioredoxin (Trx), a cytoprotective molecule with antiapoptotic function, has been demonstrated to be vulnerable to glycative inhibition, but whether Trx is glycatively inhibited by MG, thus contributing to increased cardiac injury, has never been investigated. Cultured H9c2 cardiomyocytes were treated with MG (200 μM) for 6 days. The following were determined pre- and post-simulated ischemia-reperfusion (SI-R; 8 h of hypoxia followed by 3 h of reoxygenation): cardiomyocyte death/apoptosis, Trx expression and activity, AGE formation, Trx-apoptosis-regulating kinase-1 (Trx-ASK1) complex formation, and p38 mitogen-activated protein kinase (MAPK) phosphorylation and activity. Compared with vehicle, MG significantly increased SI-R-induced cardiomyocyte LDH release and apoptosis (P < 0.01). Prior to SI-R, Trx activity was reduced in MG-treated cells, but Trx expression was increased moderately. Moreover, Trx-ASK1 complex formation was reduced, and both p38 MAPK activity and phosphorylation were increased. To investigate the effects of MG on Trx directly, recombinant human Trx (hTrx) was incubated with MG in vitro. Compared with vehicle, MG incubation markedly increased CML formation (a glycation footprint) and inhibited Trx activity. Finally, glycation inhibitor aminoguanidine administration during MG treatment of cultured cells reduced AGE formation, increased Trx activity, restored Trx-ASK1 interaction, and reduced p38 MAPK phosphorylation and activity, caspase-3 activation, and LDH release (P < 0.01). We demonstrated for the first time that methylglyoxal sensitized cultured

  14. 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

  15. Curcumin increases gelatinase activity in human neutrophils by a p38 mitogen-activated protein kinase (MAPK)-independent mechanism.

    PubMed

    Antoine, Francis; Girard, Denis

    2015-01-01

    Curcumin has been found to possess anti-inflammatory activities and neutrophils, key players in inflammation, were previously found to be important targets to curcumin in a few studies. For example, curcumin was found to induce apoptosis in neutrophils by a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism. However, the role of curcumin on the biology of neutrophils is still poorly defined. To study the role of curcumin on neutrophil degranulation and to determine the role of p38 MAPK, human neutrophils were freshly isolated from healthy individuals and incubated in vitro with curcumin. Degranulation was studied at three levels: surface expression of granule markers by flow cytometry; release of matrix metallopeptidase-9 (MMP-9 or gelatinase B) enzyme into supernatants by Western blot; and gelatinase B activity by zymography. Activation of p38 MAPK was studied by monitoring its tyrosine phosphorylation levels by western blot and its role by the utilization of a pharmacological inhibitor. The results indicate that curcumin increased the cell surface expression of CD35 (secretory vesicle), CD63 (azurophilic granules), and CD66b (gelatinase granules) in neutrophils. Also, curcumin increased the release and enzymatic activity of gelatinase B in the extracellular milieu and activated p38 MAP kinase in these cells. However, in contrast to fMLP, curcumin-induced enzymatic activity and secretion of gelatinase B were not reversed by use of a p38 inhibitor. Finally, it was found that curcumin was able to enhance phagocytosis. Taken together, the results here demonstrate that curcumin induced degranulation in human neutrophils and that the increased gelatinase activity is not dependent on p38 MAPK activation. Therefore, degranulation is another human neutrophil function that could be modulated by curcumin, as well as phagocytosis. PMID:24926560

  16. Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity

    PubMed Central

    Trivedi, Palak J.; Bruns, Tony; Ward, Stephen; Mai, Martina; Schmidt, Carsten; Hirschfield, Gideon M.; Weston, Chris J.; Adams, David H.

    2016-01-01

    CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4+) and 30% (CD8+) of tissue-infiltrating T-cells in colitis were identified as CCR9+ effector lymphocytes, compared to <10% of T-cells being CCR9+ in normal colon. Sorted CCR9+ lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9– counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver. PMID:26873648

  17. Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity.

    PubMed

    Trivedi, Palak J; Bruns, Tony; Ward, Stephen; Mai, Martina; Schmidt, Carsten; Hirschfield, Gideon M; Weston, Chris J; Adams, David H

    2016-04-01

    CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4(+)) and 30% (CD8(+)) of tissue-infiltrating T-cells in colitis were identified as CCR9(+) effector lymphocytes, compared to <10% of T-cells being CCR9(+) in normal colon. Sorted CCR9(+) lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9(-) counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver. PMID:26873648

  18. Selective Estrogen Receptor Modulation Increases Hippocampal Activity during Probabilistic Association Learning in Schizophrenia

    PubMed Central

    Kindler, Jochen; Weickert, Cynthia Shannon; Skilleter, Ashley J; Catts, Stanley V; Lenroot, Rhoshel; Weickert, Thomas W

    2015-01-01

    People with schizophrenia show probabilistic association learning impairment in conjunction with abnormal neural activity. The selective estrogen receptor modulator (SERM) raloxifene preserves neural activity during memory in healthy older men and improves memory in schizophrenia. Here, we tested the extent to which raloxifene modifies neural activity during learning in schizophrenia. Nineteen people with schizophrenia participated in a twelve-week randomized, double-blind, placebo-controlled, cross-over adjunctive treatment trial of the SERM raloxifene administered orally at 120 mg daily to assess brain activity during probabilistic association learning using functional magnetic resonance imaging (fMRI). Raloxifene improved probabilistic association learning and significantly increased fMRI BOLD activity in the hippocampus and parahippocampal gyrus relative to placebo. A separate region of interest confirmatory analysis in 21 patients vs 36 healthy controls showed a positive association between parahippocampal neural activity and learning in patients, but no such relationship in the parahippocampal gyrus of healthy controls. Thus, selective estrogen receptor modulation by raloxifene concurrently increases activity in the parahippocampal gyrus and improves probabilistic association learning in schizophrenia. These results support a role for estrogen receptor modulation of mesial temporal lobe neural activity in the remediation of learning disabilities in both men and women with schizophrenia. PMID:25829142

  19. Increased Capillary Endothelial Cell Protease Activity in Response to Angiogenic Stimuli in vitro

    NASA Astrophysics Data System (ADS)

    Gross, Janet L.; Moscatelli, David; Rifkin, Daniel B.

    1983-05-01

    Bovine capillary endothelial (BCE) cells produce increased amounts of the proteases plasminogen activator (PA) and latent collagenase when cultured in the presence of the following preparations which are known to contain angiogenic activities: bovine retinal extract, mouse adipocyte conditioned medium, and human hepatoma cell lysate. These preparations stimulated both BCE cell PA and collagenase activities in a dose-dependent manner. Both activities were increased to about the same level by these preparations as by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. Mitogens that are not angiogenic, such as insulin, epidermal and fibroblast growth factors, and endothelial cell growth supplement, had no effect on BCE cell PA and collagenase activities. Two of the angiogenic preparations (retinal extract and mouse adipocyte-conditioned medium) had no effect on PA activity in endothelial cells derived from bovine aortae (BAE cells). The angiogenic preparations had little (human hepatoma cell lysate, mouse adipocyte-conditioned medium) or no (bovine retinal extract) effect on BAE cell collagenase activities. In the bovine system, the induction of high levels of both PA and collagenase activities by angiogenic preparations is limited to capillary endothelial cells.

  20. Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells

    SciTech Connect

    Wu, Juanjuan; Williams, Devin; Walter, Grant A.; Thompson, Winston E.; Sidell, Neil

    2014-11-01

    The actions of the transcription factor Nuclear factor erythroid 2-related factor (Nrf2) in breast cancer have been shown to include both pro-oncogenic and anti-oncogenic activities which is influenced, at least in part, by the hormonal environment. However, direct regulation of Nrf2 by steroid hormones (estrogen and progesterone) has received only scant attention. Nrf2 is known to be regulated by its cytosolic binding protein, Kelch-like ECH-associated protein 1 (Keap1), and by a Keap1-independent mechanism involving a series of phosphorylation steps mediated by phosphatidylinositol 3-kinase (PI3K) and glycogen synthase kinase 3 beta (GSK3β). Here, we report that estrogen (E2) increases Nrf2 activity in MCF7 breast cancer cells through activation of the PI3K/GSK3β pathway. Utilizing antioxidant response element (ARE)-containing luciferase reporter constructs as read-outs for Nrf2 activity, our data indicated that E2 increased ARE activity >14-fold and enhanced the action of the Nrf2 activators, tertiary butylhydroquinone (tBHQ) and sulforaphane (Sul) 4 to 9 fold compared with cells treated with tBHQ or Sul as single agents. This activity was shown to be an estrogen receptor-mediated phenomenon and was antagonized by progesterone. In addition to its action on the reporter constructs, mRNA and protein levels of heme oxygenase 1, an endogenous target gene of Nrf2, was markedly upregulated by E2 both alone and in combination with tBHQ. Importantly, E2-induced Nrf2 activation was completely suppressed by the PI3K inhibitors LY294002 and Wortmannin while the GSK3β inhibitor CT99021 upregulated Nrf2 activity. Confirmation that E2 was, at least partly, acting through the PI3K/GSK3β pathway was indicated by our finding that E2 increased the phosphorylation status of both GSK3β and Akt, a well-characterized downstream target of PI3K. Together, these results demonstrate a novel mechanism by which E2 can regulate Nrf2 activity in estrogen receptor-positive breast cancer

  1. The activity of seminal creatine kinase is increased in the presence of pentoxifylline.

    PubMed

    Banihani, S A; Abu-Alhayjaa, R F

    2016-06-01

    Creatine kinase enzyme (CK) is indispensable for sperm function because it catalyses the regeneration of ATP from the chemical shuttle between creatine and creatine phosphate. Here, we measured CK activity of human spermatozoa in the presence of pentoxifylline (PF), a xanthine derivative drug primarily used to treat peripheral vascular function. Nine semen samples from different males were subjected to swim up, incubated with PF and tested for CK activity using the kinetic spectrophotometric method. The CK activity of spermatozoa significantly increased after addition of PF at 5 mm compared with the control (with 0.0 mm PF). Given that PF has been identified as a sperm motility enhancer and that CK is crucial for adequate sperm motion; then, the aptitude of PF to enhance sperm motility may be modulated by increasing CK activity. PMID:26395279

  2. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    PubMed Central

    Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude

    2016-01-01

    Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187

  3. Approximate flavor symmetries

    SciTech Connect

    Rasin, A.

    1994-04-01

    We discuss the idea of approximate flavor symmetries. Relations between approximate flavor symmetries and natural flavor conservation and democracy models is explored. Implications for neutrino physics are also discussed.

  4. Carbon-Degrading Enzyme Activities Stimulated by Increased Nutrient Availability in Arctic Tundra Soils

    PubMed Central

    Koyama, Akihiro; Wallenstein, Matthew D.; Simpson, Rodney T.; Moore, John C.

    2013-01-01

    Climate-induced warming of the Arctic tundra is expected to increase nutrient availability to soil microbes, which in turn may accelerate soil organic matter (SOM) decomposition. We increased nutrient availability via fertilization to investigate the microbial response via soil enzyme activities. Specifically, we measured potential activities of seven enzymes at four temperatures in three soil profiles (organic, organic/mineral interface, and mineral) from untreated native soils and from soils which had been fertilized with nitrogen (N) and phosphorus (P) since 1989 (23 years) and 2006 (six years). Fertilized plots within the 1989 site received annual additions of 10 g N⋅m-2⋅year-1 and 5 g P⋅m-2⋅year-1. Within the 2006 site, two fertilizer regimes were established – one in which plots received 5 g N⋅m-2⋅year-1 and 2.5 g P⋅m-2⋅year-1 and one in which plots received 10 g N⋅m-2⋅year-1 and 5 g P⋅m-2⋅year-1. The fertilization treatments increased activities of enzymes hydrolyzing carbon (C)-rich compounds but decreased phosphatase activities, especially in the organic soils. Activities of two enzymes that degrade N-rich compounds were not affected by the fertilization treatments. The fertilization treatments increased ratios of enzyme activities degrading C-rich compounds to those for N-rich compounds or phosphate, which could lead to changes in SOM chemistry over the long term and to losses of soil C. Accelerated SOM decomposition caused by increased nutrient availability could significantly offset predicted increased C fixation via stimulated net primary productivity in Arctic tundra ecosystems. PMID:24204773

  5. Carbon-degrading enzyme activities stimulated by increased nutrient availability in Arctic tundra soils.

    PubMed

    Koyama, Akihiro; Wallenstein, Matthew D; Simpson, Rodney T; Moore, John C

    2013-01-01

    Climate-induced warming of the Arctic tundra is expected to increase nutrient availability to soil microbes, which in turn may accelerate soil organic matter (SOM) decomposition. We increased nutrient availability via fertilization to investigate the microbial response via soil enzyme activities. Specifically, we measured potential activities of seven enzymes at four temperatures in three soil profiles (organic, organic/mineral interface, and mineral) from untreated native soils and from soils which had been fertilized with nitrogen (N) and phosphorus (P) since 1989 (23 years) and 2006 (six years). Fertilized plots within the 1989 site received annual additions of 10 g N · m(-2) · year(-1) and 5 g P · m(-2) · year(-1). Within the 2006 site, two fertilizer regimes were established--one in which plots received 5 g N · m(-2) · year(-1) and 2.5 g P · m(-2) · year(-1) and one in which plots received 10 g N · m(-2) · year(-1) and 5 g P · m(-2) · year(-1). The fertilization treatments increased activities of enzymes hydrolyzing carbon (C)-rich compounds but decreased phosphatase activities, especially in the organic soils. Activities of two enzymes that degrade N-rich compounds were not affected by the fertilization treatments. The fertilization treatments increased ratios of enzyme activities degrading C-rich compounds to those for N-rich compounds or phosphate, which could lead to changes in SOM chemistry over the long term and to losses of soil C. Accelerated SOM decomposition caused by increased nutrient availability could significantly offset predicted increased C fixation via stimulated net primary productivity in Arctic tundra ecosystems. PMID:24204773

  6. Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

    PubMed Central

    Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

    2012-01-01

    Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor. PMID:23203056

  7. Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor.

    PubMed

    Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L; Minassian, Arpi

    2016-06-30

    Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses. Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature. PMID:27138818

  8. Texting to Increase Physical Activity Among Teenagers (TXT Me!): Rationale, Design, and Methods Proposal

    PubMed Central

    Cantu, Dora; Bhatt, Riddhi; Baranowski, Tom; Rodgers, Wendy; Jago, Russell; Anderson, Barbara; Liu, Yan; Mendoza, Jason A; Tapia, Ramsey; Buday, Richard

    2014-01-01

    Background Physical activity decreases from childhood through adulthood. Among youth, teenagers (teens) achieve the lowest levels of physical activity, and high school age youth are particularly at risk of inactivity. Effective methods are needed to increase youth physical activity in a way that can be maintained through adulthood. Because teens text a great deal, text messages promoting walking, a low cost physical activity, may be an effective method for promoting sustainable physical activity. Objective The objective of our study was to determine the effect of pedometers, self selected step goals, and texts grounded in the self-determination theory (SDT) on physical activity among the teens. Methods “TXT Me!” was a 12 week intervention that texted 14-17 year olds to increase their daily physical activity by increasing the number of steps they take each day. The intervention was grounded in the SDT. Formative research with the teens helped construct the intervention and develop the texts. A total of 84 texts were developed (12 to set a step goal, and 72 promoting autonomy, competence, and relatedness). The pilot evaluation used a four group, randomized design (n=160). After baseline data collection, the participants were randomized to one of four conditions (no treatment control, pedometer only, pedometer + weekly prompts, pedometer + weekly prompts + SDT grounded texts). Data were collected at baseline and immediately upon completion of the study. The primary outcome was physical activity, measured by 7 days of accelerometry. Basic psychological needs, physical activity motivation, process evaluation, and program satisfaction data were also collected. Results To our knowledge, this is one of the first studies to explore the use of stand alone, SDT grounded texts, supported by pedometers and prompts to set a self selected step goal, as a method for increasing physical activity among teens. Conclusions This pilot study will contribute valuable information

  9. ACROLEIN ACTIVATES MATRIX METALLOPROTEINASES BY INCREASING REACTIVE OXYGEN SPECIES IN MACROPHAGES

    PubMed Central

    O’Toole, Timothy E.; Zheng, Yu-Ting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-01-01

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca2+]i), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca2+]I with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca2+]I, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure. PMID:19371603

  10. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages.

    PubMed

    O'Toole, Timothy E; Zheng, Yu-Ting; Hellmann, Jason; Conklin, Daniel J; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca2+](i)), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca2+](I) with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca2+](I), leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure. PMID:19371603

  11. Less precise motor control leads to increased agonist-antagonist muscle activation during stick balancing.

    PubMed

    Reeves, N Peter; Popovich, John M; Vijayanagar, Vilok; Pathak, Pramod K

    2016-06-01

    Human motor control has constraints in terms of its responsiveness, which limit its ability to successfully perform tasks. In a previous study, it was shown that the ability to balance an upright stick became progressively more challenging as the natural frequency (angular velocity without control) of the stick increased. Furthermore, forearm and trunk agonist and antagonist muscle activation increased as the natural frequency of the stick increased, providing evidence that the central nervous system produces agonist-antagonist muscle activation to match task dynamics. In the present study, visual feedback of the stick position was influenced by changing where subject focused on the stick during stick balancing. It was hypothesized that a lower focal height would degrade motor control (more uncertainty in tracking stick position), thus making balancing more challenging. The probability of successfully balancing the stick at four different focal heights was determined along with the average angular velocity of the stick. Electromyographic signals from forearm and trunk muscles were also recorded. As expected, the probability of successfully balancing the stick decreased and the average angular velocity of the stick increased as subjects focused lower on the stick. In addition, changes in the level of agonist and antagonist muscle activation in the forearm and trunk was linearly related to changes in the angular velocity of the stick during balancing. One possible explanation for this is that the central nervous system increases muscle activation to account for less precise motor control, possibly to improve the responsiveness of human motor control. PMID:27010497

  12. Brain-derived neurotrophic factor rapidly increases NMDA receptor channel activity through Fyn-mediated phosphorylation.

    PubMed

    Xu, Fei; Plummer, Mark R; Len, Guo-Wei; Nakazawa, Takanobu; Yamamoto, Tadashi; Black, Ira B; Wu, Kuo

    2006-11-22

    Brain-derived neurotrophic factor (BDNF) is a potent modulator of hippocampal synaptic plasticity. Previously, we found that one of the targets of BDNF modulation is NR2B-containing NMDA receptors. Furthermore, exposure to the trophin rapidly increases NMDA receptor activity and enhances tyrosine phosphorylation of NR2B in cortical and hippocampal postsynaptic densities (PSDs), potentially linking receptor phosphorylation to synaptic plasticity. To define the specific NR2B residue(s) regulated by BDNF, we focused on tyrosine 1472, phosphorylation of which increases after LTP. BDNF rapidly increased phosphorylation in cortical PSDs. The tyrosine kinase Fyn is critical since BDNF-dependent phosphorylation was abolished in Fyn knockout mice. Single-channel patch clamp recordings showed that Fyn is required for the increase in NMDA receptor activity elicited by BDNF. Collectively, our results suggest that BDNF enhances phosphorylation of NR2B tyrosine 1472 through activation of Fyn, leading to alteration of NMDA receptor activity and increased synaptic transmission. PMID:17045972

  13. Estimating nonnegative matrix model activations with deep neural networks to increase perceptual speech quality.

    PubMed

    Williamson, Donald S; Wang, Yuxuan; Wang, DeLiang

    2015-09-01

    As a means of speech separation, time-frequency masking applies a gain function to the time-frequency representation of noisy speech. On the other hand, nonnegative matrix factorization (NMF) addresses separation by linearly combining basis vectors from speech and noise models to approximate noisy speech. This paper presents an approach for improving the perceptual quality of speech separated from background noise at low signal-to-noise ratios. An ideal ratio mask is estimated, which separates speech from noise with reasonable sound quality. A deep neural network then approximates clean speech by estimating activation weights from the ratio-masked speech, where the weights linearly combine elements from a NMF speech model. Systematic comparisons using objective metrics, including the perceptual evaluation of speech quality, show that the proposed algorithm achieves higher speech quality than related masking and NMF methods. In addition, a listening test was performed and its results show that the output of the proposed algorithm is preferred over the comparison systems in terms of speech quality. PMID:26428778

  14. Let's Move for Pacific Islander Communities: an Evidence-Based Intervention to Increase Physical Activity.

    PubMed

    LaBreche, Mandy; Cheri, Ashley; Custodio, Harold; Fex, Cleo Carlos; Foo, Mary Anne; Lepule, Jonathan Tana; May, Vanessa Tui'one; Orne, Annette; Pang, Jane Ka'ala; Pang, Victor Kaiwi; Sablan-Santos, Lola; Schmidt-Vaivao, Dorothy; Surani, Zul; Talavou, Melevesi Fifita; Toilolo, Tupou; Palmer, Paula Healani; Tanjasiri, Sora Park

    2016-06-01

    Pacific Islander (PI) populations of Southern California experience high obesity and low physical activity levels. Given PI's rich cultural ties, efforts to increase physical activity using a community-tailored strategy may motivate members in a more sustainable manner. In this paper, we (1) detail the program adaptation methodology that was utilized to develop the Weaving an Islander Network for Cancer Awareness, Research and Training (WINCART) Center's PI Let's Move Program, a culturally tailored program aimed to increase physical activity levels among members of PI organizations in Southern California, and (2) share the program's pilot evaluation results on individual and organizational changes. The WINCART Center applied the National Cancer Institute's program adaptation guidelines to tailor the evidence-based Instant Recess program to fit the needs of PIs. The end product, the PI Let's Move Program, was piloted in 2012 with eight PI organizations, reaching 106 PI adults. At baseline, 52 % of participants reported that they were not physically active, with the average number of days engaged in medium-intensity physical activity at 2.09 days/week. After the 2-month program, participants increased the number of days that they engaged in medium-intensity physical activity from 2.09 to 2.90 days/week. Post-pilot results found that 82 % of participants reported intentions to engage in physical activity for at least the next 6 months. At baseline, only one organization was currently implementing a physical activity program, and none had implemented an evidence-based physical activity program tailored for PIs. After the 2-month timeframe, despite varying levels of capacity, all eight organizations were able to successfully implement the program. In conclusion, results from our program provide evidence that disparity populations, such as PIs, can be successfully reached through programs that are culturally tailored to both individuals and their community

  15. Spirulina elicits the activation of innate immunity and increases resistance against Vibrio alginolyticus in shrimp.

    PubMed

    Chen, Yu-Yuan; Chen, Jiann-Chu; Tayag, Carina Miranda; Li, Hui-Fang; Putra, Dedi Fazriansyah; Kuo, Yi-Hsuan; Bai, Jia-Chin; Chang, Yu-Hsuan

    2016-08-01

    The effect of Spirulina dried powder (SDP) on the immune response of white shrimp Litopenaeus vannamei was studied in vitro and in vivo. Incubating shrimp haemocytes in 0.5 mg ml(-1) SDP caused the degranulation of haemocytes and a reduction in the percentage of large cells within 30 min. Shrimp haemocytes incubated in 1 mg ml(-1) SDP significantly increased their phenoloxidase (PO) activity, serine proteinase activity, and respiratory burst activity (RB, release of superoxide anion). A recombinant protein of lipopolysaccharide and β-1,3-glucan binding protein (LGBP) of the white shrimp was produced, named rLvLGBP, and examined for its binding with SDP. An ELISA binding assay showed that rLvLGBP binds to SDP with a dissociation constant of 0.0507 μM. In another experiment, shrimp fed diets containing SDP at 0 (control), 30, and 60 g kg(-1) after four weeks were examined for LGBP transcript level and lysozyme activity, as well as phagocytic activity, clearance efficiency, and resistance to Vibrio alginolyticus. These parameters were significantly higher in shrimp receiving diets containing SDP at 60 g kg(-1) or 30 g kg(-1) than in controls. In conclusion, shrimp haemocytes receiving SDP provoked the activation of innate immunity as evidenced by the recognition and binding of LGBP, degranulation of haemocytes, reduction in the percentage of large cells, increases in PO activity, serine proteinase activity, superoxide anion levels, and up-regulated LGBP transcript levels. Shrimp receiving diets containing SDP had increased lysozyme activity and resistance against V. alginolyticus infection. This study showed the mechanism underlying the immunostimulatory action of Spirulina and its immune response in shrimp. PMID:27368541

  16. Increased temperature in the thermophilic stage in temperature phased anaerobic digestion (TPAD) improves degradability of waste activated sludge.

    PubMed

    Ge, Huoqing; Jensen, Paul D; Batstone, Damien J

    2011-03-15

    Two-stage temperature phased anaerobic digestion (TPAD) is an increasingly popular method to improve stabilisation of sewage waste activated sludge, which normally has inherently poor and slow degradation. However, there has been limited systematic analysis of the impact of the initial thermophilic stage (temperature, pH and retention time) on performance in the main mesophilic stage. In this study, we demonstrate a novel two-stage batch test method for TPAD processes, and use it to optimize operating conditions of the thermophilic stage in terms of degradation extent and methane production. The method determines overall degradability and apparent hydrolysis coefficient in both stages. The overall process was more effective with short pre-treatment retention times (1-2 days) and neutral pH compared to longer retention time (4 days) and low pH (4-5). Degradabilities and apparent hydrolysis coefficients were 0.3-0.5 (fraction degradable) and 0.1-0.4d(-1), respectively, with a margin of error in each measurement of approximately 20% relative (95% confidence). Pre-treatment temperature had a strong impact on the whole process, increasing overall degradability from 0.3 to 0.5 as temperature increased from 50 to 65 °C, with apparent hydrolysis coefficient increasing from 0.1 to 0.4d(-1). PMID:21277081

  17. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

  18. NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli

    PubMed Central

    Boulanger, Anne E.; Poirel, Laurent

    2012-01-01

    A clinical Escherichia coli isolate resistant to all β-lactams, including carbapenems, expressed a novel metallo-β-lactamase (MBL), NDM-4, differing from NDM-1 by a single amino acid substitution (Met154Leu). NDM-4 possessed increased hydrolytic activity toward carbapenems and several cephalosporins compared to that of NDM-1. This amino acid substitution was not located in the known active sites of NDM-1, indicating that remote amino acid substitutions might also play a role in the extended activity of this MBL. PMID:22252797

  19. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity.

    PubMed Central

    Smart, D R; Ritchie, K; Stark, J M; Bugbee, B

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity. PMID:11536820

  20. Pharmacological profile of the ATP-mediated increase in L-type calcium current amplitude and activation of a non-specific cationic current in rat ventricular cells.

    PubMed Central

    Scamps, F; Vassort, G

    1994-01-01

    1. The pharmacological profile of the ATP-induced increase in ICa amplitude and of ATP activation of a non-specific cationic current, IATP, was investigated in rat ventricular cells. 2. The EC50 values for ICa increase and IATP activation were 0.36 microM and 0.76 microM respectively. Suramin (10 microM) and cibacron blue (1 microM) competitively antagonized both effects of ATP. 3. The rank order of efficacy and potency of ATP analogues in increasing ICa amplitude was 2-methylthio-ATP approximately ATP approximately ATP gamma S. The derivatives alpha,beta-methylene-ATP, beta,gamma-methylene-ATP and beta,gamma-imido-ATP up to 500 microM had no significant effects. 4. The rank order of efficacy of ATP analogues in activating a non-specific cationic current, IATP, was 2-methylthio-ATP > ATP >> ATP gamma S. The rank order of potency was 2-methylthio-ATP approximately ATP. The EC50 of ATP gamma S could not be determined owing to its very low efficacy. 5. The ATP analogues alpha,beta-methylene-ATP, beta,gamma-methylene-ATP and beta,gamma-imido-ATP at 500 microM did not activate IATP but acted as antagonists of activation of IATP by ATP. 6. The results suggest that the increase in ICa amplitude induced by external ATP is due to activation of P2Y-purinoceptors. 7. The mechanism of IATP activation remains to be determined before the receptor subtype involved can be deduced. PMID:7858894

  1. TRAIL-induced caspase/p38 activation is responsible for the increased catalytic and invasive activities of Akt

    PubMed Central

    SUN, BO K.; KIM, JOO-HANG; NGUYEN, HOAN N.; KIM, SO Y.; OH, SEEUN; LEE, YONG J.; SONG, JAE J.

    2010-01-01

    We previously observed that TRAIL induces acquired TRAIL resistance coinciding with increased Akt phosphorylation brought about by the Src-PI3K-Akt signaling pathways and mediated by c-Cbl. c-Cbl, a ubiquitously expressed cytoplasmic adaptor protein, is simultaneously involved in the rapid degradation of TRAIL receptors and Akt phosphorylation during TRAIL treatment. Here, we show that Akt phosphorylation is not exclusively responsible for acquired TRAIL resistance. Akt catalytic activation is known to increase during metabolic oxidative stress, but we show that TRAIL also dramatically induces the catalytic activation of Akt in TRAIL-sensitive cells, but not in TRAIL-resistant cells. This suggests that Akt catalytic activation during TRAIL-induced apoptosis is likely to play a compensatory role in the maintenance of cell homeostasis. In addition, activated p38 and phosphorylated HSP27 were found to act as downstream effector molecules of p38 during TRAIL treatment and were shown to be responsible for increased Akt catalytic and invasive activities. PMID:21109947

  2. Dihydrolipoic acid activates oligomycin-sensitive thiol groups and increases ATP synthesis in mitochondria.

    PubMed

    Zimmer, G; Mainka, L; Krüger, E

    1991-08-01

    Investigations with dihydrolipoic acid in rat heart mitochondria and mitoplasts reveal an activation of ATP-synthase up to 45%, whereas ATPase activities decrease by 36%. In parallel with an increase in ATP synthesis oligomycin-sensitive mitochondrial -SH groups are activated at 2-4 nmol dihydrolipoic acid/mg protein. ATPase activation by the uncouplers carbonylcyanide-p-trifluoromethoxyphenylhydrazone and oleate is diminished by dihydrolipoic acid, and ATP synthesis depressed by oleate is partially restored. No such efficiency of dihydrolipoic acid is seen with palmitate-induced ATPase activation or decrease of ATP synthesis. This indicates different interference of oleate and palmitate with mitochondria. In addition to its known coenzymatic properties dihydrolipoic acid may act as a substitute for coenzyme A, thereby diminishing the uncoupling efficiency of oleate. Furthermore, dihydrolipoic acid is a very potent antioxidant, shifting the -SH-S-S- equilibrium in mitochondria to the reduced state and improving the energetic state of cells. PMID:1832845

  3. Increased premotor cortex activation in high functioning autism during action observation.

    PubMed

    Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

    2015-04-01

    The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. PMID:25726458

  4. The Increasing Impact of Activity-Based Protein Profiling in Plant Science.

    PubMed

    Morimoto, Kyoko; van der Hoorn, Renier A L

    2016-03-01

    The active proteome dictates plant physiology. Yet, active proteins are difficult to predict based on transcript or protein levels, because protein activities are regulated post-translationally in their microenvironments. Over the past 10 years, activity-based protein profiling (ABPP) is increasingly used in plant science. ABPP monitors the activities of hundreds of plant proteins using tagged chemical probes that react with the active site of proteins in a mechanism-dependent manner. Since labeling is covalent and irreversible, labeled proteins can be detected and identified on protein gels and by mass spectrometry using tagged fluorophores and/or biotin. Here, we discuss general concepts, approaches and practical considerations of ABPP, before we summarize the discoveries made using 40 validated probes representing 14 chemotypes that can monitor the active state of >4,500 plant proteins. These discoveries and new opportunities indicate that this emerging functional proteomic technology is a powerful discovery tool that will have an increasing impact on plant science. PMID:26872839

  5. Aging of whiskey increases 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity.

    PubMed

    Aoshima, Hitoshi; Tsunoue, Hideaki; Koda, Hirofumi; Kiso, Yoshinobu

    2004-08-11

    1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of Japanese whiskey after various aging periods in oak barrels was measured to evaluate the antioxidative effects of whiskey. The activity of the whiskey increased with the aging period with high correlation. The activity of various types of whiskey was measured and shown to be correlated to the potentiation of the GABAA receptor response measured in a previous paper. However, the fragrant compounds in the whiskey which potentiated the GABAA receptor response had low DPPH radical scavenging activity, while phenol derivatives had high radical scavenging activity. The whiskey was extracted by pentane. The aqueous part showed the scavenging activity, whereas the pentane part did not. Thus, both the DPPH radical scavenging activity and the potentiation of the GABAA receptor response increased during whiskey aging in oak barrels, but were due to different components. The whiskey protected the H2O2-induced death of E. coli more than ethanol at the same concentration as that of the whiskey. The changes that occurred in the whiskey during aging may be the reason aged whiskies are so highly valued. PMID:15291502

  6. Increasing cleavage specificity and activity of restriction endonuclease KpnI

    PubMed Central

    Vasu, Kommireddy; Nagamalleswari, Easa; Zahran, Mai; Imhof, Petra; Xu, Shuang-yong; Zhu, Zhenyu; Chan, Siu-Hong; Nagaraja, Valakunja

    2013-01-01

    Restriction enzyme KpnI is a HNH superfamily endonuclease requiring divalent metal ions for DNA cleavage but not for binding. The active site of KpnI can accommodate metal ions of different atomic radii for DNA cleavage. Although Mg2+ ion higher than 500 μM mediates promiscuous activity, Ca2+ suppresses the promiscuity and induces high cleavage fidelity. Here, we report that a conservative mutation of the metal-coordinating residue D148 to Glu results in the elimination of the Ca2+-mediated cleavage but imparting high cleavage fidelity with Mg2+. High cleavage fidelity of the mutant D148E is achieved through better discrimination of the target site at the binding and cleavage steps. Biochemical experiments and molecular dynamics simulations suggest that the mutation inhibits Ca2+-mediated cleavage activity by altering the geometry of the Ca2+-bound HNH active site. Although the D148E mutant reduces the specific activity of the enzyme, we identified a suppressor mutation that increases the turnover rate to restore the specific activity of the high fidelity mutant to the wild-type level. Our results show that active site plasticity in coordinating different metal ions is related to KpnI promiscuous activity, and tinkering the metal ion coordination is a plausible way to reduce promiscuous activity of metalloenzymes. PMID:23963701

  7. Glucagon increases energy expenditure independently of brown adipose tissue activation in humans

    PubMed Central

    Salem, V; Izzi-Engbeaya, C; Coello, C; Thomas, D B; Chambers, E S; Comninos, A N; Buckley, A; Win, Z; Al-Nahhas, A; Rabiner, E A; Gunn, R N; Budge, H; Symonds, M E; Bloom, S R; Tan, T M; Dhillo, W S

    2016-01-01

    Aims To investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans. Methods Indirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on 18F-FDG PET/CT (n = 8) underwent a randomly allocated second 18F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4). Results We observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on 18F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not. Conclusions Glucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE. PMID:26434748

  8. Increase in the activities of glycolytic enzymes in rat lungs produced by nitrogen dioxide

    SciTech Connect

    Mochitate, K.; Miura, T.; Kubota, K.

    1985-01-01

    Male Jcl: Wistar rats were exposed to 2, 4, and 10 ppm NO/sub 2/ for 14, 10, and 7 d, respectively, to examine the effect of NO/sub 2/ on the lung glycolytic pathway, a major energy-generating system in the lung. A highly significant increase in the activities of hexokinase, phosphofructokinase, 3-phosphoglycerate kinase, pyruvate kinase (PK), and lactate dehydrogenase was observed after 5 d exposure to 10 ppm NO/sub 2/, and a significantly higher value was maintained until d 7. Similarly, the activities of all enzymes examined increased significantly by exposure to 4 ppm NO/sub 2/, reaching the maximum between 4 and 7 d of exposure, and then approached to near the control levels. The most remarkable increase was found in the PK activity, which reached 1.82- and 1.53-fold that of the control at d 5 (10 ppm) and d 7 (4 ppm) of exposure, respectively. Upon exposure to 2 ppm NO/sub 2/, the PK activity of exposed animals was also increased to 1.23-fold that of the control at d 7, and higher activity was maintained until d 14. The glucose-6-phosphate dehydrogenase activity of exposed animals increased significantly at d 3, 4, and 14 of exposures to 10, 4, and 2 ppm NO/sub 2/, respectively, and a significantly higher value was maintained in the following period of exposure. These results show that short-term exposure of rats to 2-10 ppm NO/sub 2/ induces the pulmonary systems concerning glycolysis and NADPH-generation. The generation of energy and NADPH in the lung may be enhanced by NO/sub 2/ inhalation.

  9. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

    PubMed Central

    Ma, Fei; Zhang, Liping; Westlund, Karin N

    2009-01-01

    Background Transient receptor potential vanilloid subtype 1 (TRPV1) is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α), a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1) activation. Reactive oxygen species (ROS) production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG) neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN), were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons. PMID:19531269

  10. Fatty acids and glucose increase neutral endopeptidase activity in human microvascular endothelial cells.

    PubMed

    Muangman, Pornprom; Spenny, Michelle L; Tamura, Richard N; Gibran, Nicole S

    2003-06-01

    Neutral endopeptidase (NEP), a membrane-bound metallopeptidase enzyme that degrades neuropeptides, bradykinin, atrial natriuretic factor, enkephalins, and endothelin may regulate response to injury. We have previously demonstrated increased NEP localization and enzyme activity in diabetic wounds and skin compared with normal controls. We hypothesized that hyperlipidemia and hyperglycemia associated with type 2 diabetes mellitus may induce excessive NEP activity and thereby diminish normal response to injury. Human microvascular endothelial cells were treated with five different fatty acids (40 microM) with varying degrees of saturation, including oleic acid, linoleic acid, palmitic acid, stearic acid, and linolenic acid and/or glucose (40 mM) for 48 h. The effect of the antioxidative agents vitamin E and C on NEP enzyme activation was determined by treating the cultured cells with alpha-tocopherol succinate and/or L-ascorbic acid. Cell membrane preparations were assayed for NEP activity by incubation with glutaryl-Ala-Ala-Phe-4-methoxy-beta naphthylamide to generate a fluorescent degradation product methoxy 2 naphthylamine. High glucose or fatty acid concentration upregulated NEP activity. The highest NEP activity was observed with combined elevated glucose, linoleic acid, and oleic acid (P < 0.05). Antioxidant vitamin E and C treatment significantly reduced NEP enzyme activity after fatty acid exposure (P < 0.05). Thus, hyperglycemia and hyperlipidemia associated with type 2 diabetes mellitus may increase endothelial cell NEP activity and thereby decrease early pro-inflammatory responses. The modulator effect of vitamin E and C on NEP membrane enzyme activity after exposure to fatty acid stimulation suggests that lipid oxidation may activate NEP. PMID:12785004

  11. Men on the Move: A Pilot Program to Increase Physical Activity Among African American Men

    PubMed Central

    Griffith, Derek M.; Allen, Julie Ober; Johnson-Lawrence, Vicki; Langford, Aisha

    2015-01-01

    Despite the important contribution increasing physical activity levels may play in reducing chronic disease morbidity and mortality, there is a paucity of interventions and research indicating how to improve physical activity levels in African American men. Men on the Move was a pilot study to increase African American men’s levels of physical activity by improving access to age and ability-appropriate, male-focused physical activity opportunities and facilitating access to social support from male peers. Forty-one African American men ages 35 to 70 enrolled (mean age = 53.8). Groups of 5 to 10 men met once a week with a certified personal trainer for 10 weeks. Each meeting addressed barriers to physical activity, provided men with community resources, and incorporated activities that promoted flexibility, strength, balance, and conditioning. Improvements (p < .05) were detected for the following outcome measures: perceived self-efficacy to sustain physical activity, endurance, overall health status, and stress level. Physiological and fitness outcome measures improved, although not to significant levels. Whereas 40% of the men met the recommendation of 150 minutes of moderate or vigorous physical activity weekly at baseline, 68% of the men met this recommendation by the end of the project. These positive results attest to the feasibility of successfully engaging middle-aged and older African American men in a physical activity intervention, and our findings demonstrate the initial efficacy of this intervention approach. More research is needed that includes a more intensive intervention and one that helps motivate men to be physically active outside of the structured, small-group sessions. PMID:23918885

  12. Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor

    PubMed Central

    Tucker, Erik I.; Matafonov, Anton; Cheng, Qiufang; Zientek, Keith D.; Gailani, Dave; Gruber, András; McCarty, Owen J. T.

    2015-01-01

    Activation of coagulation factor XI (FXI) may play a role in hemostasis. The primary substrate of activated FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombin generation. However, recent studies suggest the hemostatic role of FXI may not be restricted to the activation of FIX. We explored whether FXI could interact with and inhibit the activity of tissue factor pathway inhibitor (TFPI). TFPI is an essential reversible inhibitor of activated factor X (FXa) and also inhibits the FVIIa-TF complex. We found that FXIa neutralized both endothelium- and platelet-derived TFPI by cleaving the protein between the Kunitz (K) 1 and K2 domains (Lys86/Thr87) and at the active sites of the K2 (Arg107/Gly108) and K3 (Arg199/Ala200) domains. Addition of FXIa to plasma was able to reverse the ability of TFPI to prolong TF-initiated clotting times in FXI- or FIX-deficient plasma, as well as FXa-initiated clotting times in FX-deficient plasma. Treatment of cultured endothelial cells with FXIa increased the generation of FXa and promoted TF-dependent fibrin formation in recalcified plasma. Together, these results suggest that the hemostatic role of FXIa may be attributed not only to activation of FIX but also to promoting the extrinsic pathway of thrombin generation through inactivation of TFPI. PMID:25587039

  13. Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor.

    PubMed

    Puy, Cristina; Tucker, Erik I; Matafonov, Anton; Cheng, Qiufang; Zientek, Keith D; Gailani, Dave; Gruber, András; McCarty, Owen J T

    2015-02-26

    Activation of coagulation factor XI (FXI) may play a role in hemostasis. The primary substrate of activated FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombin generation. However, recent studies suggest the hemostatic role of FXI may not be restricted to the activation of FIX. We explored whether FXI could interact with and inhibit the activity of tissue factor pathway inhibitor (TFPI). TFPI is an essential reversible inhibitor of activated factor X (FXa) and also inhibits the FVIIa-TF complex. We found that FXIa neutralized both endothelium- and platelet-derived TFPI by cleaving the protein between the Kunitz (K) 1 and K2 domains (Lys86/Thr87) and at the active sites of the K2 (Arg107/Gly108) and K3 (Arg199/Ala200) domains. Addition of FXIa to plasma was able to reverse the ability of TFPI to prolong TF-initiated clotting times in FXI- or FIX-deficient plasma, as well as FXa-initiated clotting times in FX-deficient plasma. Treatment of cultured endothelial cells with FXIa increased the generation of FXa and promoted TF-dependent fibrin formation in recalcified plasma. Together, these results suggest that the hemostatic role of FXIa may be attributed not only to activation of FIX but also to promoting the extrinsic pathway of thrombin generation through inactivation of TFPI. PMID:25587039

  14. Alkalosis and Dialytic Clearance of Phosphate Increases Phosphatase Activity: A Hidden Consequence of Hemodialysis

    PubMed Central

    Villa-Bellosta, Ricardo; González-Parra, Emilio; Egido, Jesús

    2016-01-01

    Background Extracellular pyrophosphate is a potent endogenous inhibitor of vascular calcification, which is degraded by alkaline phosphatase (ALP) and generated by hydrolysis of ATP via ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1). ALP activity (as routinely measured in clinical practice) represents the maximal activity (in ideal conditions), but not the real activity (in normal or physiological conditions). For the first time, the present study investigated extracellular pyrophosphate metabolism during hemodialysis sessions (including its synthesis via eNPP1 and its degradation via ALP) in physiological conditions. Methods and Findings 45 patients in hemodialysis were studied. Physiological ALP activity represents only 4–6% of clinical activity. ALP activity increased post-hemodialysis by 2% under ideal conditions (87.4 ± 3.3 IU/L vs. 89.3 ± 3.6 IU/L) and 48% under physiological conditions (3.5 ± 0.2 IU/L vs. 5.2 ± 0.2 IU/L). Pyrophosphate synthesis by ATP hydrolysis remained unaltered post-hemodialysis. Post-hemodialysis plasma pH (7.45 ± 0.02) significantly increased compared with the pre-dialysis pH (7.26 ± 0.02). The slight variation in pH (~0.2 units) induced a significant increase in ALP activity (9%). Addition of phosphate in post-hemodialysis plasma significantly decreased ALP activity, although this effect was not observed with the addition of urea. Reduction in phosphate levels and increment in pH were significantly associated with an increase in physiological ALP activity post-hemodialysis. A decrease in plasma pyrophosphate levels (3.3 ± 0.3 μmol/L vs. 1.9 ± 0.1 μmol/L) and pyrophosphate/ATP ratio (1.9 ± 0.2 vs. 1.4 ± 0.1) post-hemodialysis was also observed. Conclusion Extraction of uremic toxins, primarily phosphate and hydrogen ions, dramatically increases the ALP activity under physiological conditions. This hitherto unknown consequence of hemodialysis suggests a reinterpretation of the clinical value of this parameter

  15. Aquaporin 5 increases keratinocyte-derived chemokine expression and NF-κB activity through ERK activation.

    PubMed

    Sakamoto, Yuima; Hisatsune, Akinori; Katsuki, Hiroshi; Horie, Ichiro; Isohama, Yoichiro

    2014-06-13

    Aquaporin-5 (AQP5) is a water-selective channel protein that is expressed in submucosal glands and alveolar epithelial cells in the lungs. Recent studies have revealed that AQPs regulate not only water metabolism, but also some cellular functions such as cell growth and migration. Here, we report the role of AQP5 in inflammatory responses. In MLE-12 cells, knockdown of AQP5 using siRNA (10-50 nM) attenuated TNF-α-induced expression of keratinocyte chemoattractant (KC) mRNA and protein. Conversely, in NIH-3T3 cells, overexpression of AQP5 increased KC expression, NF-κB activation, and ERK phosphorylation. The AQP5-induced increase of KC expression was diminished by treatment with ERK inhibitors. Taken together, we propose a new function of AQP5 as an inflammatory signal potentiator, which may be mediated by increased activation of ERK and NF-κB. PMID:24747567

  16. covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus

    PubMed Central

    Ashwinkumar Subramenium, Ganapathy; Viszwapriya, Dharmaprakash; Iyer, Prasanth Mani; Balamurugan, Krishnaswamy; Karutha Pandian, Shunmugiah

    2015-01-01

    Background Group A streptococcus (GAS, Streptococcus pyogenes), a multi-virulent, exclusive human pathogen responsible for various invasive and non-invasive diseases possesses biofilm forming phenomenon as one of its pathogenic armaments. Recently, antibiofilm agents have gained prime importance, since inhibiting the biofilm formation is expected to reduce development of antibiotic resistance and increase their susceptibility to the host immune cells. Principal Findings The current study demonstrates the antibiofilm activity of 3Furancarboxaldehyde (3FCA), a floral honey derived compound, against GAS biofilm, which was divulged using crystal violet assay, light microscopy, and confocal laser scanning microscopy. The report is extended to study its effect on various aspects of GAS (morphology, virulence, aggregation) at its minimal biofilm inhibitory concentration (132μg/ml). 3FCA was found to alter the growth pattern of GAS in solid and liquid medium and increased the rate of auto-aggregation. Electron microscopy unveiled the increase in extra polymeric substances around cell. Gene expression studies showed down-regulation of covR gene, which is speculated to be the prime target for the antibiofilm activity. Increased hyaluronic acid production and down regulation of srtB gene is attributed to the enhanced rate of auto-aggregation. The virulence genes (srv, mga, luxS and hasA) were also found to be over expressed, which was manifested with the increased susceptibility of the model organism Caenorhabditis elegans to 3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C. elegans. Significance Though 3FCA possess antibiofilm activity against GAS, it was also found to increase the virulence of GAS. This study demonstrates that, covR mediated antibiofilm activity may increase the virulence of GAS. This also emphasizes the importance to analyse the acclimatization response and virulence of the pathogen in the presence of antibiofilm compounds

  17. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen.

    PubMed

    Shi, Zhigang; Brooks, Virginia L

    2015-04-01

    Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR in ovariectomized rats, but its effects were normalized with 4 days of oestrogen treatment. Bilateral nanoinjection of SHU9119 into the paraventricular nucleus of the hypothalamus (PVN), to block α-melanocyte-stimulating hormone (α-MSH) type 3 and 4 receptors, decreased LSNA in leptin-treated pro-oestrus but not dioestrus rats. Unlike leptin, i.c.v. insulin infusion increased basal and baroreflex control of LSNA and HR similarly in pro-oestrus and dioestrus rats; these responses did not differ from those in male rats. We conclude that, in female rats, leptin's stimulatory effects on SNA are differentially enhanced by oestrogen, at least in part via an increase in α-MSH activity in the PVN. These data further suggest that the actions of leptin and insulin to increase the activity of various sympathetic nerves occur via different neuronal pathways or cellular mechanisms. These results may explain the poor correlation in females of SNA with adiposity, or of MAP with leptin. PMID:25398524

  18. Paradoxical control properties of enzymes within pathways: can activation cause an enzyme to have increased control?

    PubMed Central

    Kholodenko, B N; Brown, G C

    1996-01-01

    It is widely assumed that within a metabolic pathway inhibition of an enzyme causes the control exerted by that enzyme over the flux through its own reaction to increase, whereas activation causes its control to decrease. This assumption forms the basis of a number of experimental methods. For a pathway conceptually divided into two enzyme groups connected via a single metabolite we have derived a general condition under which this assumption is false, and thus the pathway shows paradoxical control behaviour, i.e. increased control with activation and decreased control with inhibition of an enzyme or group of enzymes. Paradoxical control behaviour occurs widely when enzyme activity is altered by changing Km (if an enzyme is already close to saturation by its substrate), but may also occur with changes in Vmax. when the elasticity to the linking metabolite increases with its concentration (as in some cases of sigmoidal and exponential kinetics or for reactions catalysed by isoenzymes). These findings suggest that enzymes with sigmoidal kinetics may have low control in the absence of activation, but may gain control with activation, and thus have beneficial regulatory properties. PMID:8615766

  19. Greater electroencephalographic coherence between left and right temporal lobe structures during increased geomagnetic activity.

    PubMed

    Saroka, Kevin S; Caswell, Joseph M; Lapointe, Andrew; Persinger, Michael A

    2014-02-01

    Interhemispheric coherence for 19 channel EEG activity collected over a three year period from 184 men and women who relaxed in a quiet, darkened chamber showed significant increased coherence between caudal temporal regions for the 11 Hz frequency band during increased (>∼8 nT) global geomagnetic activity at the time of measurement. Detailed analyses from source-localization indicated that a likely origin was the parahippocampal regions whose net differences at 10, 11 and 12 Hz intervals were significantly correlated with geomagnetic activity. Analyses of residuals to obtain a "purer" measure of parahippocampal contributions indicated that interhemispheric temporal lobe coherence across unit increments between 1 and 40 Hz revealed the most statistically significant peaks at 7.5 Hz and 19.5 Hz. These weak but reliable correlations between global geomagnetic activity and the degree of inter-temporal lobe coherence for normal people relaxing in a dark, quiet area are consistent with the results of multiple studies indicating that intrusive experiences such as "presences" or "hallucinations" are more frequent when global geomagnetic activity increases above ∼15-20 nT. PMID:24287380

  20. Cocaine Increases Dopaminergic Neuron and Motor Activity via Midbrain α1 Adrenergic Signaling

    PubMed Central

    Goertz, Richard Brandon; Wanat, Matthew J; Gomez, Jorge A; Brown, Zeliene J; Phillips, Paul EM; Paladini, Carlos A

    2015-01-01

    Cocaine reinforcement is mediated by increased extracellular dopamine levels in the forebrain. This neurochemical effect was thought to require inhibition of dopamine reuptake, but cocaine is still reinforcing even in the absence of the dopamine transporter. Here, we demonstrate that the rapid elevation in dopamine levels and motor activity elicited by cocaine involves α1 receptor activation within the ventral midbrain. Activation of α1 receptors increases dopaminergic neuron burst firing by decreasing the calcium-activated potassium channel current (SK), as well as elevates dopaminergic neuron pacemaker firing through modulation of both SK and the hyperpolarization-activated cation currents (Ih). Furthermore, we found that cocaine increases both the pacemaker and burst-firing frequency of rat ventral-midbrain dopaminergic neurons through an α1 adrenergic receptor-dependent mechanism within the ventral tegmental area and substantia nigra pars compacta. These results demonstrate the mechanism underlying the critical role of α1 adrenergic receptors in the regulation of dopamine neurotransmission and behavior by cocaine. PMID:25374094

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

    SciTech Connect

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

    2011-10-14

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

  2. Reminiscence Activity and Increased Communication Interaction among Cognitively Disabled Elderly Women.

    ERIC Educational Resources Information Center

    Krupar, Karen R.; Smith, N. Richmond

    Designed as the first phase of a larger project to explore the relationships between the possible impact of reminiscence on memory deterioration in elderly women confined to nursing home environments, a study demonstrated that reminiscence activity is positively correlated with increases in communication interactions. Women were chosen as the…

  3. DIETARY PROTEIN AND LACTOSE INCREASE TRANSLATION INITIATION FACTOR ACTIVATION AND TISSUE PROTEIN SYNTHESIS IN NEONATAL PIGS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protein synthesis and eukaryotic initiation factor (eIF) activation are increased in muscle and liver of pigs parenterally infused with amino acids and insulin. To examine the effects of enteral protein and carbohydrate on protein synthesis, pigs (n = 42, 1.7 kg body wt) were fed isocaloric milk die...

  4. An increase of Optical Activity in the Quasar 3C454.3

    NASA Astrophysics Data System (ADS)

    Jorstad, Svetlana

    2016-06-01

    The quasar 3C454.3 shows an increase of the optical activity during the last three nights. According to our observations at the Perkins telescope of the Lowell Observatory (Flagstaff, AZ) the brightness of the source on June 10 (JD 2457549.8770) in R band was 15.817+-0.018 with a of polarization of 2.27+-0.39%.

  5. Cyclic strain increases protease-activated receptor-1 expression in vascular smooth muscle cells

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    Cyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression. This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces.

  6. Text Messaging as a Tool to Increase Physical Activity in College Students

    ERIC Educational Resources Information Center

    Muñoz, Laura R.; La France, Kevin; Dominguez, Daniel; Goei, Kathleen; Herbers, Sharon; Gunter, M. Danielle; Fike, David; Carleton, William; Etnyre, Annette; Richardson, Cynthia; Allwein, David; Rauschhuber, Maureen; Norgan, Gary; Moore, Renée; Marquise, Lisa; Jones, Mary Elaine

    2014-01-01

    The purpose of this study was to assess the effectiveness of text messaging with pedometer intervention for increasing physical activity of college students. Using a two-group prospective randomized intervention-based design, the researchers gave 201 college students pedometers and divided them into intervention and control groups. The…

  7. NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway.

    PubMed

    Thakkar, Chandni S; Kate, Abhijeet S; Desai, Dattatraya C; Ghosh, Asit Ranjan; Kulkarni-Almeida, Asha A

    2015-12-15

    NFAT-133 is an aromatic compound with cinammyl alcohol moiety, isolated from streptomycetes strain PM0324667. We have earlier reported that NFAT-133 increases insulin stimulated glucose uptake in L6 myotubes using a PPARγ independent mechanism and reduces plasma or blood glucose levels in diabetic mice. Here we investigated the effects of NFAT-133 on cellular signaling pathways leading to glucose uptake in L6 myotubes. Our studies demonstrate that NFAT-133 increases glucose uptake in a dose- and time-dependent manner independent of the effects of insulin. Treatment with Akti-1/2, wortmannin and increasing concentrations of insulin had no effect on NFAT-133 mediated glucose uptake. NFAT-133 induced glucose uptake is completely mitigated by Compound C, an AMPK inhibitor. Further, the kinases upstream of AMPK activation namely; LKB-1 and CAMKKβ are not involved in NFAT-133 mediated AMPK activation nor does the compound NFAT-133 have any effect on AMPK enzyme activity. Further analysis confirmed that NFAT-133 indirectly activates AMPK by reducing the mitochondrial membrane potential and increasing the ratio of AMP:ATP. PMID:26546724

  8. Oxidized LDL levels are increased in HIV infection and may drive monocyte activation

    PubMed Central

    Zidar, David A.; Juchnowski, Steven; Ferrari, Brian; Clagett, Brian; Pilch-Cooper, Heather A.; Rose, Shawn; Rodriguez, Benigno; McComsey, Grace A.; Sieg, Scott F.; Mehta, Nehal N.; Lederman, Michael M.; Funderburg, Nicholas T.

    2015-01-01

    Background Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized LDL particles and monocyte activation. Methods We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, soluble CD163 were measured by ELISA. In vitro experiments were performed using flow cytometry. Results Plasma levels of oxLDL were significantly increased in HIV-infection compared to controls (60.1 units vs 32.1 units, p<0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, were also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, TF expression on inflammatory monocytes, and CD36. In vitro, stimulation with oxLDL, but not to LDL, resulted in expansion of inflammatory monocytes and increased monocyte expression of TF, recapitulating the monocyte profile we find in HIV disease. Conclusions OxLDL may contribute to monocyte activation and further study in the context of HIV disease is warranted. PMID:25647528

  9. 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…

  10. Planar fuel cell utilizing nail current collectors for increased active surface area

    DOEpatents

    George, Thomas J.; Meacham, G. B. Kirby

    2002-03-26

    A plurality of nail current collector members are useful in the gas flow passages of an electrochemical device to optimize the active surfaces of the device and to provide structural support. In addition, the thicknesses of cathode and anode layers within the electrochemical device are varied according to current flow through the device to reduce resistance and increase operating efficiency.

  11. Integrated Health and Physical Education Program to Reduce Media Use and Increase Physical Activity in Youth

    ERIC Educational Resources Information Center

    Clocksin, Brian D.; Wattson, Doris L.; Williams, Daniel P.; Randsell, Lynda

    2009-01-01

    The purpose of this project was to compare an integrated health and physical education curriculum, focused on reducing media use and on increasing physical activity in middle school adolescents, to traditional and nonintegrated health and physical education curricula. Two middle schools' health and physical education classes were assigned to an…

  12. Increased skeletal VEGF enhances β-catenin activity and results in excessively ossified bones

    PubMed Central

    Maes, Christa; Goossens, Steven; Bartunkova, Sonia; Drogat, Benjamin; Coenegrachts, Lieve; Stockmans, Ingrid; Moermans, Karen; Nyabi, Omar; Haigh, Katharina; Naessens, Michael; Haenebalcke, Lieven; Tuckermann, Jan P; Tjwa, Marc; Carmeliet, Peter; Mandic, Vice; David, Jean-Pierre; Behrens, Axel; Nagy, Andras; Carmeliet, Geert; Haigh, Jody J

    2010-01-01

    Vascular endothelial growth factor (VEGF) and β-catenin both act broadly in embryogenesis and adulthood, including in the skeletal and vascular systems. Increased or deregulated activity of these molecules has been linked to cancer and bone-related pathologies. By using novel mouse models to locally increase VEGF levels in the skeleton, we found that embryonic VEGF over-expression in osteo-chondroprogenitors and their progeny largely pheno-copied constitutive β-catenin activation. Adult induction of VEGF in these cell populations dramatically increased bone mass, associated with aberrant vascularization, bone marrow fibrosis and haematological anomalies. Genetic and pharmacological interventions showed that VEGF increased bone mass through a VEGF receptor 2- and phosphatidyl inositol 3-kinase-mediated pathway inducing β-catenin transcriptional activity in endothelial and osteoblastic cells, likely through modulation of glycogen synthase kinase 3-β phosphorylation. These insights into the actions of VEGF in the bone and marrow environment underscore its power as pleiotropic bone anabolic agent but also warn for caution in its therapeutic use. Moreover, the finding that VEGF can modulate β-catenin activity may have widespread physiological and clinical ramifications. PMID:20010698

  13. The effect of increase in baggage weight on elderly women's lower extremity muscle activation during gait.

    PubMed

    Kim, Seong-Gil; Nam, Chan-Woo; Yong, Min-Sik

    2014-01-01

    The aim of the present study was to examine the effect of increased baggage weight on the muscle activation of elderly women's lower extremities during gait. A total of 24 elderly women who were residing in communities in Daegu, South Korea aged 79.6±6.2, 149.7±7.0cm in height, and 53.5±7.2kg in weight participated in this study. The muscle activation of each muscle was measured three times at 2kg, 3kg, and 4kg of baggage weight while the subjects were conducting treadmill walking wearing backpacks. Electrodes were placed on four muscles: the quadriceps muscle (rectus femoris), the hamstring muscle (semitendinosus), the tibialis anterior muscle, and the soleus muscle. The results show that the rates of increase in muscle activation in the tibialis anterior and soleus muscles according to baggage weight increase were higher than those in the quadriceps and hamstring muscles (<0.05). These results indicate that the heavier weight loads increase the activation of muscles that control the ankle joints causing muscle fatigue. Moreover, a decrease in balance ability through muscle fatigue can be a risk factor for falls. Thus, elderly people should be instructed not to carry heavy objects. PMID:25179442

  14. Peers Increase Adolescent Risk Taking by Enhancing Activity in the Brain's Reward Circuitry

    ERIC Educational Resources Information Center

    Chein, Jason; Albert, Dustin; O'Brien, Lia; Uckert, Kaitlyn; Steinberg, Laurence

    2011-01-01

    The presence of peers increases risk taking among adolescents but not adults. We posited that the presence of peers may promote adolescent risk taking by sensitizing brain regions associated with the anticipation of potential rewards. Using fMRI, we measured brain activity in adolescents, young adults, and adults as they made decisions in a…

  15. Increasing Student Involvement in Self-Governance Activities: A Delphi Approach.

    ERIC Educational Resources Information Center

    Miles, Jennifer M.; Miller, Michael T.

    This study used a Delphi survey to examine what undergraduate student government leaders think about increasing student involvement in self-governance activities. Twenty-students from geographically diverse institutions of higher education participated in the three rounds of the Delphi study. They generated a total of 56 different strategies and…

  16. 78 FR 75905 - Credit for Increasing Research Activities: Intra-Group Gross Receipts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-13

    ... similar provisions of the Code. See, e.g., Prop. Reg. Sec. 1.199-1, 70 FR 67220, 67236 (November 4, 2005...; ] DEPARTMENT OF TREASURY Internal Revenue Service 26 CFR Part 1 RIN 1545-BE14 Credit for Increasing Research Activities: Intra-Group Gross Receipts AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice...

  17. Increasing Children's Physical Activity: Individual, Social, and Environmental Factors Associated with Walking to and from School

    ERIC Educational Resources Information Center

    Trapp, Georgina S. A.; Giles-Corti, Billie; Christian, Hayley E.; Bulsara, Max; Timperio, Anna F.; McCormack, Gavin R.; Villaneuva, Karen P.

    2012-01-01

    Background. Efforts to increase the prevalence of children's active school transport require evidence to inform the development of comprehensive interventions. This study used a multilevel ecological framework to investigate individual, social, and environmental factors associated with walking to and from school among elementary school-aged…

  18. Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats.

    PubMed

    da Silva Mattos, Alexandro Márcio; Xavier, Carlos Henrique; Karlen-Amarante, Marlusa; da Cunha, Natália Veronez; Fontes, Marco Antonio Peliky; Martins-Pinge, Marli Cardoso

    2012-08-01

    The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity. PMID:22705582

  19. Successful face recognition is associated with increased prefrontal cortex activation in autism spectrum disorder.

    PubMed

    Herrington, John D; Riley, Meghan E; Grupe, Daniel W; Schultz, Robert T

    2015-04-01

    This study examines whether deficits in visual information processing in autism-spectrum disorder (ASD) can be offset by the recruitment of brain structures involved in selective attention. During functional MRI, 12 children with ASD and 19 control participants completed a selective attention one-back task in which images of faces and houses were superimposed. When attending to faces, the ASD group showed increased activation relative to control participants within multiple prefrontal cortex areas, including dorsolateral prefrontal cortex (DLPFC). DLPFC activation in ASD was associated with increased response times for faces. These data suggest that prefrontal cortex activation may represent a compensatory mechanism for diminished visual information processing abilities in ASD. PMID:25234479

  20. Increasing girls’ physical activity during an organised youth sport basketball program: a randomised controlled trial protocol

    PubMed Central

    2014-01-01

    Background Participation in organised youth sports (OYS) has been recommended as an opportunity to increase young peoples’ moderate-to-vigorous physical activity (MVPA) levels. Participants, however, spend a considerable proportion of time during OYS inactive. The purpose of this study, therefore, was to investigate whether coaches who attended coach education sessions (where education on increasing MVPA and decreasing inactivity during training was delivered) can increase players’ MVPA during training sessions over a 5-day basketball program compared to coaches who did not receive coach education sessions. Methods/design A convenience sample of 80 female players and 8 coaches were recruited into the UWS School Holiday Basketball Program in Greater Western Sydney, Australia. A two-arm, parallel-group randomised controlled trial was employed to investigate whether coaches who attended 2 coach education sessions (compared with a no-treatment control) can increase their players’ MVPA during training sessions over a 5-day basketball program. Objectively measured physical activity, directly observed lesson context and leader behaviour, player motivation, players’ perceived autonomy support, and coaching information (regarding training session planning, estimations on player physical activity and lesson context during training, perceived ability to modify training sessions, perceived importance of physical activity during training, intention to increase physical activity/reduce inactivity, and likelihood of increasing physical activity/reducing inactivity) were assessed at baseline (day 1) and at follow-up (day 5). Linear mixed models will be used to analyse between arm differences in changes from baseline to follow-up on all outcomes. Discussion The current trial protocol describes, to our knowledge, the first trial conducted in an OYS context to investigate the efficacy of an intervention, relative to a control, in increasing MVPA. This study’s findings will

  1. Lumbricus terrestris L. activity increases the availability of metals and their accumulation in maize and barley.

    PubMed

    Ruiz, E; Alonso-Azcárate, J; Rodríguez, L

    2011-03-01

    The effect of the earthworm Lumbricus terrestris L. on metal availability in two mining soils was assessed by means of chemical extraction methods and a pot experiment using crop plants. Results from single and sequential extractions showed that L. terrestris had a slight effect on metal fractionation in the studied soils: only metals bound to the soil organic matter were significantly increased in some cases. However, we found that L. terrestris significantly increased root, shoot and total Pb and Zn concentrations in maize and barley for the soil with the highest concentrations of total and available metals. Specifically, shoot Pb concentration was increased by a factor of 7.5 and 3.9 for maize and barley, respectively, while shoot Zn concentration was increased by a factor of 3.7 and 1.7 for maize and barley, respectively. Our results demonstrated that earthworm activity increases the bioavailability of metals in soils. PMID:21190761

  2. The TMS Map Scales with Increased Stimulation Intensity and Muscle Activation.

    PubMed

    van de Ruit, Mark; Grey, Michael J

    2016-01-01

    One way to study cortical organisation, or its reorganisation, is to use transcranial magnetic stimulation (TMS) to construct a map of corticospinal excitability. TMS maps are reported to be acquired with a wide variety of stimulation intensities and levels of muscle activation. Whilst MEPs are known to increase both with stimulation intensity and muscle activation, it remains to be established what the effect of these factors is on the map's centre of gravity (COG), area, volume and shape. Therefore, the objective of this study was to systematically examine the effect of stimulation intensity and muscle activation on these four key map outcome measures. In a first experiment, maps were acquired with a stimulation intensity of 110, 120 and 130% of resting threshold. In a second experiment, maps were acquired at rest and at 5, 10, 20 and 40% of maximum voluntary contraction. Map area and map volume increased with both stimulation intensity (P < 0.01) and muscle activation (P < 0.01). Neither the COG nor the map shape changed with either stimulation intensity or muscle activation (P > 0.09 in all cases). This result indicates the map simply scales with stimulation intensity and muscle activation. PMID:26337508

  3. Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

    PubMed Central

    Ancuta, Petronela; Kamat, Anupa; Kunstman, Kevin J.; Kim, Eun-Young; Autissier, Patrick; Wurcel, Alysse; Zaman, Tauheed; Stone, David; Mefford, Megan; Morgello, Susan; Singer, Elyse J.; Wolinsky, Steven M.; Gabuzda, Dana

    2008-01-01

    Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes. PMID:18575590

  4. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance

    SciTech Connect

    Beckman, J.S.; Minor, R.L. Jr.; White, C.W.; Repine, J.E.; Rosen, G.M.; Freeman, B.A.

    1988-05-15

    Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from <10 min to 40 h, reduced immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, the authors hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with /sup 125/I-PEG-catalase or /sup 125/I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.

  5. Increasing total and biologically active chromium in wheat grain and spinach by spraying with chromium salts

    SciTech Connect

    Vicini, F.A.; Ellis, B.G.

    1981-06-01

    Recently, chromium has been shown to be necessary for glucose metabolism in man. But most plant species greatly restrict the uptake of Cr. This study was conducted to determine if both total and biologically active Cr could be increased in wheat grain or spinach by spraying the plants with either Cr/sub 2/(SO/sub 4/)/sub 3/ or Cr-EDTA. Concentrations of Cr in wheat grain were about doubled in a greenhouse experiment by spraying with either Cr source. Biologically active Cr (estimated by extraction with ethanol or NH/sub 4/OH) was increased from about 40 to greater than 50% of total Cr when wheat was sprayed with Cr salts. Total Cr in spinach leaves was increased by as much as 10-fold by spraying, with the sulfate source being more effective than the EDTA.

  6. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    SciTech Connect

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  7. Alpha-Amylase Activity in Blood Increases after Pharmacological, But Not Psychological, Activation of the Adrenergic System

    PubMed Central

    Nater, Urs M.; La Marca, Roberto; Erni, Katja; Ehlert, Ulrike

    2015-01-01

    Background & Aim Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separate studies. Methods In study 1, healthy subjects were examined in a placebo-controlled, double-blind paradigm using yohimbine, an alpha2-adrenergic antagonist. In study 2, subjects were examined in a standardized rest-controlled psychosocial stress protocol. Alpha-amylase activity in blood was repeatedly measured in both studies. Results Results of study 1 showed that alpha-amylase in blood is subject to stronger increases after injection of yohimbine compared to placebo. In study 2, results showed that there was no significant effect of psychological stress compared to rest. Conclusions Alpha-amylase in blood increases after pharmacological activation of the adrenergic pathways suggesting that sympathetic receptors are responsible for these changes. Psychological stress, however, does not seem to have an impact on alpha-amylase in blood. Our findings provide insight into the mechanisms underlying activity changes in alpha-amylase in blood in healthy individuals. PMID:26110636

  8. Increased digitalis-like activity in human cerebrospinal fluid after expansion of the extracellular fluid volume

    SciTech Connect

    Halperin, J.A.; Martin, A.M.; Malave, S.

    1985-08-12

    The present study was designed to determine whether acute expansion of the extracellular fluid volume influenced the digitalis-like activity of human cerebrospinal fluid (CSF), previously described. Human CSF samples, drawn before and 30 minutes after the intravenous infusion of 1 liter of either saline or glucose solutions, were assayed for digitalis-like activity by inhibition of either the /sup 86/Rb/sup +/ uptake into human erythrocytes or by the activity of a purified Na/sup +/-K/sup +/ ATPase. The CSF inhibitory activity on both systems significantly increased after the infusion of sodium solutions but did not change after the infusion of glucose. These results indicate that the digitalis-like factor of human CSF might be involved in the regulation of the extracellular fluid volume and electrolyte content and thereby in some of the physiological responses to sodium loading. 31 references, 2 figures, 1 table.

  9. Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity.

    PubMed

    Rezcallah, Myrna S; Boyle, Michael D P; Sledjeski, Darren D

    2004-02-01

    The plasminogen activator streptokinase has been proposed to be a key component of a complex mechanism that promotes skin invasion by Streptococcus pyogenes. This study was designed to compare ska gene message and protein levels in wild-type M1 serotype isolate 1881 and a more invasive variant recovered from the spleen of a lethally infected mouse. M1 isolates selected for invasiveness demonstrated enhanced levels of active plasminogen activator activity in culture. This effect was due to a combination of increased expression of the ska gene and decreased expression of the speB gene. The speB gene product, SpeB, was found to efficiently degrade streptokinase in vitro. PMID:14766914

  10. Decreases in Theta and Increases in High Frequency Activity Underlie Associative Memory Encoding

    PubMed Central

    Greenberg, Jeffrey A.; Burke, John F.; Haque, Rafi; Kahana, Michael J.; Zaghloul, Kareem A.

    2015-01-01

    Episodic memory encoding refers to the cognitive process by which items and their associated contexts are stored in memory. To investigate changes directly attributed to the formation of explicit associations, we examined oscillatory power captured through intracranial electroencephalography (iEEG) as 27 neurosurgical patients receiving subdural and depth electrodes for seizure monitoring participated in a paired associates memory task. We examined low (3–8 Hz) and high (45–95 Hz) frequency activity, and found that the successful formation of new associations was accompanied by broad decreases in low frequency activity and a posterior to anterior progression of increases in high frequency activity in the left hemisphere. These data suggest that the observed patterns of activity may reflect the neural mechanisms underlying the formation of novel item-item associations. PMID:25862266

  11. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    NASA Astrophysics Data System (ADS)

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-02-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

  12. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    PubMed Central

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-01-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology. PMID:26861509

  13. Increased Activity of Rhizosphere and Hyphosphere Enzymes under Elevated CO2 in a Loblolly Pine Stand

    NASA Astrophysics Data System (ADS)

    Meier, I.; Phillips, R.

    2012-12-01

    The stimulatory effect of elevated atmospheric CO2 under global climate change on forest productivity has been predicted to decrease over time as pools of available N in soil become depleted, but empirical support for such progressive N limitation has been lacking. Increased N acquisition from soil depleted in inorganic nitrogen requires stimulation of the microbial processing of organic N, possibly through increasing C supply to soil by plant roots or mycorrhizal hyphae. Increases in (mycorr)rhizosphere C fluxes could stimulate microbes to produce extra-cellular enzymes that release N from SOM, feeding back from soil microsites to ecosystem-scale processes. We investigated the influence of elevated CO2 on root exudation and soil enzyme activity at the Duke Forest FACE site, USA, where loblolly pine (Pinus taeda L.) stands have been exposed to elevated CO2 for 14 years and N fertilization for five years. In each plot, root boxes containing acetate windows were installed in 2008. Two years after installation, we collected soils adjacent to root tips (the rhizosphere), hyphal tips (the hyphosphere) and bulk soil. We measured in situ root exudation rates from intact pine roots. Study objectives were to analyze (i) the influence of atmospheric CO2 on root exudation and extra-cellular enzyme activities, (ii) the influence of soil N availability in regulating these activities, and (iii) the relationship between the activities of enzymes involved in N cycling in soils and gross N transformations at soil microsites. Elevated atmospheric CO2 significantly increased the activity of β-1-4-N-acetylglucosaminidase (NAG) in the rhizosphere by almost 2.5 times (39 to 95 nmol h-1 g-1), and 1.6fold in the hyphosphere relative to ambient plots. NAG is an enzyme involved in the degradation of chitin from the cell walls of soil organisms, releasing absorbable forms of nitrogen. The activity of peroxidase, which degrades aromatic C compounds of SOM, increased significantly in the

  14. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    PubMed Central

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to

  15. Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability

    PubMed Central

    Escudero-Pérez, Beatriz; Volchkova, Valentina A.; Dolnik, Olga; Lawrence, Philip; Volchkov, Viktor E.

    2014-01-01

    During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNFα, IL1β, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity. PMID:25412102

  16. Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

    PubMed

    Ogawa, N; Satsu, H; Watanabe, H; Fukaya, M; Tsukamoto, Y; Miyamoto, Y; Shimizu, M

    2000-03-01

    To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing. PMID:10702577

  17. Yearning for connection? Loneliness is associated with increased ventral striatum activity to close others.

    PubMed

    Inagaki, Tristen K; Muscatell, Keely A; Moieni, Mona; Dutcher, Janine M; Jevtic, Ivana; Irwin, Michael R; Eisenberger, Naomi I

    2016-07-01

    Loneliness is a distressing state indicating that one's basic need for social connection is not being met. In an effort to satisfy the need for social connection, loneliness may increase the processing of social cues and desire to connect with others. Yet the neural substrates that contribute to the drive for increased connection in response to loneliness are not known. The ventral striatum (VS), previously shown to increase in response to craving food and other rewarding stimuli, may contribute to "social craving" when one is lonely. That is, the VS may track one's 'hunger' for reconnection much as it tracks hunger for food. To examine this, participants reported on their feelings of loneliness before undergoing an fMRI scan where they viewed cues of potential social reconnection (images of a close other). Consistent with the hypothesis that loneliness stems from an unmet need for connection, loneliness was associated with reduced feelings of connection with the close other. Furthermore, greater reported loneliness was associated with increased VS activity to viewing a close other (vs stranger). Results extend the current literature by showing that lonely individuals show increased activity in reward-related regions to their closest loved ones, possibly reflecting an increased desire for social connection. PMID:26084531

  18. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons

    PubMed Central

    Orellana, Juan A.; Moraga-Amaro, Rodrigo; Díaz-Galarce, Raúl; Rojas, Sebastián; Maturana, Carola J.; Stehberg, Jimmy; Sáez, Juan C.

    2015-01-01

    Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression. PMID:25883550

  19. Net Increase of platelet membrane tyrosine specific-protein kinase activity by phorbol myristate acetate

    SciTech Connect

    Ishihara, Noriko; Sakamoto, Hikaru; Iwama, Minako; Kobayashi, Bonro )

    1990-01-01

    Tyrosine protein kinase (TPK) activity in rabbit platelets after stimulation by phorbol myristate acetate (PMA) or thrombin was directly estimated by {sup 32}P incorporation from ({gamma}-{sup 32})ATP into synthetic peptide angiotensin II. By PMA-treatment a net increase of TPK activity was obtained, while thrombin acted on the TPK quickly but stimulation was limited within the range attained by the control after lengthy incubation. The responsive TPK to these stimulators was localized mainly in membrane but much less in cytosol. The specific activity of the particulate TPK was low in the sonicate of control ice cold platelets but increased about 6-fold when the platelets were incubated at 37{degree}C. On a brief contact of platelets with PMA at 37{degrees}C the TPK was fully activated and reached a maximum value about 130% of the control. Determination of phosphotyrosine phosphatase in the stimulated platelet sonicate revealed that its participation in the above described increase of {sup 32}P-incorporation was meagre. The quick response suggested a possible role of TPK in the signal transduction through the platelet cell membrane.

  20. PD-1 Increases PTEN Phosphatase Activity While Decreasing PTEN Protein Stability by Inhibiting Casein Kinase 2

    PubMed Central

    Patsoukis, Nikolaos; Li, Lequn; Sari, Duygu; Petkova, Victoria

    2013-01-01

    Programmed death 1 (PD-1) is a potent inhibitor of T cell responses. PD-1 abrogates activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but the mechanism remains unclear. We determined that during T cell receptor (TCR)/CD3- and CD28-mediated stimulation, PTEN is phosphorylated by casein kinase 2 (CK2) in the Ser380-Thr382-Thr383 cluster within the C-terminal regulatory domain, which stabilizes PTEN, resulting in increased protein abundance but suppressed PTEN phosphatase activity. PD-1 inhibited the stabilizing phosphorylation of the Ser380-Thr382-Thr383 cluster within the C-terminal domain of PTEN, thereby resulting in ubiquitin-dependent degradation and diminished abundance of PTEN protein but increased PTEN phosphatase activity. These effects on PTEN were secondary to PD-1-mediated inhibition of CK2 and were recapitulated by pharmacologic inhibition of CK2 during TCR/CD3- and CD28-mediated stimulation without PD-1. Furthermore, PD-1-mediated diminished abundance of PTEN was reversed by inhibition of ubiquitin-dependent proteasomal degradation. Our results identify CK2 as a new target of PD-1 and reveal an unexpected mechanism by which PD-1 decreases PTEN protein expression while increasing PTEN activity, thereby inhibiting the PI3K/Akt signaling axis. PMID:23732914

  1. Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids.

    PubMed

    Haynes, Johnson; Obiako, Boniface

    2002-01-01

    This study investigates the role of the activated polymorphonuclear cell (APMN) products on sickle red blood cell (SRBC) retention/adherence in the pulmonary circulation. Isolated rat lungs were perfused with (51)Cr-labeled normal RBCs (NRBC) or SRBCs (10% hematocrit) suspensions +/- PMNs. Specific activities of lung and perfusate were measured and retention (the number of SRBC/g lung) was calculated. SRBC retention was 3.5 times greater than NRBC retention. PMN activation was required to increase SRBC retention. Supernatants from APMN increased SRBC retention, which suggested soluble products such as oxidants, PAF, and/or leukotriene (LTB(4)) are involved. Heat inactivation of PMN NADPH oxidase had no effect on retention. Whereas neither platelet-activating factor (PAF) nor LTB(4) (secreted by APMN) increased SRBC retention, PAF+LTB(4) did. The PAF antagonist, WEB-2170, attenuated SRBC retention mediated by PAF+LTB(4) and APMNs. Similarly, zileuton (5-lipoxygenase inhibitor) attenuated APMN-mediated SRBC retention. We conclude the concomitant release of PAF and LTB(4) from APMN is involved in the initiation of microvascular occlusion by SRBCs in the perfused rat lung. PMID:11748055

  2. Prenatal Iron Deficiency in Guinea Pigs Increases Locomotor Activity but Does Not Influence Learning and Memory

    PubMed Central

    Fiset, Catherine; Rioux, France M.; Surette, Marc E.; Fiset, Sylvain

    2015-01-01

    The objective of the current study was to determine whether prenatal iron deficiency induced during gestation in guinea pigs affected locomotor activity and learning and memory processes in the progeny. Dams were fed either iron-deficient anemic or iron-sufficient diets throughout gestation and lactation. After weaning, all pups were fed an iron-sufficient diet. On postnatal day 24 and 40, the pups’ locomotor activity was observed within an open-field test, and from postnatal day 25 to 40, their learning and memory processes were assessed within a Morris Water Maze. The behavioural and cognitive tests revealed that the iron deficient pup group had increased locomotor activity, but solely on postnatal day 40, and that there were no group differences in the Morris Water Maze. In the general discussion, we propose that prenatal iron deficiency induces an increase in nervousness due to anxiety in the progeny, which, in the current study, resulted in an increase of locomotor activity. PMID:26186713

  3. Porcine malignant hyperthermia susceptibility: increased calcium-sequestering activity of skeletal muscle sarcoplasmic reticulum.

    PubMed Central

    O'Brien, P J

    1986-01-01

    This study tested the hypothesis that calcium-sequestration by isolated sarcoplasmic reticulum was abnormal in skeletal muscle of malignant hyperthermia-susceptible swine. A heavy sarcoplasmic reticulum fraction was isolated from malignant hyperthermia and control muscle using differential and density-gradient centrifugation. Prior to onset of malignant hyperthermia, calcium-sequestering activity (Vmax at 37 degrees C, mumol calcium/mg/min) was twofold increased in malignant hyperthermia sarcoplasmic reticulum compared to control sarcoplasmic reticulum (1.96 +/- 0.50 versus 4.00 +/- 0.87, P less than 0.01), although thermodynamic and kinetic properties of this activity were otherwise indistinguishable between groups. This increased activity of the malignant hyperthermia sarcoplasmic reticulum fraction was associated with twofold increased concentration of Ca-ATPase and calsequestrin protein. When a malignant hyperthermia-reaction developed, calcium-uptake was depressed to less than 5% of control values. These data indicate that malignant hyperthermia is not initiated due to a defect in the calcium-sequestration mechanism, however, loss of calcium-uptake activity occurring after the onset of malignant hyperthermia might result in the propagation and irreversibility of the malignant hyperthermia reaction. Images Fig. 1. PMID:3742368

  4. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

    PubMed Central

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

    2015-01-01

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

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

    PubMed Central

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

    2016-01-01

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

  6. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects. PMID:23746561

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

    PubMed

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

    1995-02-10

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

  8. Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.

    PubMed

    Hunter, A J; Morris, T A; Jin, B; Saint, C P; Kelly, J M

    2013-09-01

    Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes. PMID:23835170

  9. High phosphorylase activity is correlated with increased potato minituber formation and starch content during extended clinorotation

    NASA Astrophysics Data System (ADS)

    Nedukha, O. M.; Schnyukova, E. I.; Leach, J. E.

    2003-05-01

    The major purpose of these experiments were to investigate growth of potato storage organs and starch synthesis in minitubers at slow horizontal clinorotation (2 rpm), which partly mimics microgravity, and a secondary goal was to study the activity and localization of phosphorylase (EC 2.4.1.1) in storage parenchyma under these conditions. Miniplants of Solanum tuberosum L. (cv Adreta) were grown in culture for 30 days for both the vertical control and the horizontal clinorotation. During long-term clinorotation, an acceleration of minituber formation, and an increase of amyloplast number and size in storage parenchyma cells, as well as increased starch content, was observed in the minitubers. The differences among cytochemical reaction intensity, activity of phosphorylase, and carbohydrate content in storage parenchyma cells of minitubers grown in a horizontal clinostat were established by electron-cytochemical and biochemical methods. It is shown that high phosphorylase activity is correlated with increased starch content during extended clinorotation. The results demonstrate the increase in carbohydrate metabolism and possible accelerated growth of storage organs under the influence of microgravity, as mimicked by clinorotation; therefore, clinorotation can be used as a basis for future studies on mechanisms of starch synthesis under microgravity.

  10. Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

    PubMed Central

    Hottz, Eugenio D.; Lopes, Juliana F.; Freitas, Carla; Valls-de-Souza, Rogério; Oliveira, Marcus F.; Bozza, Marcelo T.; Da Poian, Andrea T.; Weyrich, Andrew S.; Zimmerman, Guy A.

    2013-01-01

    Dengue is the most frequent hemorrhagic viral disease and re-emergent infection in the world. Although thrombocytopenia is characteristically observed in mild and severe forms of dengue, the role of platelet activation in dengue pathogenesis has not been fully elucidated. We hypothesize that platelets have major roles in inflammatory amplification and increased vascular permeability during severe forms of dengue. Here we investigate interleukin (IL)-1β synthesis, processing, and secretion in platelets during dengue virus (DV) infection and potential contribution of these events to endothelial permeability during infection. We observed increased expression of IL-1β in platelets and platelet-derived microparticles from patients with dengue or after platelet exposure to DV in vitro. We demonstrated that DV infection leads to assembly of nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasomes, activation of caspase-1, and caspase-1–dependent IL-1β secretion. Our findings also indicate that platelet-derived IL-1β is chiefly released in microparticles through mechanisms dependent on mitochondrial reactive oxygen species–triggered NLRP3 inflammasomes. Inflammasome activation and platelet shedding of IL-1β–rich microparticles correlated with signs of increased vascular permeability. Moreover, microparticles from DV-stimulated platelets induced enhanced permeability in vitro in an IL-1–dependent manner. Our findings provide new evidence that platelets contribute to increased vascular permeability in DV infection by inflammasome-dependent release of IL-1β. PMID:24009231

  11. Deletion of creB in Aspergillus oryzae Increases Secreted Hydrolytic Enzyme Activity

    PubMed Central

    Hunter, A. J.; Morris, T. A.; Jin, B.; Saint, C. P.

    2013-01-01

    Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes. PMID:23835170

  12. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes

    PubMed Central

    Calderon-Dominguez, María; Sebastián, David; Fucho, Raquel; Weber, Minéia; Mir, Joan F.; García-Casarrubios, Ester; Obregón, María Jesús; Zorzano, Antonio; Valverde, Ángela M.; Serra, Dolors

    2016-01-01

    The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders. PMID:27438137

  13. Aversive emotional interference impacts behavior and prefronto-striatal activity during increasing attentional control

    PubMed Central

    Papazacharias, Apostolos; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Di Giorgio, Annabella; Lo Bianco, Luciana; Quarto, Tiziana; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Caforio, Grazia; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

    2015-01-01

    Earlier studies have demonstrated that emotional stimulation modulates attentional processing during goal-directed behavior and related activity of a brain network including the inferior frontal gyrus (IFG) and the caudate nucleus. However, it is not clear how emotional interference modulates behavior and brain physiology during variation in attentional control, a relevant question for everyday life situations in which both emotional stimuli and cognitive load vary. The aim of this study was to investigate the impact of negative emotions on behavior and activity in IFG and caudate nucleus during increasing levels of attentional control. Twenty two healthy subjects underwent event-related functional magnetic resonance imaging while performing a task in which neutral or fearful facial expressions were displayed before stimuli eliciting increasing levels of attentional control processing. Results indicated slower reaction time (RT) and greater right IFG activity when fearful compared with neutral facial expressions preceded the low level of attentional control. On the other hand, fearful facial expressions preceding the intermediate level of attentional control elicited faster behavioral responses and greater activity in the right and left sides of the caudate. Finally, correlation analysis indicated a relationship between behavioral correlates of attentional control after emotional interference and right IFG activity. All together, these results suggest that the impact of negative emotions on attentional processing is differentially elicited at the behavioral and physiological levels as a function of cognitive load. PMID:25954172

  14. Magnesium ions increase the activity of Bacillus deramificans pullulanase expressed by Brevibacillus choshinensis.

    PubMed

    Zou, Chun; Duan, Xuguo; Wu, Jing

    2016-08-01

    Addition of MgCl2 to the culture medium has been found to dramatically increase the activity of Bacillus deramificans pullulanase expressed by Brevibacillus choshinensis. The specific activity of the pullulanase obtained from medium supplemented with MgCl2 was also higher than that obtained in culture medium without added magnesium ions. In this work, the mechanism of this increase was studied. When cultured in medium without added magnesium ions, B. choshinensis mainly produced a thermolabile, inactive form of pullulanase. The addition of magnesium ions led to the production of a thermostable, active form of pullulanase. Circular dichroism assays revealed considerable differences in secondary structure between the active and inactive pullulanase forms. Transmission electron microscopy suggested that magnesium ion addition inhibits the shedding of cell wall protein (HWP) layers from the cell surface. Quantitative real-time PCR showed that magnesium ion addition represses transcription of HWP. Because the pullulanase gene and HWP have identical promoters, pullulanase gene transcription was also inhibited. These results suggest that when pullulanase is expressed slowly, it tends to fold into an active form. PMID:27026175

  15. Aversive emotional interference impacts behavior and prefronto-striatal activity during increasing attentional control.

    PubMed

    Papazacharias, Apostolos; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Di Giorgio, Annabella; Lo Bianco, Luciana; Quarto, Tiziana; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Caforio, Grazia; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

    2015-01-01

    Earlier studies have demonstrated that emotional stimulation modulates attentional processing during goal-directed behavior and related activity of a brain network including the inferior frontal gyrus (IFG) and the caudate nucleus. However, it is not clear how emotional interference modulates behavior and brain physiology during variation in attentional control, a relevant question for everyday life situations in which both emotional stimuli and cognitive load vary. The aim of this study was to investigate the impact of negative emotions on behavior and activity in IFG and caudate nucleus during increasing levels of attentional control. Twenty two healthy subjects underwent event-related functional magnetic resonance imaging while performing a task in which neutral or fearful facial expressions were displayed before stimuli eliciting increasing levels of attentional control processing. Results indicated slower reaction time (RT) and greater right IFG activity when fearful compared with neutral facial expressions preceded the low level of attentional control. On the other hand, fearful facial expressions preceding the intermediate level of attentional control elicited faster behavioral responses and greater activity in the right and left sides of the caudate. Finally, correlation analysis indicated a relationship between behavioral correlates of attentional control after emotional interference and right IFG activity. All together, these results suggest that the impact of negative emotions on attentional processing is differentially elicited at the behavioral and physiological levels as a function of cognitive load. PMID:25954172

  16. Activation of mitochondrial calpain and increased cardiac injury: beyond AIF release.

    PubMed

    Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J; Chen, Qun

    2016-02-01

    Calpain 1 (CPN1) is a ubiquitous cysteine protease that exists in both cytosol and cardiac mitochondria. Mitochondrial CPN1 (mit-CPN1) is located in the intermembrane space and matrix. Activation of mit-CPN1 within the intermembrane space increases cardiac injury by releasing apoptosis-inducing factor from mitochondria during ischemia-reperfusion (IR). We asked if activation of mit-CPN1 is involved in mitochondrial injury during IR. MDL-28170 (MDL) was used to inhibit CPN1 in buffer-perfused hearts following 25-min ischemia and 30-min reperfusion. MDL treatment decreased the release of lactate dehydrogenase into coronary effluent compared with untreated hearts, indicating that inhibition of CPN1 decreases cardiac injury. MDL also prevented the cleavage of spectrin (a substrate of CPN1) in cytosol during IR, supporting that MDL treatment decreased cytosolic calpain activation. In addition, MDL markedly improved calcium retention capacity compared with untreated heart, suggesting that MDL treatment decreases mitochondrial permeability transition pore opening. In addition, we found that IR led to decreased complex I activity, whereas inhibition of mit-CPN1 using MDL protected complex I. Pyruvate dehydrogenase content was decreased following IR. However, pyruvate dehydrogenase content was preserved in MDL-treated mitochondria. Taken together, MDL treatment decreased cardiac injury during IR by inhibiting both cytosolic and mit-CPN1. Activation of mit-CPN1 increases cardiac injury during IR by sensitizing mitochondrial permeability transition pore opening and impairing mitochondrial metabolism through damage of complex I. PMID:26637561

  17. 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

  18. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils

    SciTech Connect

    Traynor-Kaplan, A.E.; Thompson, B.L.; Harris, A.L.; Taylor, P.; Omann, G.M.; Sklar, L.A. )

    1989-09-15

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation.

  19. Increased Feeding Speed Is Associated with Higher Subsequent Sympathetic Activity in Dogs.

    PubMed

    Ohtani, Nobuyo; Okamoto, Yuta; Tateishi, Kanako; Uchiyama, Hidehiko; Ohta, Mitsuaki

    2015-01-01

    Although the domestication process has altered the feeding behavior of dogs, some breeds still demonstrate a remarkable ability to gorge, and will eat exceptionally large quantities of food whenever it is available. Lesions in the ventromedial hypothalamus increase appetite and lead to obesity, suggesting that the autonomic nervous system plays an important role in feeding. Focusing on the autonomic activities closely involved in food intake, we investigated sympathetic activities before and after feeding in dogs. The subjects were 56 healthy dogs of 21 different breeds (29 males and 27 females). Based on feeding habits, the 56 dogs were divided into three groups: Fast (n = 19), Slow (n = 24) and Leftover (n = 13). The feeding speed and the amount of food per mouthful of the Fast dogs were significantly greater than those of the Slow and the Leftover dogs. The plasma norepinephrine level in dogs of the Fast group was significantly increased after feeding, while those in the Slow and Leftover groups were significantly decreased after feeding, compared with the pre-feeding concentrations. The low frequency/high frequency ratio of heart rate variability is a good indicator of sympathetic activity and was also significantly higher in the Fast group than in the other groups. Delayed feeding using automatic feeding equipment decreased the plasma norepinephrine concentration and low frequency/high frequency ratio observed after feeding in dogs of the Fast group. In conclusion, dogs eating rapidly with less chewing, which indicates increased sympathetic activity during feeding, may benefit from delayed feeding. The slow eating may activate the parasympathetic nervous system after feeding, which could enhance the activity of the digestive system. PMID:26569112

  20. Increased RNA-Induced Silencing Complex (RISC) Activity Contributes to Hepatocellular Carcinoma

    PubMed Central

    Yoo, Byoung Kwon; Santhekadur, Prasanna K.; Gredler, Rachel; Chen, Dong; Emdad, Luni; Bhutia, Sujit; Pannell, Lewis; Fisher, Paul B.; Sarkar, Devanand

    2011-01-01

    There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and co-immunoprecipitation followed by mass spectrometry we identified Staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Co-immunoprecipitation and co-localization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating siRNA and miRNA-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ∼74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor mRNAs that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo thus revealing a potential role of SND1 in hepatocarcinogenesis. Conclusion We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC. PMID:21520169

  1. Increased Feeding Speed Is Associated with Higher Subsequent Sympathetic Activity in Dogs

    PubMed Central

    Ohtani, Nobuyo; Okamoto, Yuta; Tateishi, Kanako; Uchiyama, Hidehiko; Ohta, Mitsuaki

    2015-01-01

    Although the domestication process has altered the feeding behavior of dogs, some breeds still demonstrate a remarkable ability to gorge, and will eat exceptionally large quantities of food whenever it is available. Lesions in the ventromedial hypothalamus increase appetite and lead to obesity, suggesting that the autonomic nervous system plays an important role in feeding. Focusing on the autonomic activities closely involved in food intake, we investigated sympathetic activities before and after feeding in dogs. The subjects were 56 healthy dogs of 21 different breeds (29 males and 27 females). Based on feeding habits, the 56 dogs were divided into three groups: Fast (n = 19), Slow (n = 24) and Leftover (n = 13). The feeding speed and the amount of food per mouthful of the Fast dogs were significantly greater than those of the Slow and the Leftover dogs. The plasma norepinephrine level in dogs of the Fast group was significantly increased after feeding, while those in the Slow and Leftover groups were significantly decreased after feeding, compared with the pre-feeding concentrations. The low frequency/high frequency ratio of heart rate variability is a good indicator of sympathetic activity and was also significantly higher in the Fast group than in the other groups. Delayed feeding using automatic feeding equipment decreased the plasma norepinephrine concentration and low frequency/high frequency ratio observed after feeding in dogs of the Fast group. In conclusion, dogs eating rapidly with less chewing, which indicates increased sympathetic activity during feeding, may benefit from delayed feeding. The slow eating may activate the parasympathetic nervous system after feeding, which could enhance the activity of the digestive system. PMID:26569112

  2. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils.

    PubMed

    Traynor-Kaplan, A E; Thompson, B L; Harris, A L; Taylor, P; Omann, G M; Sklar, L A

    1989-09-15

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation. PMID:2549071

  3. The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity

    PubMed Central

    Park, Hyo-Jin; Ran, Yong; Jung, Joo In; Holmes, Oliver; Price, Ashleigh R; Smithson, Lisa; Ceballos-Diaz, Carolina; Han, Chul; Wolfe, Michael S; Daaka, Yehia; Ryabinin, Andrey E; Kim, Seong-Hun; Hauger, Richard L; Golde, Todd E; Felsenstein, Kevin M

    2015-01-01

    The biological underpinnings linking stress to Alzheimer's disease (AD) risk are poorly understood. We investigated how corticotrophin releasing factor (CRF), a critical stress response mediator, influences amyloid-β (Aβ) production. In cells, CRF treatment increases Aβ production and triggers CRF receptor 1 (CRFR1) and γ-secretase internalization. Co-immunoprecipitation studies establish that γ-secretase associates with CRFR1; this is mediated by β-arrestin binding motifs. Additionally, CRFR1 and γ-secretase co-localize in lipid raft fractions, with increased γ-secretase accumulation upon CRF treatment. CRF treatment also increases γ-secretase activityin vitro, revealing a second, receptor-independent mechanism of action. CRF is the first endogenous neuropeptide that can be shown to directly modulate γ-secretase activity. Unexpectedly, CRFR1 antagonists also increased Aβ. These data collectively link CRF to increased Aβ through γ-secretase and provide mechanistic insight into how stress may increase AD risk. They also suggest that direct targeting of CRF might be necessary to effectively modulate this pathway for therapeutic benefit in AD, as CRFR1 antagonists increase Aβ and in some cases preferentially increase Aβ42 via complex effects on γ-secretase. PMID:25964433

  4. Cyclothiazide-induced persistent increase in respiratory-related activity in vitro

    PubMed Central

    Babiec, Walter E; Faull, Kym F; Feldman, Jack L

    2012-01-01

    Hypoglossal (XII) motoneurons (MNs) innervate the genioglossus muscle of the tongue, which plays an important role in maintaining upper airway patency, particularly during sleep, and modulating upper airway resistance. Discovering methods for inducing long-term increases in genioglossal motoneuronal excitability to AMPA-mediated drive may help in the development of therapeutics for upper airway motor disorders such as obstructive sleep apnoea. We show that the diuretic, anti-hypertensive, AMPA receptor modulator cyclothiazide (CTZ) induces a profound and long-lasting increase in the amplitude of respiratory-related XII nerve activity in rhythmically active neonatal rat medullary slices. Treatment of the slice with CTZ (90 μm) for 1 h increased the integrated XII (∫XII) nerve burst amplitude to 262 ± 23% of pre-treatment control at 1 h post-treatment; much of this increase lasted at least 12 h. The amount of CTZ-induced facilitation (CIF) was dependent upon both CTZ dose and exposure time and was accompanied by a long-lasting increase in endogenous AMPA-mediated drive currents to XII MNs. CIF, however, is not a form of plasticity and does not depend on AMPA or NMDA receptor activation for its induction. Nor does it depend on coincident protein kinase A or C activity. Rather, measurement of mEPSCs along with mass spectrometric analysis of CTZ-treated slices indicates that the cause is prolonged bioavailability of CTZ. These results illustrate a latent residual capacity for potentiating AMPA-mediated inspiratory drive to XII MNs that might be applied to the treatment of upper airway motor deficits. PMID:22753547

  5. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    SciTech Connect

    O'Toole, Timothy E. Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca{sup 2+}]{sub i}), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca{sup 2+}]{sub I} with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca{sup 2+}]{sub I}, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  6. Overexpression of α-synuclein simultaneously increases glutamate NMDA receptor phosphorylation and reduces glucocerebrosidase activity.

    PubMed

    Yang, Junfeng; Hertz, Ellen; Zhang, Xiaoqun; Leinartaité, Lina; Lundius, Ebba Gregorsson; Li, Jie; Svenningsson, Per

    2016-01-12

    Progressive accumulation of α-synuclein (α-syn)-containing protein aggregates throughout the nervous system is a pathological hallmark of Parkinson's disease (PD). The mechanisms whereby α-syn exerts neurodegeneration remain to be fully understood. Here we show that overexpression of α-syn in transgenic mice leads to increased phosphorylation of glutamate NMDA receptor (NMDAR) subunits NR1 and NR2B in substantia nigra and striatum as well as reduced glucocerebrosidase (GCase) levels. Similarly, molecular studies performed in mouse N2A cells stably overexpressing human α-syn ((α-syn)N2A) showed that phosphorylation states of the same NMDAR subunits were increased, whereas GCase levels and lysosomal GCase activity were reduced. (α-syn)N2A cells showed an increased sensitivity to neurotoxicity towards 6-hydroxydopamine and NMDA. However, wildtype N2A, but not (α-syn)N2A cells, showed a further reduction in viability when co-incubated with 6-hydroxydopamine and the lysosomal inhibitors NH4Cl and leupeptin, suggesting that α-syn per se perturbs lysosomal functions. NMDA treatment reduced lysosomal GCase activity to the same extent in (α-syn)N2A cells as in wildtype N2A cells, indicating that the α-syn-dependent difference in NMDA neurotoxicity is unrelated to an altered GCase activity. Nevertheless, these data provide molecular evidence that overexpression of α-syn simultaneously induces two potential neurotoxic hits by increasing glutamate NMDA receptor phosphorylation, consistent with increased NMDA receptors functionality, and reducing GCase activity. PMID:26610904

  7. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

    PubMed Central

    2012-01-01

    Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells

  8. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen

    PubMed Central

    Shi, Zhigang; Brooks, Virginia L

    2015-01-01

    Key points Leptin increases sympathetic nerve activity (SNA) in males, which contributes to obesity-induced hypertension; however, whether leptin is equally effective in females is unknown. We report that leptin does increase SNA and heart rate in female rats; however, for lumbar and renal SNA, this action is only evident in pro-oestrus and in oestrogen-treated ovariectomized rats, but not in ovariectomized or dioestrus rats. Leptin increases SNA and heart rate similarly in male and pro-oestrus female rats; however, leptin increases arterial pressure only in males. Blockade of MC3/4 receptors in the paraventricular nucleus (PVN) with SHU9119 decreases SNA in leptin-treated pro-oestrus rats, suggesting that leptin increases SNA in part by increasing α-melanocyte-stimulating hormone drive of PVN presympathetic neurons. Our data establish sex differences in leptin's effects to increase SNA and arterial pressure, which emphasizes the need for enhanced recognition and investigation of sex differences in obesity-induced sympathoexcitation and hypertension. Abstract Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR

  9. Increased Risk of Active Tuberculosis following Acute Kidney Injury: A Nationwide, Population-Based Study

    PubMed Central

    Chang, Chia-Hsui; Huang, Hui-Yu; Huang, Tao-Min; Lai, Chun-Fu; Lin, Meng-Chun; Ko, Wen-Je; Wu, Kwan-Dun; Yu, Chong-Jen; Shu, Chin-Chung; Lee, Chih-Hsin; Wang, Jann-Yuan

    2013-01-01

    Background Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited. Methods This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999–2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization. Results Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032). Conclusions AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB. PMID:23936044

  10. Histone deacetylase inhibitors increase glucocerebrosidase activity in Gaucher disease by modulation of molecular chaperones

    PubMed Central

    Yang, Chunzhang; Rahimpour, Shervin; Lu, Jie; Pacak, Karel; Ikejiri, Barbara; Brady, Roscoe O.; Zhuang, Zhengping

    2013-01-01

    Gaucher disease is caused by mutations of the GBA gene that encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA mutations often result in protein misfolding and premature degradation, but usually exert less effect on catalytic activity. In this study, we identified the molecular mechanism by which histone deacetylase inhibitors increase the quantity and activity of GCase. Specifically, these inhibitors limit the deacetylation of heat shock protein 90, resulting in less recognition of the mutant peptide and GCase degradation. These findings provide insight into a possible therapeutic strategy for Gaucher disease and other genetic disorders by modifying molecular chaperone and protein degradation pathways. PMID:23277556

  11. Term myometrium is characterized by increased activating epigenetic modifications at the progesterone receptor-A promoter.

    PubMed

    Chai, S Y; Smith, R; Zakar, T; Mitchell, C; Madsen, G

    2012-08-01

    Term human myometrial expression of progesterone receptor (PR)-A is increased relative to PR-B, and as PR-A is a repressor of progesterone action mediated through PR-B, this increase may mediate the withdrawal of progesterone action and precipitate the onset of labour. PR-A and PR-B expression is regulated by two separate promoters of the PR gene. We hypothesized that epigenetic histone modifications at the two promoters contribute to the labour-associated regulation of PR-A and PR-B expression in term myometrium. PR total, PR-B and PR-A mRNA levels were determined using quantitative real-time PCR, and chromatin immunoprecipitation was used to determine the levels of activating and repressive histone modifications at the PR-A and PR-B promoters in human myometrial samples not in labour (n = 4) and in labour (n = 4). Chromatin extracts were immunoprecipitated with antibodies against activating (histone H3 and H4 acetylation and histone H3 lysine 4 trimethylation), and repressive (histone H3 lysine 9 trimethylation, histone H3 lysine 27 trimethylation and asymmetrical histone H3 arginine 2 dimethylation) histone modifications. PR-A mRNA levels increased during labour, while PR-B mRNA levels remained constant resulting in an increase of PR-A/PR-B mRNA ratio, as expected. Regardless of labour status, significantly higher levels of the activating histone modifications were found at the PR-A promoter compared with the PR-B promoter (P <0.001). H3K4me3 increased significantly at both promoters with labour onset (P =0.001). Low levels of the repressive histone modifications were also present at both promoters, with no labour-associated changes observed. Our data indicate that the PR-A promoter is epigenetically marked for activation in term myometrium more extensively than the PR-B promoter, and that labour is associated with an increase in H3K4me3 activating modification, consistent with the previously described increase in PR protein at this time. PMID:22369759

  12. Increased oxygen consumption following activation of brain: theoretical footnotes using spectroscopic data from barrel cortex.

    PubMed

    Mayhew, J; Johnston, D; Martindale, J; Jones, M; Berwick, J; Zheng, Y

    2001-06-01

    Optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) data sequences from anesthetized rats were used to determine the relationship between changes in oxy-and deoxygenated hemoglobin concentration and changes in blood volume and flow in the presence and absence of stimulation. The data from Jones et al. (accompanying paper) were used to explore the differences between two theoretical models of flow activation coupling. The essential difference between the two models is the extension of the model of Buxton and Frank by Hyder et al. (1998, J. Appl. Physiol. 85: 554--564) to incorporate change in capillary diffusivity coupled to flow. In both models activation-increased flow changes increase oxygen transport from the capillary; however, in Hyder et al.'s model the diffusivity of the capillary itself is increased. Hyder et al. proposed a parameter (Omega), a scaling "constant" linking increased blood flow and oxygen "diffusivity" in the capillary bed. Thus, in Buxton and Frank's theory, Omega = 0; i.e., there are no changes in diffusivity. In Hyder et al.'s theory, 0 < Omega < 1, and changes in diffusivity are assumed to be linearly related to flow changes. We elaborate the theoretical position of both models to show that, in principle, the different predictions from the two theories can be evaluated using optical imaging spectroscopy data. We find that both theoretical positions have limitations when applied to data from brief stimulation and when applied to data from mild hypercapnia. In summary, the analysis showed that although Hyder et al.'s proposal that diffusivity increased during activation did occur; it was shown to arise from an implementation of Buxton and Frank's theory under episodes of brief stimulation. The results also showed that the scaling parameter Omega is not a constant as the Hyder et al. model entails but in fact varies over the time course of the flow changes. Data from experiments in which mild hypercapnia was administered also

  13. Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress.

    PubMed

    Vitzthum, Constanze; Clauss, Wolfgang G; Fronius, Martin

    2015-11-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-) channel that is essential for electrolyte and fluid homeostasis. Preliminary evidence indicates that CFTR is a mechanosensitive channel. In lung epithelia, CFTR is exposed to different mechanical forces such as shear stress (Ss) and membrane distention. The present study questioned whether Ss and/or stretch influence CFTR activity (wild type, ∆F508, G551D). Human CFTR (hCFTR) was heterologously expressed in Xenopus oocytes and the response to the mechanical stimulus and forskolin/IBMX (FI) was measured by two-electrode voltage-clamp experiments. Ss had no influence on hCFTR activity. Injection of an intracellular analogous solution to increase cell volume alone did not affect hCFTR activity. However, hCFTR activity was augmented by injection after pre-stimulation with FI. The response to injection was similar in channels carrying the common mutations ∆F508 and G551D compared to wild type hCFTR. Stretch-induced CFTR activation was further assessed in Ussing chamber measurements using Xenopus lung preparations. Under control conditions increased hydrostatic pressure (HP) decreased the measured ion current including activation of a Cl(-) secretion that was unmasked by the CFTR inhibitor GlyH-101. These data demonstrate activation of CFTR in vitro and in a native pulmonary epithelium in response to mechanical stress. Mechanosensitive regulation of CFTR is highly relevant for pulmonary physiology that relies on ion transport processes facilitated by pulmonary epithelial cells. PMID:26357939

  14. Meta-analysis of internet-delivered interventions to increase physical activity levels

    PubMed Central

    2012-01-01

    Many internet-delivered physical activity behaviour change programs have been developed and evaluated. However, further evidence is required to ascertain the overall effectiveness of such interventions. The objective of the present review was to evaluate the effectiveness of internet-delivered interventions to increase physical activity, whilst also examining the effect of intervention moderators. A systematic search strategy identified relevant studies published in the English-language from Pubmed, Proquest, Scopus, PsychINFO, CINHAL, and Sport Discuss (January 1990 – June 2011). Eligible studies were required to include an internet-delivered intervention, target an adult population, measure and target physical activity as an outcome variable, and include a comparison group that did not receive internet-delivered materials. Studies were coded independently by two investigators. Overall effect sizes were combined based on the fixed effect model. Homogeneity and subsequent exploratory moderator analysis was undertaken. A total of 34 articles were identified for inclusion. The overall mean effect of internet-delivered interventions on physical activity was d = 0.14 (p = 0.00). Fixed-effect analysis revealed significant heterogeneity across studies (Q = 73.75; p = 0.00). Moderating variables such as larger sample size, screening for baseline physical activity levels and the inclusion of educational components significantly increased intervention effectiveness. Results of the meta-analysis support the delivery of internet-delivered interventions in producing positive changes in physical activity, however effect sizes were small. The ability of internet-delivered interventions to produce meaningful change in long-term physical activity remains unclear. PMID:22546283

  15. ATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination.

    PubMed

    Khair, Lyne; Guikema, Jeroen E J; Linehan, Erin K; Ucher, Anna J; Leus, Niek G J; Ogilvie, Colin; Lou, Zhenkun; Schrader, Carol E; Stavnezer, Janet

    2014-05-15

    Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm(-/-) cells Sμ DSBs are increased, whereas DSBs in downstream Sγ regions are decreased. We also find that mutations in the unrearranged Sγ3 segment are reduced in atm(-/-) cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm(-/-) cells Sμ DSBs accumulate as they lack a recombination partner. PMID:24729610

  16. Increased oxidative activity in human blood neutrophils and monocytes after spinal cord injury.

    PubMed

    Bao, Feng; Bailey, Christopher S; Gurr, Kevin R; Bailey, Stewart I; Rosas-Arellano, M Patricia; Dekaban, Gregory A; Weaver, Lynne C

    2009-02-01

    Traumatic injury can cause a systemic inflammatory response, increasing oxidative activity of circulating leukocytes and potentially exacerbating the original injury, as well as causing damage to initially unaffected organs. Although the importance of intraspinal inflammation after human spinal cord injury is appreciated, the role of the systemic inflammatory response to this injury is not widely recognised. We investigated oxidative activity of blood leukocytes from nine cord-injured subjects and six trauma controls (bone fractures without CNS injury) at 6 h-2 weeks after injury, comparing values to those of ten uninjured subjects. Neutrophil and monocyte free radical production, evaluated by flow cytometry, increased significantly more in cord injury subjects than in trauma controls (6-fold vs 50% increases). In leukocyte homogenates, the concentration of free radicals increased significantly more in cord injury subjects (2-fold) than in the trauma controls (1.6-fold) as did activity of myeloperoxidase (2.3-fold vs. 1.7-fold). Moreover, in homogenates and blood smears, expression of the NADPH oxidase subunit gp91(phox) and of the oxidative enzyme, inducible nitric oxide synthetase was 20-25% greater in cord injury subjects than in trauma controls. Expression of the pro-inflammatory transcription factor NF-kappaB and of cyclooxygenase-2 increased similarly after both injuries. Finally, aldehyde products of tissue-damaging lipid peroxidation also increased significantly more in the plasma of spinal cord injury subjects than in trauma controls (2.6 fold vs. 1.9-fold). Spinal cord injury causes a particularly intense systemic inflammatory response. Limiting this response briefly after cord injury should protect the spinal cord and tissues/organs outside the CNS from secondary damage. PMID:19056384

  17. ALDH2 Activator Inhibits Increased Myocardial Infarction Injury by Nitroglycerin Tolerance

    PubMed Central

    Sun, Lihan; Ferreira, Julio Cesar Batista; Mochly-Rosen, Daria

    2012-01-01

    Nitroglycerin, which helps impaired cardiac function as it is converted to nitric oxide, is used worldwide to treat patients with various ischemic and congestive cardiac diseases, including angina pectoris. Nevertheless, after continuous treatment, the benefits of nitroglycerin are limited by the development of tolerance to the drug. Nitroglycerin tolerance is a result of inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme essential for cardioprotection in animals subjected to myocardial infarction (MI). Here we tested the hypothesis that the tolerance that develops as a result of sustained nitroglycerin treatment increases cardiac injury by subsequent MI. In a rat model of MI, 16 hours of prior, sustained nitroglycerin treatment (7.2 mg/kg/day) resulted in infarcts that were twice as large as those in untreated control animals and in diminished cardiac function at 3 days and 2 weeks after the MI. We also sought to identify a potential treatment to protect against this increased cardiac damage. Nitroglycerin inhibited ALDH2 activity in vitro, an effect that was blocked by Alda-1, an activator of ALDH2. Co-administration of Alda-1 (16 mg/kg/day) with the nitroglycerin prevented the nitroglycerin-induced increase in cardiac dysfunction after MI in rats, at least in part by enhancing metabolism of reactive aldehyde adducts that impair normal protein functions. If our animal studies showing that nitroglycerin tolerance increases cardiac injury upon ischemic insult are corroborated in humans, activators of ALDH2 such as Alda-1 may help to protect MI patients from this nitroglycerin-induced increase in cardiac injury, while maintaining the cardiac benefits of the increased nitric oxide concentrations produced by nitroglycerin. PMID:22049071

  18. Circulating Myeloid-Derived Suppressor Cells Are Increased and Activated in Pulmonary Hypertension

    PubMed Central

    Nguyen, Cecilia M.; Belchenko, Dmitry D.; Colvin, Kelley L.; Takatsuki, Shinichi; Ivy, D. Dunbar; Stenmark, Kurt R.

    2012-01-01

    Background: Myeloid-derived suppressor cells (MDSCs) are increased in inflammatory and autoimmune disorders and orchestrate immune cell responses therein. Pulmonary hypertension (PH) is associated with inflammation, autoimmunity, and lung vascular remodeling. Immature myeloid cells are found in the lungs of humans and animals with PH, and we hypothesized that they would be increased in the blood of patients with PH compared with control subjects. Methods: Twenty-six children with PH and 10 undergoing cardiac catheterization for arrhythmia ablation were studied. Five milliliters of fresh blood were analyzed using flow cytometry. Results were confirmed using magnetic bead sorting and immunofluorescence, while quantitative polymerase chain reaction and intracellular urea concentration assays were used as measures of MDSC arginase-1 activation. Results: Flow cytometry demonstrated enrichment of circulating MDSCs among patients with PH (n = 26; mean, 0.271 × 106 cells/mL ± 0.17; 1.86% of CD45+ population ± 1.51) compared with control subjects (n = 10; mean, 0.176 × 106 cells/mL ± 0.05; 0.57% of CD45+ population ± 0.29; P < .05). Higher numbers of circulating MDSCs correlated to increasing mean pulmonary artery pressure (r = 0.510, P < .05). Among patients with PH, female patients had a twofold increase in MDSCs compared with male patients. Immunofluorescence analysis confirmed the results of flow cytometry. Quantitative reverse transcription polymerase chain reaction assay results for arginase-1 and measurement of intracellular urea concentration revealed increased activity of MDSCs from patients with PH compared with control subjects. Conclusions: Circulating activated MDSCs are significantly increased in children with PH compared with control subjects. Further investigation of these cells is warranted, and we speculate that they might play significant immunomodulatory roles in the disease pathogenesis of PH. PMID:21940769

  19. Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

    PubMed

    Emelyanova, Larisa; Ashary, Zain; Cosic, Milanka; Negmadjanov, Ulugbek; Ross, Gracious; Rizvi, Farhan; Olet, Susan; Kress, David; Sra, Jasbir; Tajik, A Jamil; Holmuhamedov, Ekhson L; Shi, Yang; Jahangir, Arshad

    2016-07-01

    Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. PMID:27199126

  20. Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning

    PubMed Central

    Eschenko, Oxana; Ramadan, Wiâm; Mölle, Matthias; Born, Jan; Sara, Susan J.

    2008-01-01

    High-frequency oscillations, known as sharp-wave/ripple (SPW-R) complexes occurring in hippocampus during slow-wave sleep (SWS), have been proposed to promote synaptic plasticity necessary for memory consolidation. We recorded sleep for 3 h after rats were trained on an odor-reward association task. Learning resulted in an increased number SPW-Rs during the first hour of post-learning SWS. The magnitude of ripple events and their duration were also elevated for up to 2 h after the newly formed memory. Rats that did not learn the discrimination during the training session did not show any change in SPW-Rs. Successful retrieval from remote memory was likewise accompanied by an increase in SPW-R density and magnitude, relative to the previously recorded baseline, but the effects were much shorter lasting and did not include increases in ripple duration and amplitude. A short-lasting increase of ripple activity was also observed when rats were rewarded for performing a motor component of the task only. There were no increases in ripple activity after habituation to the experimental environment. These experiments show that the characteristics of hippocampal high-frequency oscillations during SWS are affected by prior behavioral experience. Associative learning induces robust and sustained (up to 2 h) changes in several SPW-R characteristics, while after retrieval from remote memory or performance of a well-trained procedural aspect of the task, only transient changes in ripple density were induced. PMID:18385477

  1. Children with High Functioning Autism show increased prefrontal and temporal cortex activity during error monitoring

    PubMed Central

    Goldberg, Melissa C.; Spinelli, Simona; Joel, Suresh; Pekar, James J.; Denckla, Martha B.; Mostofsky, Stewart H.

    2010-01-01

    Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using fMRI in 8–12-year-old children with high-functioning autism (HFA, n=11) and typically developing children (TD, n=15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally-driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes. PMID:21151713

  2. Reduced RKIP enhances nasopharyngeal carcinoma radioresistance by increasing ERK and AKT activity

    PubMed Central

    Yuan, Li; Yi, Hong-Mei; Yi, Hong; Qu, Jia-Quan; Zhu, Jin-Feng; Li, Li-Na; Xiao, Ta; Zheng, Zhen; Lu, Shan-Shan; Xiao, Zhi-Qiang

    2016-01-01

    Raf kinase inhibitory protein (RKIP) functions as a chemo-immunotherapeutic sensitizer of cancers, but regulation of RKIP on tumor radiosensitivity remains largely unexplored. In this study, we investigate the role and mechanism of RKIP in nasopharyngeal carcinoma (NPC) radioresistance. The results showed that RKIP was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its reduction correlated with NPC radioresistance and poor patient survival, and was an independent prognostic factor. In vitro radioresponse assay showed that RKIP overexpression decreased while RKIP knockdown increased NPC cell radioresistance. In the NPC xenografts, RKIP overexpression decreased while RKIP knockdown increased tumor radioresistance. Mechanistically, RKIP reduction promoted NPC cell radioresistance by increasing ERK and AKT activity, and AKT may be a downstream transducer of ERK signaling. Moreover, the levels of phospho-ERK−1/2 and phospho-AKT were increased in the radioresistant NPC tissues compared with radiosensitive ones, and negatively associated with RKIP expression, indicating that RKIP-regulated NPC radioresponse is mediated by ERK and AKT signaling in the clinical samples. Our data demonstrate that RKIP is a critical determinant of NPC radioresponse, and its reduction enhances NPC radioresistance through increasing ERK and AKT signaling activity, highlighting the therapeutic potential of RKIP-ERK-AKT signaling axis in NPC radiosensitization. PMID:26862850

  3. Focused campaign increases activity among participants in Nature's Notebook, a citizen science project

    USGS Publications Warehouse

    Crimmins, Theresa M.; Weltzin, Jake F.; Rosemartin, Alyssa H.; Surina, Echo M.; Marsh, Lee; Denny, Ellen G.

    2014-01-01

    Citizen science projects, which engage non-professional scientists in one or more stages of scientific research, have been gaining popularity; yet maintaining participants’ activity level over time remains a challenge. The objective of this study was to evaluate the potential for a short-term, focused campaign to increase participant activity in a national-scale citizen science program. The campaign that we implemented was designed to answer a compelling scientific question. We invited participants in the phenology-observing program, Nature’s Notebook, to track trees throughout the spring of 2012, to ascertain whether the season arrived as early as the anomalous spring of 2010. Consisting of a series of six electronic newsletters and costing our office slightly more than 1 week of staff resources, our effort was successful; compared with previous years, the number of observations collected in the region where the campaign was run increased by 184%, the number of participants submitting observations increased by 116%, and the number of trees registered increased by 110%. In comparison, these respective metrics grew by 25, 55, and 44%, over previous years, in the southeastern quadrant of the United States, where no such campaign was carried out. The campaign approach we describe here is a model that could be adapted by a wide variety of programs to increase engagement and thereby positively influence participant retention.

  4. Enhanced Enzyme Kinetic Stability by Increasing Rigidity within the Active Site*

    PubMed Central

    Xie, Yuan; An, Jiao; Yang, Guangyu; Wu, Geng; Zhang, Yong; Cui, Li; Feng, Yan

    2014-01-01

    Enzyme stability is an important issue for protein engineers. Understanding how rigidity in the active site affects protein kinetic stability will provide new insight into enzyme stabilization. In this study, we demonstrated enhanced kinetic stability of Candida antarctica lipase B (CalB) by mutating the structurally flexible residues within the active site. Six residues within 10 Å of the catalytic Ser105 residue with a high B factor were selected for iterative saturation mutagenesis. After screening 2200 colonies, we obtained the D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 °C and a 12 °C higher T5015, the temperature at which enzyme activity is reduced to 50% after a 15-min heat treatment. Further characterization showed that global unfolding resistance against both thermal and chemical denaturation also improved. Analysis of the crystal structures of wild-type CalB and the D223G/L278M mutant revealed that the latter formed an extra main chain hydrogen bond network with seven structurally coupled residues within the flexible α10 helix that are primarily involved in forming the active site. Further investigation of the relative B factor profile and molecular dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of the active site residues at high temperature. These results indicate that enhancing the rigidity of the flexible segment within the active site may provide an efficient method for improving enzyme kinetic stability. PMID:24448805

  5. Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity

    PubMed Central

    Schaaf, Bernhard; Liebau, Cornelia; Kurowski, Volkhard; Droemann, Daniel; Dalhoff, Klaus

    2008-01-01

    Background Neutrophil products like matrix metalloproteinases (MMP), involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP). In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S. aureus and pseudomonas species on pulmonary MMPconcentration in human pneumonia. Methods In 37 patients with HAP and 16 controls, MMP-8, MMP-9 and tissue inhibitors of MMP (TIMP) were analysed by ELISA and MMP-9 activity using zymography in bronchoalveolar lavage (BAL). Results MMP-9 activity in mini-BAL was increased in HAP patients versus controls (149 ± 41 vs. 34 ± 11, p < 0.0001). In subgroup analysis, the highest MMP concentrations and activity were seen in patients with high-risk bacteria: patients with high-risk bacteria MMP-9 1168 ± 266 vs. patients with low-risk bacteria 224 ± 119 ng/ml p < 0.0001, MMP-9 gelatinolytic activity 325 ± 106 vs. 67 ± 14, p < 0.0002. In addition, the MMP-8 and MMP-9 concentration was associated with the state of ventilation and systemic inflammatory marker like CRP. Conclusion Pulmonary MMP concentrations and MMP activity are elevated in patients with HAP. This effect is most pronounced in patients with high-risk bacteria. Artificial ventilation may play an additional role in protease activation. PMID:18700005

  6. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

    PubMed Central

    Herms, Albert; Bosch, Marta; Reddy, Babu J.N.; Schieber, Nicole L.; Fajardo, Alba; Rupérez, Celia; Fernández-Vidal, Andrea; Ferguson, Charles; Rentero, Carles; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Gross, Steven P.; Pol, Albert

    2015-01-01

    Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

  7. Downregulation of vitellogenin gene activity increases the gustatory responsiveness of honey bee workers (Apis mellifera)

    PubMed Central

    Amdam, Gro V.; Norberg, Kari; Page, Robert E.; Erber, Joachim; Scheiner, Ricarda

    2008-01-01

    In the honey bee (Apis mellifera), young workers usually perform tasks in the nest while older workers forage in the field. The behavioral shift from nest-task to foraging activity is accompanied by physiological and sensory changes so that foragers can be characterized by a higher juvenile hormone (JH) level, a lower vitellogenin protein titer, and an increased responsiveness to water and sucrose stimuli. JH was hypothesized to be the key mediator of behavioral development, physiology, and sensory sensitivity in honey bee workers. Recent research, however, has shown that JH is controlled by the hemolymph vitellogenin level, which implies that the fat body specific vitellogenin gene can be a key regulator of behavioral change. Here, we show that downregulation of vitellogenin activity by RNA interference (RNAi) causes an increase in the gustatory responsiveness of worker bees. Our observations suggest that vitellogenin is an important regulator of long-term changes in honey bee behavior. PMID:16466813

  8. Synthetic ceramide analogues increase amyloid-β 42 production by modulating γ-secretase activity.

    PubMed

    Takasugi, Nobumasa; Sasaki, Tomoki; Shinohara, Mitsuru; Iwatsubo, Takeshi; Tomita, Taisuke

    2015-02-01

    γ-Secretase cleaves amyloid β-precursor protein (APP) to generate amyloid-β peptide (Aβ), which is a causative molecule of Alzheimer disease (AD). The C-terminal length of Aβ, which is determined by γ-secretase activity, determines the aggregation and deposition profiles of Aβ, thereby affecting the onset of AD. In this study, we found that the synthetic ceramide analogues dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and (1S,2R-d-erythro-2-N-myristoylamino)-1-phenyl-1-propanol (DMAPP) modulated γ-secretase-mediated cleavage to increase Aβ42 production. Unexpectedly, PDMP and DMAPP upregulated Aβ42 production independent of alteration of ceramide metabolism. Our results propose that synthetic ceramide analogues function as novel γ-secretase modulators that increase Aβ42, and this finding might lead to the understanding of the effect of the lipid environment on γ-secretase activity. PMID:25545059

  9. Spectral Analysis of the Signals Associated with Increased Activity in Popocatepetl Volcano April 2012

    NASA Astrophysics Data System (ADS)

    Cuenca, J.

    2013-05-01

    After several decades of being inactive in 1994 had a strong reactivation. Since then he has had long periods where volcanic activity including increased growth and destruction of a dome. In April 2012 Popocatepetl Volcano activity showed an increase in the emission of gas and ash, and Vulcanian type explosions. As a result the National Center for Disaster Prevention (CENAPRED) raised the yellow phase from 2 to 3. Spectrally analyzes seismic activity characteristic of the types of events (explosions, LP, Type-B and tremors) that provides information of the source processes that cause it, despite sustained change reflected by the complexity of the volcanic apparatus, through of: 1) the spectral content of the process provides the source, 2) the spectral ratio H / V, its associated amplification and dominant frequencies, 3) time frequency analysis showing the variation in frequency, 4) the particle motion to analyze its retrograde or prograde acting in a volcanic complex medium. The calculation of H / V was performed by each hour using windows with duration of 80 seconds in the broadband seismic station "Canario" (PPPB). The predominant frequencies of H / V are around 1.4-1.8 Hz to 2.1-2.6 Hz and amplifications from 2.3 to 6.9 times. Analysis of H / V of 48 hours (days 16 and April 17) for the case of 1.4-1.8 Hz was observed: (1) From 0-9 hours there is no amplification. (2) The seismic amplification increases from 10 to 11 hours. (3) A first crisis reaches a maximum at 13 hours with about 6 times of amplification. (4) From 14 to 15 hours there is a strong relaxation of the activity. (5) The activity begins to increase from 16 to 23 hours where it reaches its maximum amplification of almost 7 times. (6) The following two hours and is kept exceeding 6 times of amplification. (7) Then is followed by a decrease to 4 hours on the day 17, from which is maintained at a level variable. (8) At 18 hours of the day 17 grows the amplification at 6.2 times, which conforms a

  10. PPARγ-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages

    PubMed Central

    Xavier, Mariana N.; Winter, Maria G.; Spees, Alanna M.; den Hartigh, Andreas B.; Nguyen, Kim; Roux, Christelle M.; Silva, Teane M. A.; Atluri, Vidya L.; Kerrinnes, Tobias; Keestra, A. Marijke; Monack, Denise M.; Luciw, Paul A.; Eigenheer, Richard A.; Bäumler, Andreas J.; Santos, Renato L.; Tsolis, Renée M.

    2013-01-01

    SUMMARY Eradication of persistent intracellular bacterial pathogens with antibiotic therapy is often slow or incomplete. However, strategies to augment antibiotics are hampered by our poor understanding of the nutritional environment that sustains chronic infection. Here we show that the intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAM), which are more abundant during chronic infection. A metabolic shift induced by peroxisome proliferator activated receptor γ (PPARγ), which increases intracellular glucose availability, is identified as a causal mechanism promoting enhanced bacterial survival in AAM. Glucose uptake was crucial for increased replication of B. abortus in AAM, and chronic infection, as inactivation of the bacterial glucose transporter gluP reduced both intracellular survival in AAM and persistence in mice. Thus, a shift in intracellular nutrient availability induced by PPARγ promotes chronic persistence of B. abortus within AAM and targeting this pathway may aid in eradicating chronic infection. PMID:23954155

  11. PPARγ-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages.

    PubMed

    Xavier, Mariana N; Winter, Maria G; Spees, Alanna M; den Hartigh, Andreas B; Nguyen, Kim; Roux, Christelle M; Silva, Teane M A; Atluri, Vidya L; Kerrinnes, Tobias; Keestra, A Marijke; Monack, Denise M; Luciw, Paul A; Eigenheer, Richard A; Bäumler, Andreas J; Santos, Renato L; Tsolis, Renée M

    2013-08-14

    Eradication of persistent intracellular bacterial pathogens with antibiotic therapy is often slow or incomplete. However, strategies to augment antibiotics are hampered by our poor understanding of the nutritional environment that sustains chronic infection. Here we show that the intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAMs), which are more abundant during chronic infection. A metabolic shift induced by peroxisome proliferator-activated receptor γ (PPARγ), which increases intracellular glucose availability, is identified as a causal mechanism promoting enhanced bacterial survival in AAMs. Glucose uptake was crucial for increased replication of B. abortus in AAMs, and for chronic infection, as inactivation of the bacterial glucose transporter gluP reduced both intracellular survival in AAMs and persistence in mice. Thus, a shift in intracellular nutrient availability induced by PPARγ promotes chronic persistence of B. abortus within AAMs, and targeting this pathway may aid in eradicating chronic infection. PMID:23954155

  12. Synaptic Proteins In Schizophrenia Hippocampus Indicate Increased Neuronal Activity in CA3

    PubMed Central

    Li, Wei; Ghose, Subroto; Gleason, Kelly; Begovic’, Anita; Perez, Jessica; Bartko, John; Russo, Scott; Wagner, Anthony D.; Selemon, Lynn; Tamminga, Carol A.

    2015-01-01

    In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on a model of hippocampal dysfunction in schizophrenic psychosis, we postulated increased NMDA receptor signaling in CA3. Here we demonstrate that the GluN2B-containing NMDA receptors (GluN2B/GluN1) and its associated postsynaptic membrane protein PSD95 are both increased in human hippocampal CA3 from schizophrenia cases, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons show an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. AMPA receptor subunit proteins are not altered in CA3 or CA1 subfields, nor are several additional related signaling proteins. These hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state which may contribute to development of long term potentiation with subsequent stimulation and ‘un-silencing’. These changes are plausibly associated with increased associational activity in CA3, degraded declarative memory function and with psychotic manifestations in schizophrenia. The influence of these hyperactive hippocampal projections onto targets in limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions. PMID:25585032

  13. Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

    PubMed Central

    Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

    2013-01-01

    Background: Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. Methods: The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Results: Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume

  14. Approximate spatial reasoning

    NASA Technical Reports Server (NTRS)

    Dutta, Soumitra

    1988-01-01

    A model for approximate spatial reasoning using fuzzy logic to represent the uncertainty in the environment is presented. Algorithms are developed which can be used to reason about spatial information expressed in the form of approximate linguistic descriptions similar to the kind of spatial information processed by humans. Particular attention is given to static spatial reasoning.

  15. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    SciTech Connect

    Feng, Shan-Li; Sun, Ming-Rui; Li, Ting-Ting; Yin, Xin; Xu, Chang-Qing; Sun, Yi-Hua

    2011-03-11

    Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3

  16. Increased Brain Activation for Dual Tasking with 70-Days Head-Down Bed Rest.

    PubMed

    Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia A; De Dios, Yiri E; Gadd, Nichole E; Wood, Scott J; Riascos, Roy; Kofman, Igor S; Bloomberg, Jacob J; Mulavara, Ajitkumar P; Seidler, Rachael D

    2016-01-01

    Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to simulate the effects of microgravity exposure on human physiology, sensorimotor function, and cognition on Earth. Previous studies have reported that concurrent performance of motor and cognitive tasks can be impaired during space missions. Understanding the consequences of HDBR for neural control of dual tasking may possibly provide insight into neural efficiency during spaceflight. In the current study, we evaluated how dual task performance and the underlying brain activation changed as a function of HDBR. Eighteen healthy men participated in this study. They remained continuously in the 6° head-down tilt position for 70 days. Functional MRI for bimanual finger tapping was acquired during both single task and dual task conditions, and repeated at 7 time points pre-, during- and post-HDBR. Another 12 healthy males participated as controls who did not undergo HDBR. A widely distributed network involving the frontal, parietal, cingulate, temporal, and occipital cortices exhibited increased activation for dual tasking and increased activation differences between dual and single task conditions during HDBR relative to pre- or post-HDBR. This HDBR-related brain activation increase for dual tasking implies that more neurocognitive control is needed for dual task execution during HDBR compared to pre- and post-HDBR. We observed a positive correlation between pre-to-post HDBR changes in dual-task cost of reaction time and pre-to-post HDBR change in dual-task cost of brain activation in several cerebral and cerebellar regions. These findings could be predictive of changes in dual task processing during spaceflight. PMID:27601982

  17. Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects

    PubMed Central

    Ferriero, Rosa; Boutron, Audrey; Brivet, Michele; Kerr, Douglas; Morava, Eva; Rodenburg, Richard J; Bonafé, Luisa; Baumgartner, Matthias R; Anikster, Yair; Braverman, Nancy E; Brunetti-Pierri, Nicola

    2014-01-01

    Objective Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. PDHC deficiency is genetically heterogenous and most patients have defects in the X-linked E1-α gene but defects in the other components of the complex encoded by PDHB, PDHX, DLAT, DLD genes or in the regulatory enzyme encoded by PDP1 have also been found. Phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of pyruvate dehydrogenase kinases and thus, has potential for therapy of patients with PDHC deficiency. In the present study, we investigated response to phenylbutyrate of multiple cell lines harboring all known gene defects resulting in PDHC deficiency. Methods Fibroblasts of patients with PDHC deficiency were studied for their enzyme activity at baseline and following phenylbutyrate incubation. Drug responses were correlated with genotypes and protein levels by Western blotting. Results Large deletions affecting PDHA1 that result in lack of detectable protein were unresponsive to phenylbutyrate, whereas increased PDHC activity was detected in most fibroblasts harboring PDHA1 missense mutations. Mutations affecting the R349-α residue were directed to proteasome degradation and were consistently unresponsive to short-time drug incubation but longer incubation resulted in increased levels of enzyme activity and protein that may be due to an additional effect of phenylbutyrate as a molecular chaperone. Interpretation PDHC enzyme activity was enhanced by phenylbutyrate in cells harboring missense mutations in PDHB, PDHX, DLAT, DLD, and PDP1 genes. In the prospect of a clinical trial, the results of this study may allow prediction of in vivo response in patients with PDHC deficiency harboring a wide spectrum of molecular defects. PMID:25356417

  18. Increased Telomerase Activity and Vitamin D Supplementation in Overweight African Americans

    PubMed Central

    Zhu, Haidong; Guo, Dehuang; Li, Ke; Pedersen-White, Jennifer; Stallmann-Jorgensen, Inger Susanne; Huang, Ying; Parikh, Samip; Liu, Kebin; Dong, Yanbin

    2013-01-01

    Objective We aimed to investigate whether vitamin D supplementation modulates peripheral blood mononuclear cell telomerase activity in overweight African Americans. Design A double blind, randomized, and placebo-controlled clinical trial (#NCT01141192) was recently conducted. Subjects and methods African American adults were randomly assigned to either the placebo, or the vitamin D group (60,000 IU/month [equivalent to ~2,000 IU/day] oral vitamin D3 supplementation). Fresh peripheral blood mononuclear cells (PBMC) were collected from 37 subjects (18 in the placebo group and 19 in the vitamin D group) both at baseline and 16 weeks. PBMC telomerase activity was measured by the telomeric repeat amplification protocol. Results Serum 25 hydroxyvitamin D levels increased from 40.7±15.7 nmol/L at baseline to 48.1±17.5 nmol/L at posttest (p=0.004) in the placebo group, and from 35.4±11.3 nmol/L at baseline to 103.7±31.5 nmol/L posttests (p<0.0001) in the vitamin D group. In the vitamin D group, PBMC telomerase activity increased by 19.2% from baseline (1.56±0.29 AU) to posttest (1.86±0.42 AU, p<0.0001). The significance persisted after controlling for age, sex and body mass index (p=0.039). PBMC telomerase activity in the placebo group did not change from baseline (1.43±0.26 AU) to posttest (1.46±0.27 AU, p=0.157). Conclusion Vitamin D supplementation significantly increased PBMC telomerase activity in overweight African Americans. Our data suggest that vitamin D may improve telomere maintenance and prevent cell senescence and counteract obesity-induced acceleration of cellular aging. PMID:21986705

  19. Increased Brain Activation for Dual Tasking with 70-Days Head-Down Bed Rest

    PubMed Central

    Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia A.; De Dios, Yiri E.; Gadd, Nichole E.; Wood, Scott J.; Riascos, Roy; Kofman, Igor S.; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2016-01-01

    Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to simulate the effects of microgravity exposure on human physiology, sensorimotor function, and cognition on Earth. Previous studies have reported that concurrent performance of motor and cognitive tasks can be impaired during space missions. Understanding the consequences of HDBR for neural control of dual tasking may possibly provide insight into neural efficiency during spaceflight. In the current study, we evaluated how dual task performance and the underlying brain activation changed as a function of HDBR. Eighteen healthy men participated in this study. They remained continuously in the 6° head-down tilt position for 70 days. Functional MRI for bimanual finger tapping was acquired during both single task and dual task conditions, and repeated at 7 time points pre-, during- and post-HDBR. Another 12 healthy males participated as controls who did not undergo HDBR. A widely distributed network involving the frontal, parietal, cingulate, temporal, and occipital cortices exhibited increased activation for dual tasking and increased activation differences between dual and single task conditions during HDBR relative to pre- or post-HDBR. This HDBR-related brain activation increase for dual tasking implies that more neurocognitive control is needed for dual task execution during HDBR compared to pre- and post-HDBR. We observed a positive correlation between pre-to-post HDBR changes in dual-task cost of reaction time and pre-to-post HDBR change in dual-task cost of brain activation in several cerebral and cerebellar regions. These findings could be predictive of changes in dual task processing during spaceflight. PMID:27601982

  20. Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients

    PubMed Central

    Lim, Manyoel; Kim, June Sic; Kim, Dajung J.; Chung, Chun Kee

    2016-01-01

    Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography (MEG) activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control (HC) subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC) and orbitofrontal cortex (OFC). Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory (S2) cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM. PMID:27014041

  1. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects

    PubMed Central

    Johannesson, Elisabet; Ringström, Gisela; Abrahamsson, Hasse; Sadik, Riadh

    2015-01-01

    AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms. PMID:25593485

  2. Increased Cloud Activation Potential of Secondary Organic Aerosol for Atmospheric Mass Loadings

    SciTech Connect

    King, Stephanie M.; Rosenoern, Thomas; Shilling, John E.; Chen, Qi; Martin, Scot T.

    2009-05-01

    The effect of organic particle mass loading from 1 to ≥100 μg m-3 on the cloud condensation nuclei (CCN) properties of mixed organic-sulfate particles was investigated in the Harvard Environmental Chamber. Mixed particles were produced by the condensation of organic molecules onto ammonium sulfate particles during the dark ozonolysis of α-pinene. A continuous-flow mode of the chamber provided stable conditions over long time periods, allowing for signal integration and hence increased measurement precision at low organic mass loadings representative of atmospheric conditions. CCN activity was measured at eight mass loadings for 80- and 100-nm particles grown on 50-nm sulfate seeds. A two-component (organic/sulfate) Köhler model, which included the particle heterogeneity arising from DMA size selection and from organic volume fraction for the selected 80- and 100-nm particles, was used to predict CCN activity. For organic mass loadings of 2.9 μg m-3 and greater, the observed activation curves were well predicted using a single set of physicochemical parameters for the organic component. For mass loadings of 1.74 μg m-3 and less, the observed CCN activity increased beyond predicted values using the same parameters, implying changed physicochemical properties of the organic component. Of possible changes in surface tension, effective molecular weight, and effective density, a sensitivity analysis implicated a decrease of up to 10% in surface tension at low mass loadings as the plausible dominant mechanism for the observed increase in CCN activity.

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

    PubMed

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

    2013-08-01

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

  4. [A workplace intervention aimed at increasing awareness in nursing personnel performing manual handling activities].

    PubMed

    Scorpiniti, A; Lorusso, A; L'Abbate, N

    2007-01-01

    Here we describe a workplace intervention aimed at reducing the risk of low back pain in nursing personnel. The intervention we carried out included a specific ergonomic training and an exercise program according to the Feldenkrais Method. After the intervention, we evaluated its effect on the execution of manual handling activities in nurses. We found an increased rate of correct manual handling in the post-intervention period. PMID:18410001

  5. Increasing Supercycle Lengths of Active SU UMa-type Dwarf Novae

    NASA Astrophysics Data System (ADS)

    Otulakowska-Hypka, M.; Olech, A.

    2014-12-01

    We present observational evidence that supercycle lengths of the most active SU UMa-type stars are increasing during the past decades. We analyzed a large number of photometric measurements from available archives and found that this effect is generic for this class of stars, independently of their evolutionary status. This finding is in agreement with previous predictions and the most recent work of Patterson et al. (2012) on BK Lyn.

  6. Increase in Operator's Sympathetic Nerve Activity during Complicated Hepatobiliary Surgery: Evidence for Surgeons' Mental Stress.

    PubMed

    Yamanouchi, Kosho; Hayashida, Naomi; Kuba, Sayaka; Sakimura, Chika; Kuroki, Tamotsu; Togo, Michita; Katayama, Noritada; Takamura, Noboru; Eguchi, Susumu

    2015-01-01

    Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p < 0.01) and these did not return to the baseline level one hour after the operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p < 0.01) during the operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances. PMID:26466520

  7. Mitochondrial permeabilization without caspase activation mediates the increase of basal apoptosis in cells lacking Nrf2.

    PubMed

    Ariza, Julia; González-Reyes, José A; Jódar, Laura; Díaz-Ruiz, Alberto; de Cabo, Rafael; Villalba, José Manuel

    2016-06-01

    Nuclear factor E2-related factor-2 (Nrf2) is a cap'n'collar/basic leucine zipper (b-ZIP) transcription factor which acts as sensor of oxidative and electrophilic stress. Low levels of Nrf2 predispose cells to chemical carcinogenesis but a dark side of Nrf2 function also exists because its unrestrained activation may allow the survival of potentially dangerous damaged cells. Since Nrf2 inhibition may be of therapeutic interest in cancer, and a decrease of Nrf2 activity may be related with degenerative changes associated with aging, it is important to investigate how the lack of Nrf2 function activates molecular mechanisms mediating cell death. Murine Embryonic Fibroblasts (MEFs) bearing a Nrf2 deletion (Nrf2KO) displayed diminished cellular growth rate and shortened lifespan compared with wild-type MEFs. Basal rates of DNA fragmentation and histone H2A.X phosphorylation were higher in Nrf2KO MEFs, although steady-state levels of reactive oxygen species were not significantly increased. Enhanced rates of apoptotic DNA fragmentation were confirmed in liver and lung tissues from Nrf2KO mice. Apoptosis in Nrf2KO MEFs was associated with a decrease of Bcl-2 but not Bax levels, and with the release of the mitochondrial pro-apoptotic factors cytochrome c and AIF. Procaspase-9 and Apaf-1 were also increased in Nrf2KO MEFs but caspase-3 was not activated. Inhibition of XIAP increased death in Nrf2KO but not in wild-type MEFs. Mitochondrial ultrastructure was also altered in Nrf2KO MEFs. Our results support that Nrf2 deletion produces mitochondrial dysfunction associated with mitochondrial permeabilization, increasing basal apoptosis through a caspase-independent and AIF-dependent pathway. PMID:27016073

  8. Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus.

    PubMed

    Boschen, K E; Ruggiero, M J; Klintsova, A Y

    2016-06-01

    Aberrant activation of the developing immune system can have long-term negative consequences on cognition and behavior. Teratogens, such as alcohol, activate microglia, the brain's resident immune cells, which could contribute to the lifelong deficits in learning and memory observed in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. The current study investigates the microglial response of the brain 24h following neonatal alcohol exposure (postnatal days (PDs) 4-9, 5.25g/kg/day). On PD10, microglial cell counts and area of cell territory were assessed using unbiased stereology in the hippocampal subfields CA1, CA3 and dentate gyrus (DG), and hippocampal expression of pro- and anti-inflammatory genes was analyzed. A significant decrease in microglial cell counts in CA1 and DG was found in alcohol-exposed and sham-intubated (SI) animals compared to undisturbed suckle controls (SCs), suggesting overlapping effects of alcohol exposure and intubation alone on the neuroimmune response. Cell territory was decreased in alcohol-exposed animals in CA1, CA3, and DG compared to controls, suggesting the microglia have shifted to a more activated state following alcohol treatment. Furthermore, both alcohol-exposed and SI animals had increased levels of pro-inflammatory cytokines IL-1β, TNF-α, CD11b, and CCL4; in addition, CCL4 was significantly increased in alcohol-exposed animals compared to SI as well. Alcohol-exposed animals also showed increased levels of anti-inflammatory cytokine TGF-β compared to both SI and SCs. In summary, the number and activation of microglia in the neonatal hippocampus are both affected in a rat model of FASD, along with increased gene expression of pro- and anti-inflammatory cytokines. This study shows that alcohol exposure during development induces a neuroimmune response, potentially contributing to long-term alcohol-related changes to cognition, behavior and immune function. PMID:26996510

  9. Improved oxygen reduction activity on Pt3Ni(111) via increased surface site availability.

    PubMed

    Stamenkovic, Vojislav R; Fowler, Ben; Mun, Bongjin Simon; Wang, Guofeng; Ross, Philip N; Lucas, Christopher A; Marković, Nenad M

    2007-01-26

    The slow rate of the oxygen reduction reaction (ORR) in the polymer electrolyte membrane fuel cell (PEMFC) is the main limitation for automotive applications. We demonstrated that the Pt3Ni(111) surface is 10-fold more active for the ORR than the corresponding Pt(111) surface and 90-fold more active than the current state-of-the-art Pt/C catalysts for PEMFC. The Pt3Ni(111) surface has an unusual electronic structure (d-band center position) and arrangement of surface atoms in the near-surface region. Under operating conditions relevant to fuel cells, its near-surface layer exhibits a highly structured compositional oscillation in the outermost and third layers, which are Pt-rich, and in the second atomic layer, which is Ni-rich. The weak interaction between the Pt surface atoms and nonreactive oxygenated species increases the number of active sites for O2 adsorption. PMID:17218494

  10. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  11. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  12. Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy.

    PubMed

    Oishi, Yoshimi; Tsukamoto, Hayato; Yokokawa, Takumi; Hirotsu, Keisuke; Shimazu, Mariko; Uchida, Kenji; Tomi, Hironori; Higashida, Kazuhiko; Iwanaka, Nobumasa; Hashimoto, Takeshi

    2015-03-15

    We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals. PMID:25571987

  13. Depression Increases Sympathetic Activity and Exacerbates Myocardial Remodeling after Myocardial Infarction: Evidence from an Animal Experiment

    PubMed Central

    Liu, Tao; Yuan, Xiaoran; Ruan, Bing; Sun, Lifang; Tang, Yanhong; Yang, Bo; Hu, Dan; Huang, Congxin

    2014-01-01

    Depression is an independent risk factor for cardiovascular events and mortality in patients with myocardial infarction (MI). Excessive sympathetic activation and serious myocardial remodeling may contribute to this association. The aim of this study was to discuss the effect of depression on sympathetic activity and myocardial remodeling after MI. Wild-type (WT) rats were divided into a sham group (Sham), a myocardial infarction group (MI), a depression group (D), and a myocardial infarction plus depression group (MI+D). Compared with controls, the MI+D animals displayed depression-like behaviors and attenuated body weight gain. The evaluation of sympathetic activity showed an increased level in plasma concentrations of epinephrine and norepinephrine and higher expression of myocardial tyrosine hydroxylase in the MI+D group than the control groups (p<0.05 for all). Cardiac function and morphologic analyses revealed a decreased fractional shortening accompanied by increased left ventricular dimensions, thinning myocardium wall, and reduced collagen repair in the MI+D group compared with the MI group (p<0.05 for all). Frequent premature ventricular contractions, prolonged QT duration and ventricular repolarization duration, shorted effective refractory period, and increased susceptibility to ventricular arrhythmia were displayed in MI+D rats. These results indicate that sympathetic hyperactivation and exacerbated myocardial remodeling may be a plausible mechanism linking depression to an adverse prognosis after MI. PMID:25036781

  14. Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control

    PubMed Central

    Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G.

    2015-01-01

    Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2–4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input–output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. PMID:24610117

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

    PubMed

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

    2014-06-01

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

  16. Improvement of aromatic thiol release through the selection of yeasts with increased β-lyase activity.

    PubMed

    Belda, Ignacio; Ruiz, Javier; Navascués, Eva; Marquina, Domingo; Santos, Antonio

    2016-05-16

    The development of a selective medium for the rapid differentiation of yeast species with increased aromatic thiol release activity has been achieved. The selective medium was based on the addition of S-methyl-l-cysteine (SMC) as β-lyase substrate. In this study, a panel of 245 strains of Saccharomyces cerevisiae strains was tested for their ability to grow on YCB-SMC medium. Yeast strains with an increased β-lyase activity grew rapidly because of their ability to release ammonium from SMC in comparison to others, and allowed for the easy isolation and differentiation of yeasts with promising properties in oenology, or another field, for aromatic thiol release. The selective medium was also helpful for the discrimination between those S. cerevisiae strains, which present a common 38-bp deletion in the IRC7 sequence (present in around 88% of the wild strains tested and are likely to be less functional for 4-mercapto-4-methylpentan-2-one (4MMP) production), and those S. cerevisiae strains homozygous for the full-length IRC7 allele. The medium was also helpful for the selection of non-Saccharomyces yeasts with increased β-lyase activity. Based on the same medium, a highly sensitive, reproducible and non-expensive GC-MS method for the evaluation of the potential volatile thiol release by different yeast isolates was developed. PMID:26971012

  17. The wheat MAP kinase phosphatase 1 alleviates salt stress and increases antioxidant activities in Arabidopsis.

    PubMed

    Zaidi, Ikram; Ebel, Chantal; Belgaroui, Nibras; Ghorbel, Mouna; Amara, Imène; Hanin, Moez

    2016-04-01

    Mitogen-activated protein kinase phosphatases (MKPs) are important negative regulators in the MAPK signaling pathways, which play crucial roles in plant growth, development and stress responses. We have previously shown that the heterologous expression of a durum wheat MKP, TMKP1, results in increased tolerance to salt stress in yeast but its particular contribution in salt stress tolerance in plants was not investigated. Here, TMKP1 was overexpressed in Arabidopsis thaliana and physiological changes were assessed in transgenic plants exposed to stress conditions. Under salt stress and especially LiCl, the TMKP1 overexpressors displayed higher germination rates in comparison to wild type plants. The enhancement of salt stress tolerance was accompanied by increased antioxidant enzyme activities, namely superoxide dismutase, catalase and peroxydases. Such increases in antioxidant activities were concomitant with lower malondialdehyde, superoxide anion O2(-) and hydrogen peroxide levels in the TMKP1 transgenic seedlings. Moreover, we provide evidence that, in contrast to the Arabidopsis ortholog AtMKP1, TMKP1 acts as a positive regulator of salt stress tolerance via its ectopic expression in the Arabidopsis mkp1 mutant. PMID:26927025

  18. The Case for Increased Physical Activity in Chronic Inflammatory Bowel Disease: A Brief Review.

    PubMed

    Shephard, R J

    2016-06-01

    Regular physical activity reduces the risk of colon cancer, but there is little information on the merits of such activity in the prevention and management of chronic inflammatory bowel disease (CIBD). The present systematic review thus documents current levels of habitual physical activity and aerobic and muscular function in CIBD, and examines the safety, practicality and efficacy of exercise programmes in countering the disease process, correcting functional deficits and enhancing quality of life. A systematic search of the Ovid/Medline database from January 1996 to May 2015 linked the terms physical activity/motor activity/physical fitness/physical training/physical education/training/exercise/exercise therapy with Crohn's disease/colitis/ulcerative colitis/inflammatory bowel disease, supplementing this information by a scanning of reference lists and personal files.12 of 16 published studies show a low level of habitual physical activity in CIBD, with sub-normal values for aerobic power, lean tissue mass and muscular strength. 3 of 4 studies suggest physical activity may reduce the risk of developing IBD, and 11 interventions all note that exercise programmes are well tolerated with some decreases of disease activity, and functional gains leading to an increased health-related quality of life. Moreover, programme compliance rates compare favourably with those seen in the treatment of other chronic conditions. More information on mechanisms is needed, but regular moderate aerobic and/or resistance exercise improves the health status of patients with CIBD both by modulating immune function and by improving physical function. A regular exercise programme should thus become an important component in the management of CIBD. PMID:27116344

  19. Increase in Mechanical Resistance to Force in a Shear-Activated Protein

    NASA Astrophysics Data System (ADS)

    Botello, Eric; Harris, Nolan; Choi, Huiwan; Zhou, Zhou; Bergeron, Angela; Dong, Jing-Fei; Kiang, Ching-Hwa

    2009-03-01

    von Willebrand factor (VWF) is the largest multimeric adhesion ligand found in human blood. Plasma VWF (pVWF) must be exposed to shear stress, like at sites of vascular injury, to be activated to bind platelets to induce blood clotting. In addition, adhesion activity of VWF is related to its polymer size, with the ultra-large form of VWF (ULVWF) being hyper-active, and forming fibers even without exposure to shear stress. We used the AFM to stretch pVWF, sheared VWF (sVWF) and ULVWF, and monitor the forces as a function of molecular extension. We showed a similar increase in force resistance to unfolding for sVWF and ULVWF when compared to pVWF. The increase in force is reduced when other molecules that are known to disrupt their fibril formation are present. Our results provide evidence that the common higher order structure of sVWF and ULVWF may affect the domain structure that causes difference in their adhesion activity compared to pVWF.

  20. Microbial diversity and activity are increased by compost amendment of metal-contaminated soil.

    PubMed

    Farrell, Mark; Griffith, Gareth W; Hobbs, Phil J; Perkins, William T; Jones, Davey L

    2010-01-01

    Unlike organic pollutants, heavy metals cannot be degraded and can constitute a persistent environmental hazard. Here, we investigated the success of different remediation strategies in promoting microbial diversity and function with depth in an acidic soil heavily contaminated with Cu, Pb and Zn. Remediation involved the incorporation of either a high- or a low-quality compost or inorganic fertilizer into the topsoil and monitoring of microbial activity and diversity with soil depth over a 4-month period. While changes in topsoil microbial activity were expected, the possible effects on the subsurface microbial community due to the downward movement of metals, nutrients and/or soluble organic matter have not been examined previously. The results showed that both compost additions, especially the low-quality compost, resulted in significantly increased bacterial and fungal diversity (as assessed by terminal restriction fragment length polymorphism) and activity compared with the inorganic and control treatments in the topsoil. Although phospholipid fatty acid profiling indicated that compost addition had promoted enhanced microbial diversity in the subsoil, no concomitant increase in subsoil microbial activity was observed, suggesting that amelioration of the heavy metals remained localized in the topsoil. We conclude that although composts can successfully immobilize heavy metals and promote ecosystem diversity/function, surface incorporation had little remedial effect below the surface layer over the course of our short-term trial. PMID:19845764

  1. Phosphorylation of a C-terminal auto-inhibitory domain increases SMARCAL1 activity.

    PubMed

    Carroll, Clinton; Bansbach, Carol E; Zhao, Runxiang; Jung, Sung Yun; Qin, Jun; Cortez, David

    2014-01-01

    SMARCAL1 promotes the repair and restart of damaged replication forks. Either overexpression or silencing SMARCAL1 causes the accumulation of replication-associated DNA damage. SMARCAL1 is heavily phosphorylated. Here we identify multiple phosphorylation sites, including S889, which is phosphorylated even in undamaged cells. S889 is highly conserved through evolution and it regulates SMARCAL1 activity. Specifically, S889 phosphorylation increases the DNA-stimulated ATPase activity of SMARCAL1 and increases its ability to catalyze replication fork regression. A phosphomimetic S889 mutant is also hyperactive when expressed in cells, while a non-phosphorylatable mutant is less active. S889 lies within a C-terminal region of the SMARCAL1 protein. Deletion of the C-terminal region also creates a hyperactive SMARCAL1 protein suggesting that S889 phosphorylation relieves an auto-inhibitory function of this SMARCAL1 domain. Thus, S889 phosphorylation is one mechanism by which SMARCAL1 activity is regulated to ensure the proper level of fork remodeling needed to maintain genome integrity during DNA synthesis. PMID:24150942

  2. G-1-activated membrane estrogen receptors mediate increased contractility of the human myometrium.

    PubMed

    Maiti, K; Paul, J W; Read, M; Chan, E C; Riley, S C; Nahar, P; Smith, R

    2011-06-01

    Estrogens are key mediators of increased uterine contractility at labor. We sought to determine whether membrane-associated estrogen receptors, such as the recently described seven-transmembrane receptor G protein-coupled receptor 30 (GPR30), mediated some of this effect. Using human myometrium obtained at term cesarean section before or after the onset of labor, we demonstrated the presence of GPR30 mRNA and protein using quantitative RT-PCR and Western blotting. GPR30 receptor was localized to the cell membrane and often colocalized with calveolin-1. Using the specific estrogen membrane receptor agonist G-1 and myometrial explants, we showed that membrane receptor activation led to phosphorylation of MAPK and the actin-modifying small heat shock protein 27. Using myometrial strips incubated with G-1 or vehicle we demonstrated that estrogen membrane receptor activation increased the myometrial contractile response to oxytocin. These data suggest that activation of the plasma membrane estrogen receptor GPR30 likely participates in the physiology of the human myometrium during pregnancy and identifies it as a potential target to modify uterine activity. PMID:21427217

  3. Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

    PubMed Central

    Wong, Carmen P.; Rinaldi, Nicole A.; Ho, Emily

    2015-01-01

    Scope Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. Methods and results An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency up-regulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, that coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. Conclusion Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation. PMID:25656040

  4. Increased atypical PKC expression and activity in the phrenic motor nucleus following cervical spinal injury

    PubMed Central

    Guenther, C.H.; Windelborn, J.A.; Tubon, T.C.; Yin, J.C.P.; Mitchell, G.S.

    2012-01-01

    Atypical protein kinase C (aPKC) isoforms are expressed in phrenic motor neurons, a group of motor neurons critical for breathing. Following C2 cervical hemisection (C2HS), spontaneous plasticity occurs in crossed-spinal synaptic pathways to phrenic motor neurons, at least partially restoring inspiratory phrenic activity below the injury. Since aPKCs are necessary for synaptic plasticity in other systems, we tested the hypothesis that C2HS increases aPKC expression and activity in spinal regions associated with the phrenic motor nucleus. C2 laminectomy (sham) or C2HS was performed on adult, male Lewis rats. Ventral spinal segments C3–5 were harvested 1, 3 or 28 days post-surgery, and prepared for aPKC enzyme activity assays and immunoblots. Ventral cervical aPKC activity was elevated 1 and 28, but not 3, days post-C2HS (1 day: 63% vs sham ipsilateral to injury; p<0.05; 28 day: 426% vs sham; p<0.05; no difference in ipsilateral vs contralateral response). Total PKCζ/ι protein expression was unchanged by C2HS, but total and phosphorylated PKMζ (constitutively active PKCζ isoform) increased ipsilateral to injury 28 days post-C2HS (p<0.05). Ipsilateral aPKC activity and expression were strongly correlated (r2=0.675, p<0.001). In a distinct group of rats, immunohistochemistry confirmed that aPKCs are expressed in neurons 28 days post-C2HS, including large, presumptive phrenic motor neurons; aPKCs were not detected in adjacent microglia (OX-42 positive cells) or astrocytes (GFAP positive cells). Changes in aPKC expression in the phrenic motor nucleus following C2HS suggests that aPKCs may contribute to functional recovery following cervical spinal injury. PMID:22329943

  5. Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running

    NASA Technical Reports Server (NTRS)

    Fluck, M.; Waxham, M. N.; Hamilton, M. T.; Booth, F. W.

    2000-01-01

    Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca(2+)/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca(2+), we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca(2+)-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca(2+)/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca(2+)-independent and Ca(2+)/CaM-dependent forms of Ca(2+)/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca(2+)-independent form of CaMKII was increased, like the Ca(2+)-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca(2+)-independent SRF kinase was increased, no alteration occurred in Ca(2+)/CaM-dependent SRF kinase activity. Thus any role of Ca(2+)-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.

  6. Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis

    PubMed Central

    Mebarek, Saïda; Ermak, Natalia; Benzaria, Amal; Vicca, Stéphanie; Dubois, Madeleine; Némoz, Georges; Laville, Martine; Lacour, Bernard; Véricel, Evelyne; Lagarde, Michel; Prigent, Annie-France

    2009-01-01

    Dietary intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However most human studies examined the combined effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate (TPA) plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL (oxLDL). Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600mg) in a triacylglycerol form containing DHA as the only PUFA, for two weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400mg DHA/day. The TPA plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400mg DHA/day, with a maximum after 800mg intake, and was positively correlated (P<0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxLDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. OxLDL apoptotic effect was significantly attenuated after 400mg DHA/day and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxLDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis. PMID:18710607

  7. Increased oxidation-related glutathionylation and carbonic anhydrase activity in endometriosis.

    PubMed

    Andrisani, Alessandra; Donà, Gabriella; Brunati, Anna Maria; Clari, Giulio; Armanini, Decio; Ragazzi, Eugenio; Ambrosini, Guido; Bordin, Luciana

    2014-06-01

    This study examined the possible involvement of carbonic anhydrase activation in response to an endometriosis-related increase in oxidative stress. Peripheral blood samples obtained from 27 healthy controls and 30 endometriosis patients, classified as having endometriosis by histological examination of surgical specimens, were analysed by multiple immunoassay and carbonic anhydrase activity assay. Red blood cells (RBC) were analysed for glutathionylated protein (GSSP) content in the membrane, total glutathione (GSH) in the cytosol and carbonic anhydrase concentration and activity. In association with a membrane increase of GSSP and a cytosolic decrease of GSH content in endometriosis patients, carbonic anhydrase significantly increased (P < 0.0001) both monomerization and activity compared with controls. This oxidation-induced activation of carbonic anhydrase was positively and significantly correlated with the GSH content of RBC (r = 0.9735, P < 0.001) and with the amount of the 30-kDa monomer of carbonic anhydrase (r = 0.9750, P < 0.001). Because carbonic anhydrase activation is implied in many physiological and biochemical processes linked to pathologies such as glaucoma, hypertension, obesity and infections, carbonic anhydrase activity should be closely monitored in endometriosis. These data open promising working perspectives for diagnosis and treatment of endometriosis and hopefully of other oxidative stress-related diseases. Endometriosis is a chronic disease associated with infertility and local inflammatory response, which is thought to spread rapidly throughout the body as a systemic subclinical inflammation. One of the causes in the pathogenesis/evolution of endometriosis is oxidative stress, which occurs when reactive oxygen species are produced faster than the endogenous antioxidant defence systems can neutralize them. Once produced, reactive oxygen species can alter the morphological and functional properties of endothelial cells, including

  8. Increased Neural Activation during Picture Encoding and Retrieval in 60-Year-Olds Compared to 20-Year-Olds

    ERIC Educational Resources Information Center

    Burgmans, S.; van Boxtel, M. P. J.; Vuurman, E. F. P. M.; Evers, E. A. T.; Jolles, J.

    2010-01-01

    Brain aging has been associated with both reduced and increased neural activity during task execution. The purpose of the present study was to investigate whether increased neural activation during memory encoding and retrieval is already present at the age of 60 as well as to obtain more insight into the mechanism behind increased activity.…

  9. l-Tyrosine-loaded nanoparticles increase the antitumoral activity of direct electric current in a metastatic melanoma cell model

    PubMed Central

    de Campos, Vânia Emerich Bucco; Teixeira, Cesar Augusto Antunes; da Veiga, Venicio Feo; Júnior, Eduardo Ricci; Holandino, Carla

    2010-01-01

    Inhibition of tumor growth induced by treatment with direct electric current (DC) has been reported in several models. One of the mechanisms responsible for the antitumoral activity of DC is the generation of oxidative species, known as chloramines. With the aim of increasing chloramine production in the electrolytic medium and optimizing the antitumoral effects of DC, poly(ɛ-caprolactone) (PCL) nanoparticles (NPs) loaded with the amino acid tyrosine were obtained. The physical–chemical characterization showed that the NPs presented size in nanometric range and monomodal distribution. A slightly negative electrokinetic potential was also found in both blank NPs and l-tyrosine-loaded PCL NPs. The yield of the loading process was approximately 50%. Within 3 h of dissolution assay, a burst release of about 80% l-tyrosine was obtained. The in vitro cytotoxicity of DC was significantly increased when associated with l-tyrosine-loaded NPs, using a murine multidrug-resistant melanoma cell line model. This study showed that the use of the combination of nanotechnology and DC has a promising antineoplastic potential and opens a new perspective in cancer therapy. PMID:21187948

  10. Increased Error-Related Brain Activity Distinguishes Generalized Anxiety Disorder With and Without Comorbid Major Depressive Disorder

    PubMed Central

    Weinberg, Anna; Klein, Daniel N.; Hajcak, Greg

    2013-01-01

    Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are so frequently comorbid that some have suggested that the 2 should be collapsed into a single overarching “distress” disorder. Yet there is also increasing evidence that the 2 categories are not redundant. Neurobehavioral markers that differentiate GAD and MDD would be helpful in ongoing efforts to refine classification schemes based on neurobiological measures. The error-related negativity (ERN) may be one such marker. The ERN is an event-related potential component presenting as a negative deflection approximately 50 ms following an erroneous response and reflects activity of the anterior cingulate cortex. There is evidence for an enhanced ERN in individuals with GAD, but the literature in MDD is mixed. The present study measured the ERN in 26 GAD, 23 comorbid GAD and MDD, and 36 control participants, all of whom were female and medication-free. Consistent with previous research, the GAD group was characterized by a larger ERN and an increased difference between error and correct trials than controls. No such enhancement was evident in the comorbid group, suggesting comorbid depression may moderate the relationship between the ERN and anxiety. The present study further suggests that the ERN is a potentially useful neurobiological marker for future studies that consider the pathophysiology of multiple disorders in order to construct or refine neurobiologically based diagnostic phenotypes. PMID:22564180

  11. Who will increase their physical activity? Predictors of change in objectively measured physical activity over 12 months in the ProActive cohort

    PubMed Central

    2010-01-01

    Background The aim was to identify predictors of change in objectively measured physical activity over 12 months in the ProActive cohort to improve understanding of factors influencing change in physical activity. Methods ProActive is a physical activity promotion trial that took place in Eastern England (1999-2004). 365 offspring of people with type 2 diabetes underwent measurement of physical activity energy expenditure (PAEE) using heart rate monitoring, fitness, and anthropometric and biochemical status at baseline and 1 year (n = 321). Linear regression was used to quantify the associations between baseline demographic, clinical, psychosocial and behavioural variables and change in PAEE over 12 months. This study is registered as ISRCTN61323766. Results ProActive participants significantly increased their PAEE by 0.6 kj/min (SD 4.2, p = 0.006) over one year, the equivalent of around 20 minutes brisk walking/day. Male sex and higher fitness at baseline predicted increase in PAEE. No significant associations were found for any other variables. Very few baseline demographic, clinical, psychosocial and behavioural predictors were associated with change in objectively measured physical activity. Conclusions Traditional baseline determinants of self-reported physical activity targeted by behavioural interventions may be relatively weak predictors of change in objectively measured physical activity. Further research is needed to improve our understanding of factors influencing change in physical activity to inform the development and targeting of interventions. PMID:20433700

  12. Increasing physical activity and exercise in lung cancer: reviewing safety, benefits, and application.

    PubMed

    Bade, Brett C; Thomas, D David; Scott, JoAnn B; Silvestri, Gerard A

    2015-06-01

    Lung cancer continues to be a difficult disease frequently diagnosed in late stages with a high mortality and symptom burden. In part because of frequent lung comorbidity, even lung cancer survivors often remain symptomatic and functionally limited. Though targeted therapy continues to increase treatment options for advanced-stage disease, symptom burden remains high with few therapeutic options. In the last several decades, exercise and physical activity have arisen as therapeutic options for obstructive lung disease and lung cancer. To date, exercise has been shown to reduce symptoms, increase exercise tolerance, improve quality of life, and potentially reduce length of stay and postoperative complications. Multiple small trials have been performed in perioperative non-small-cell lung cancer patients, although fewer studies are available for patients with advanced-stage disease. Despite the increased interest in this subject over the last few years, a validated exercise regimen has not been established for perioperative or advanced-stage disease. Clinicians underutilize exercise and pulmonary rehabilitation as a therapy, in part because of the lack of evidence-based consensus as to how and when to implement increasing physical activity. This review summarizes the existing evidence on exercise in lung cancer patients. PMID:25831230

  13. Melatonin receptor activation increases glutamatergic synaptic transmission in the rat medial lateral habenula.

    PubMed

    Evely, Katherine M; Hudson, Randall L; Dubocovich, Margarita L; Haj-Dahmane, Samir

    2016-05-01

    Melatonin (MLT) is secreted from the pineal gland and mediates its physiological effects through activation of two G protein-coupled receptors, MT1 and MT2 . These receptors are expressed in several brain areas, including the habenular complex, a pair of nuclei that relay information from forebrain to midbrain and modulate a plethora of behaviors, including sleep, mood, and pain. However, so far, the precise mechanisms by which MLT control the function of habenula neurons remain unknown. Using whole cell recordings from male rat brain slices, we examined the effects of MLT on the excitability of medial lateral habenula (MLHb) neurons. We found that MLT had no significant effects on the intrinsic excitability of MLHb neurons, but profoundly increased the amplitude of glutamate-mediated evoked excitatory post-synaptic currents (EPSC). The increase in strength of glutamate synapses onto MLHb neurons was mediated by an increase in glutamate release. The MLT-induced increase in glutamatergic synaptic transmission was blocked by the competitive MT1 /MT2 receptor antagonist luzindole (LUZ). These results unravel a potential cellular mechanism by which MLT receptor activation enhances the excitability of MLHb neurons. The MLT-mediated control of glutamatergic inputs to the MLHb may play a key role in the modulation of various behaviors controlled by the habenular complex. PMID:26799638

  14. Thyroid hormones increase Na -H exchange activity in renal brush border membranes

    SciTech Connect

    Kinsella, J.; Sacktor, B.

    1985-06-01

    Na -H exchange activity, i.e., amiloride-sensitive Na and H flux, in renal proximal tubule brush border (luminal) membrane vesicles was increased in the hyperthyroid rat and decreased in the hypothyroid rat, relative to the euthyroid animal. A positive correlation was found between Na -H exchange activity and serum concentrations of thyroxine (T4) and triiodothyronine (T3). The thyroid status of the animal did not alter amiloride-insensitive Na uptake. The rate of passive pH gradient dissipation was higher in membrane vesicles from hyperthyroid rats compared to the rate in vesicles from hypothyroid animals, a result which would tend to limit the increase in Na uptake in vesicles from hyperthyroid animals. Na -dependent phosphate uptake was increased in membrane vesicles from hyperthyroid rats; Na -dependent D-glucose and L-proline uptakes were not changed by the thyroid status of the animal. The effect of thyroid hormones in increasing the uptake of Na in the brush border membrane vesicle is consistent with the action of the hormones in enhancing renal Na reabsorption.

  15. Increases in plasma lutein through supplementation are correlated with increases in physical activity and reductions in sedentary time in older adults.

    PubMed

    Thomson, Rebecca L; Coates, Alison M; Howe, Peter R C; Bryan, Janet; Matsumoto, Megumi; Buckley, Jonathan D

    2014-01-01

    Cross-sectional studies have reported positive relationships between serum lutein concentrations and higher physical activity levels. The purpose of the study was to determine whether increasing plasma lutein levels increases physical activity. Forty-four older adults (BMI, 25.3 ± 2.6 kg/m²; age, 68.8 ± 6.4 year) not meeting Australian physical activity guidelines (150 min/week of moderate to vigorous activity) were randomized to consume capsules containing 21 mg of lutein or placebo with 250 mL of full-cream milk per day for 4 weeks and encouraged to increase physical activity. Physical activity was assessed by self-report, pedometry and accelerometry (daily activity counts and sedentary time). Exercise self-efficacy was assessed by questionnaire. Thirty-nine participants competed the study (Lutein = 19, Placebo = 20). Lutein increased plasma lutein concentrations compared with placebo (p < 0.001). Absolute and percentage changes in plasma lutein were inversely associated with absolute (r = -0.36, p = 0.03) and percentage changes (r = -0.39, p = 0.02) in sedentary time. Percentage change in plasma lutein was positively associated with the percentage change in average daily activity counts (r = 0.36, p = 0.03). Exercise self-efficacy did not change (p = 0.16). Lutein increased plasma lutein, which was associated with increased physical activity and reduced sedentary time in older adults. Larger trials should evaluate whether Lutein can provide health benefits over the longer term. PMID:24594505

  16. Estrogen increases ENaC activity via PKCδ signaling in renal cortical collecting duct cells.

    PubMed

    Yusef, Yamil R; Thomas, Warren; Harvey, Brian J

    2014-05-01

    The most active estrogen, 17β-estradiol (E2), has previously been shown to stimulate a female sex-specific antisecretory response in the intestine. This effect is thought to contribute to the increase in whole body extracellular fluid (ECF) volume which occurs in high estrogen states, such as in the implantation window during estrous cycle. The increased ECF volume may be short-circuited by a renal compensation unless estrogen exerts a proabsorptive effect in the nephron. Thus, the effect of E2 on ENaC in kidney cortical collecting duct (CCD) cells is of interest to understand estrogen regulation of ECF volume. Previous studies showed a rapid stimulatory effect of estrogen on ENaC in bronchial epithelium. In this study we examined if such a rapid effect on Na(+) absorption could occur in the kidney. Experiments were carried out on murine M1-CCD cell cultures. E2 (25 nmol/L) treatment caused a rapid-onset (<15 min) and sustained increase in the amiloride-sensitive Na(+) current (INa) in CCD monolayers mounted in Ussing chambers (control, 1.9 ± 0.2 μA/cm(2); E2, 4.7 ± 0.3 μA/cm(2); n = 43, P < 0.001), without affecting the ouabain-sensitive Na(+)/K(+) pump current. The INa response to E2 was inhibited by PKCδ activity antagonism with rottlerin (5 μmol/L), inhibition of matrix metalloproteinases activity with GM6001 (1 μmol/L), inhibition of EGFR activity with AG1478 (10 μmol/L), inhibition of PLC activity with U-73122 (10 μmol/L), and inhibition of estrogen receptors with the general ER antagonist ICI-182780 (100 nmol/L). The estrogen activation of INa could be mimicked by the ERα agonist PPT (1 nmol/L). The nuclear excluded estrogen dendrimer conjugate (EDC) induced similar stimulatory effects on INa comparable to free E2. The end target for E2 stimulation of PKCδ was shown to be an increased abundance of the γ-ENaC subunit in the apical plasma membrane of CCD cells. We have demonstrated a novel rapid "nongenomic" function of estrogen to stimulate ENa

  17. Estrogen increases ENaC activity via PKCδ signaling in renal cortical collecting duct cells

    PubMed Central

    Yusef, Yamil R.; Thomas, Warren; Harvey, Brian J.

    2014-01-01

    Abstract The most active estrogen, 17β‐estradiol (E2), has previously been shown to stimulate a female sex‐specific antisecretory response in the intestine. This effect is thought to contribute to the increase in whole body extracellular fluid (ECF) volume which occurs in high estrogen states, such as in the implantation window during estrous cycle. The increased ECF volume may be short‐circuited by a renal compensation unless estrogen exerts a proabsorptive effect in the nephron. Thus, the effect of E2 on ENaC in kidney cortical collecting duct (CCD) cells is of interest to understand estrogen regulation of ECF volume. Previous studies showed a rapid stimulatory effect of estrogen on ENaC in bronchial epithelium. In this study we examined if such a rapid effect on Na+ absorption could occur in the kidney. Experiments were carried out on murine M1‐CCD cell cultures. E2 (25 nmol/L) treatment caused a rapid‐onset (<15 min) and sustained increase in the amiloride‐sensitive Na+ current (INa) in CCD monolayers mounted in Ussing chambers (control, 1.9 ± 0.2 μA/cm2; E2, 4.7 ± 0.3 μA/cm2; n = 43, P < 0.001), without affecting the ouabain‐sensitive Na+/K+ pump current. The INa response to E2 was inhibited by PKCδ activity antagonism with rottlerin (5 μmol/L), inhibition of matrix metalloproteinases activity with GM6001 (1 μmol/L), inhibition of EGFR activity with AG1478 (10 μmol/L), inhibition of PLC activity with U‐73122 (10 μmol/L), and inhibition of estrogen receptors with the general ER antagonist ICI‐182780 (100 nmol/L). The estrogen activation of INa could be mimicked by the ERα agonist PPT (1 nmol/L). The nuclear excluded estrogen dendrimer conjugate (EDC) induced similar stimulatory effects on INa comparable to free E2. The end target for E2 stimulation of PKCδ was shown to be an increased abundance of the γ‐ENaC subunit in the apical plasma membrane of CCD cells. We have demonstrated a novel rapid “nongenomic” function of

  18. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    PubMed

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes. PMID:18814656

  19. Dengue Virus NS1 Protein Modulates Cellular Energy Metabolism by Increasing Glyceraldehyde-3-Phosphate Dehydrogenase Activity

    PubMed Central

    Allonso, Diego; Andrade, Iamara S.; Conde, Jonas N.; Coelho, Diego R.; Rocha, Daniele C. P.; da Silva, Manuela L.; Ventura, Gustavo T.

    2015-01-01

    ABSTRACT Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46- to 55-kDa glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH in vitro. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV. IMPORTANCE Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV). Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the

  20. Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn

    PubMed Central

    Storchi, Riccardo; Milosavljevic, Nina; Eleftheriou, Cyril G.; Martial, Franck P.; Orlowska-Feuer, Patrycja; Bedford, Robert A.; Brown, Timothy M.; Montemurro, Marcelo A.; Petersen, Rasmus S.; Lucas, Robert J.

    2015-01-01

    Twice a day, at dawn and dusk, we experience gradual but very high amplitude changes in background light intensity (irradiance). Although we perceive the associated change in environmental brightness, the representation of such very slow alterations in irradiance by the early visual system has been little studied. Here, we addressed this deficit by recording electrophysiological activity in the mouse dorsal lateral geniculate nucleus under exposure to a simulated dawn. As irradiance increased we found a widespread enhancement in baseline firing that extended to units with ON as well as OFF responses to fast luminance increments. This change in baseline firing was equally apparent when the slow irradiance ramp appeared alone or when a variety of higher-frequency artificial or natural visual stimuli were superimposed upon it. Using a combination of conventional knockout, chemogenetic, and receptor-silent substitution manipulations, we continued to show that, over higher irradiances, this increase in firing originates with inner-retinal melanopsin photoreception. At the single-unit level, irradiance-dependent increases in baseline firing were strongly correlated with improvements in the amplitude of responses to higher-frequency visual stimuli. This in turn results in an up to threefold increase in single-trial reliability of fast visual responses. In this way, our data indicate that melanopsin drives a generalized increase in dorsal lateral geniculate nucleus excitability as dawn progresses that both conveys information about changing background light intensity and increases the signal:noise for fast visual responses. PMID:26438865

  1. Downscaling CMIP5 climate models shows increased tropical cyclone activity over the 21st century

    PubMed Central

    Emanuel, Kerry A.

    2013-01-01

    A recently developed technique for simulating large [O(104)] numbers of tropical cyclones in climate states described by global gridded data is applied to simulations of historical and future climate states simulated by six Coupled Model Intercomparison Project 5 (CMIP5) global climate models. Tropical cyclones downscaled from the climate of the period 1950–2005 are compared with those of the 21st century in simulations that stipulate that the radiative forcing from greenhouse gases increases by over preindustrial values. In contrast to storms that appear explicitly in most global models, the frequency of downscaled tropical cyclones increases during the 21st century in most locations. The intensity of such storms, as measured by their maximum wind speeds, also increases, in agreement with previous results. Increases in tropical cyclone activity are most prominent in the western North Pacific, but are evident in other regions except for the southwestern Pacific. The increased frequency of events is consistent with increases in a genesis potential index based on monthly mean global model output. These results are compared and contrasted with other inferences concerning the effect of global warming on tropical cyclones. PMID:23836646

  2. Downscaling CMIP5 climate models shows increased tropical cyclone activity over the 21st century.

    PubMed

    Emanuel, Kerry A

    2013-07-23

    A recently developed technique for simulating large [O(10(4))] numbers of tropical cyclones in climate states described by global gridded data is applied to simulations of historical and future climate states simulated by six Coupled Model Intercomparison Project 5 (CMIP5) global climate models. Tropical cyclones downscaled from the climate of the period 1950-2005 are compared with those of the 21st century in simulations that stipulate that the radiative forcing from greenhouse gases increases by over preindustrial values. In contrast to storms that appear explicitly in most global models, the frequency of downscaled tropical cyclones increases during the 21st century in most locations. The intensity of such storms, as measured by their maximum wind speeds, also increases, in agreement with previous results. Increases in tropical cyclone activity are most prominent in the western North Pacific, but are evident in other regions except for the southwestern Pacific. The increased frequency of events is consistent with increases in a genesis potential index based on monthly mean global model output. These results are compared and contrasted with other inferences concerning the effect of global warming on tropical cyclones. PMID:23836646

  3. Increased poly(ADP-ribose)polymerase activity in cells infected by human immunodeficiency virus type-1.

    PubMed

    Furlini, G; Re, M C; La Placa, M

    1991-04-01

    Poly(ADP-ribose)polymerase is a chromatin-bound enzyme which is activated by free DNA ends and is therefore stimulated by a variety of DNA-damaging agents. The enzyme transfers the ADP moiety of NAD to nuclear proteins to create protein-bound ADP-ribose polymers. Under conditions favouring an accelerated poly(ADP-ribose) polymer formation, the enzyme may exhaust cellular NAD pools. At the same time, or shortly thereafter ATP levels drop and cell viability eventually declines. As a series of chemical and physical agents which may play a role in activating latent HIV-1 infection or favouring HIV-1 replication, have a DNA-damaging activity, we investigated the behaviour of poly(ADP-ribose)polymerase activity in various types of HIV-1-infected cells. The results obtained show that HIV-1-infected cells to possess an increased poly(ADP-ribosol)ating activity together with an accentuated fragmentation of cellular DNA which are associated with the time course of HIV-1 replication. These data give circumstantial support to the hypothesis that a NAD-depdendent cellular suicide response to DNA damage, could play a role in the death of HIV-1 infected cells. In this respect, the impared immunocompetence of HIV-1-infected patients could bear some resemblance to immune attribution that sometimes accompanies some inborn errors affecting DNA precursor metabolism and DNA integrity. PMID:1906973

  4. Using function-focused care to increase physical activity among older adults.

    PubMed

    Resnick, Barbara; Galik, Elizabeth

    2013-01-01

    Despite the known benefits of physical activity for older adults, adherence to regular physical activity recommendations is poor. Less than half of adults in this country meet physical activity recommendations with reasons for lack of adherence including such things as access, motivation, pain, fear, comorbidities, among others. To overcome these challenges, function-focused care was developed. Function-focused care is a philosophy of care that focuses on evaluating the older adult's underlying capability with regard to function and physical activity and helping him or her optimize and maintain physical function and ability and continually increase time spent in physical activity. Examples of function-focused care include such things as using verbal cues during bathing, so the older individual performs the tasks rather than the caregiver bathing the individual; walking a resident or patient to the bathroom rather than using a urinal, or taking a resident to an exercise class. There are now over 20 studies supporting the benefits of function-focused care approaches across all settings and different types of patient groups (i.e, those with mild versus moderate-to-severe cognitive impairment). The approaches for implementation of function-focused care have also been well supported and have moved beyond establishing effectiveness to considering dissemination and implementation of this approach into real world clinical settings. The process of dissemination and implementation has likewise been articulated and supported, and ongoing work needs to continue in this venue across all care settings. PMID:24894140

  5. User-Driven Control Increases Cortical Activity during Treadmill Walking: An EEG Study

    PubMed Central

    Bulea, Thomas C.; Kim, Jonghyun; Damiano, Diane L.; Stanley, Christopher J.; Park, Hyung-Soon

    2016-01-01

    Treadmills provide a safe and efficient method for gait rehabilitation but treadmill based training paradigms have not been shown to create superior results when compared with traditional physical therapy methods such as overground training. One explanation for this may be that walking at a constant, fixed speed requires little mental engagement from the user, which has been postulated as a key factor in the success of motor learning. To increase mental engagement, we developed a user-driven treadmill control scheme. In this paper we use electroencephalography (EEG) to compare cortical activity during user-driven (active) walking with activity on a normal (passive) treadmill in nine healthy subjects. We used independent component analysis (ICA) to isolate brain activity from artifactual components. We fit equivalent dipole sources to each brain component and clustered these across subjects. Our analysis revealed that relative to the passive treadmill, active walking resulted in statistically significant decreases in spectral power, i.e. desynchronization, in the anterior cingulate, sensorimotor cortices, and posterior parietal lobe of the cortex. These results indicate that user-driven treadmills more fully engage the motor cortex and therefore could facilitate better training outcomes than a traditional treadmill. PMID:25570401

  6. Protein kinase a activity is increased in rat heart during late hypodynamic phase of sepsis.

    PubMed

    Yang, S L; Hsu, C; Lue, S I; Hsu, H K; Liu, M S

    1997-07-01

    Changes in the activities of protein kinase A (PKA, or cAMP-dependent protein kinase) in rat heart during different cardiodynamic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture. Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals killed at 9 and 18 h, respectively, after cecal ligation and puncture. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Results obtained show that during early sepsis, both type I and type II PKA activities were unaffected. During late sepsis, type I PKA activities were stimulated by 66.7-97.7%, while type II PKA activities remained constant. Kinetic analysis of the data on type I PKA during late sepsis reveals that the Vmax values for ATP, cAMP, and histone were increased by 84.7, 66.7, and 97.7%, respectively; while the Km values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA is activated in rat heart during late hypodynamic phase of sepsis. Since kinase-mediated phosphorylation plays an important role in regulating myocardial function and metabolism, an activation of type I PKA during late sepsis may contribute to the development of altered myocardial function during hypodynamic phase of sepsis. PMID:9249915

  7. A Designed “Nested” Dimer of Cyanovirin-N Increases Antiviral Activity

    PubMed Central

    Woodrum, Brian W.; Maxwell, Jason; Allen, Denysia M.; Wilson, Jennifer; Krumpe, Lauren R.H.; Bobkov, Andrey A.; Hill, R. Blake; Kibler, Karen V.; O’Keefe, Barry R.; Ghirlanda, Giovanna

    2016-01-01

    Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface of enveloped viruses. In the case of HIV, antiviral activity of CV-N is postulated to require multivalent interactions with envelope protein gp120, achieved through a pseudo-repeat of sequence that adopts two near-identical glycan-binding sites, and possibly involves a 3D-domain-swapped dimeric form of CV-N. Here, we present a covalent dimer of CV-N that increases the number of active glycan-binding sites, and we characterize its ability to recognize four glycans in solution. A CV-N variant was designed in which two native repeats were separated by the “nested” covalent insertion of two additional repeats of CV-N, resulting in four possible glycan-binding sites. The resulting Nested CV-N folds into a wild-type-like structure as assessed by circular dichroism and NMR spectroscopy, and displays high thermal stability with a Tm of 59 °C, identical to WT. All four glycan-binding domains encompassed by the sequence are functional as demonstrated by isothermal titration calorimetry, which revealed two sets of binding events to dimannose with dissociation constants Kd of 25 μM and 900 μM, assigned to domains B and B’ and domains A and A’ respectively. Nested CV-N displays a slight increase in activity when compared to WT CV-N in both an anti-HIV cellular assay and a fusion assay. This construct conserves the original binding specifityies of domain A and B, thus indicating correct fold of the two CV-N repeats. Thus, rational design can be used to increase multivalency in antiviral lectins in a controlled manner. PMID:27275831

  8. A Designed "Nested" Dimer of Cyanovirin-N Increases Antiviral Activity.

    PubMed

    Woodrum, Brian W; Maxwell, Jason; Allen, Denysia M; Wilson, Jennifer; Krumpe, Lauren R H; Bobkov, Andrey A; Hill, R Blake; Kibler, Karen V; O'Keefe, Barry R; Ghirlanda, Giovanna

    2016-01-01

    Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface of enveloped viruses. In the case of HIV, antiviral activity of CV-N is postulated to require multivalent interactions with envelope protein gp120, achieved through a pseudo-repeat of sequence that adopts two near-identical glycan-binding sites, and possibly involves a 3D-domain-swapped dimeric form of CV-N. Here, we present a covalent dimer of CV-N that increases the number of active glycan-binding sites, and we characterize its ability to recognize four glycans in solution. A CV-N variant was designed in which two native repeats were separated by the "nested" covalent insertion of two additional repeats of CV-N, resulting in four possible glycan-binding sites. The resulting Nested CV-N folds into a wild-type-like structure as assessed by circular dichroism and NMR spectroscopy, and displays high thermal stability with a Tm of 59 °C, identical to WT. All four glycan-binding domains encompassed by the sequence are functional as demonstrated by isothermal titration calorimetry, which revealed two sets of binding events to dimannose with dissociation constants Kd of 25 μM and 900 μM, assigned to domains B and B' and domains A and A' respectively. Nested CV-N displays a slight increase in activity when compared to WT CV-N in both an anti-HIV cellular assay and a fusion assay. This construct conserves the original binding specifityies of domain A and B, thus indicating correct fold of the two CV-N repeats. Thus, rational design can be used to increase multivalency in antiviral lectins in a controlled manner. PMID:27275831

  9. Overwintering Periwinkle (Vinca minor L.) Exhibits Increased Photosystem I Activity 1

    PubMed Central

    Huner, N. P. A.; Krol, M.; Williams, J. P.; Maissan, E.

    1988-01-01

    The effects of natural, overwintering conditions on photosystem I and photosystem II activity were examined in isolated thylakoids of periwinkle (Vinca minor L.), an endemic, cold-tolerant, herbaceous evergreen. DCMU-Insensitive photosystem I activity (ascorbate/dichlorophenolindophenol → methylviologen) exhibited a twofold increase in light-saturated rates upon exposure to low temperature and freezing stress with no effect on the apparent quantum yield of this reaction. DCMU-Sensitive photosystem II activity (H2O → dichlorlophenolindophenol) exhibited only minor fluctuations in light-saturated rates but a 50% decrease in the apparent quantum yield of this reaction upon exposure to overwintering conditions. This was correlated with a decrease in the 77°K fluorescence emission at 694 nanometers. These functional changes occurred with no detectable changes in the relative chlorophyll contents of the chlorophyll-protein complexes or the chlorophyll-thylakoid protein. The chlorophyll a/b varied less than 10% during any single growth year. Analyses of total leaf extracts indicated that all lipid classes exhibited increased levels of linoleic and linolenic acid. Neither the trans-Δ3-hexadecenoic acid level nor the ratio of oligomeric:monomeric light harvesting of photosystem II was affected by exposure to winter stress. The content of the major chloroplast lipids monogalactosyldiacylglycerol, digalactosyldiacylglycerol, phosphatidyl-diacyl-glycerol, and sulfoquinovosyldiacylglycerol exhibited minor fluctuations, whereas phosphatidylcholine and phosphatidylethanolamine content doubled on a mole percent or chlorophyll basis. We conclude that the previously reported increase in photosystem I activity during controlled, low temperature growth is observed during exposure to natural overwintering conditions. This appears to occur with minimal changes in the structure and composition of the photosynthetic apparatus of periwinkle. PMID:16666214

  10. Balance recovery is compromised and trunk muscle activity is increased in chronic obstructive pulmonary disease.

    PubMed

    Smith, Michelle D; Chang, Angela T; Hodges, Paul W

    2016-01-01

    Increased respiration in chronic obstructive pulmonary disease (COPD) requires greater abdominal muscle activation, which may impact on contribution of the trunk to postural control. This study aimed to determine whether recovery of balance from postural perturbations and trunk muscle activity differs in people with and without COPD before and/or after exercise. Electromyography (EMG) of the obliquus internus (OI) and externus (OE) abdominis, rectus abdominis (RA), erector spinae (ES) and deltoid muscles was recorded with surface electrodes during rapid shoulder flexion and extension. Time taken to regain baseline centre of pressure velocity (vCOP) and the number of postural adjustments following arm movement was calculated from force plate data. Time to recover balance in the direction of postural disturbance (anteroposterior vCOP) was longer in COPD, particularly more severe COPD, than controls. Mediolateral vCOP (perpendicular to the perturbation) and the number of postural adjustments did not differ between groups, but people with more severe COPD were less successful at returning their mediolateral vCOP to baseline. Abdominal muscle EMG was similar between groups, but controls had greater ES EMG during arm movements. Individuals with more severe COPD had greater OE and RA EMG both before and during arm movement compared to those with less severe COPD and controls. Following exercise, OE and ES EMG increased in people with less severe COPD. This study shows that severe COPD is associated with impaired ability to recover balance and greater trunk muscle activity during postural challenges. Augmented trunk muscle activity may limit the contribution of trunk movements to balance recovery and could contribute to increased falls risk. PMID:26471324

  11. Caffeine increases sweating sensitivity via changes in sudomotor activity during physical loading.

    PubMed

    Kim, Tae-Wook; Shin, Young-Oh; Lee, Jeong-Beom; Min, Young-Ki; Yang, Hun-Mo

    2011-11-01

    We assessed the effect of caffeine on sudomotor activity and sweating sensitivity during physical loading. Both physiological responses could occur due to energy expenditure. Subjects were 13 athletically trained males (22.1 ± 3.7 years old, 174.2 ± 5.4 cm tall, and weighing 70.9 ± 4.6 kg, with maximal oxygen consumption [VO(2)max] of 53.6 ± 4.4 mL/kg/minute). The study involved a within-subject, random, crossover design. Tests were performed following the ingestion of 3 mg/kg caffeine. The physical loading involved running for 30 minutes at 60% VO(2)max (24.0 ± 0.5°C, 40 ± 3.0% relative humidity). Tympanic temperature (TYMP) was significantly higher in the caffeine-consuming group (Caffe-I) at pre-exercise (40 minutes after caffeine intake and immediately before running) (P<.05). Mean body temperature (mT(b)) was significantly higher in the Caffe-I group at pre- and post-exercise (30 min after start of running) (P<.05). Onset time of localized sweating was significantly shorter in the Caffe-I group (P<.01), but localized sweat volume and active sweat gland output (per single gland) was significantly higher in the Caffe-I group (P<.001). Activated sweat gland density was significantly increased in the Caffe-I group on the abdomen and thigh (P<.01). In conclusion, caffeine ingestion caused not only increases in TYMP and mT(b) through thermogenesis, but also an increased sweating sensitivity via changes in sudomotor activity. PMID:21883004

  12. P-selectin increases angiotensin II-induced cardiac inflammation and fibrosis via platelet activation

    PubMed Central

    LIU, GAIZHEN; LIANG, BIN; SONG, XIAOSU; BAI, RUI; QIN, WEIWEI; SUN, XU; LU, YAN; BIAN, YUNFEI; XIAO, CHUANSHI

    2016-01-01

    Platelet activation is important in hypertension-induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P-selectin recruits leukocytes to sites of inflammation, the role of P-selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet-derived P-selectin promotes hypertensive cardiac inflammation and fibrosis. P-selectin knockout (P-sel KO) mice and wild-type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross-transplanted with platelets originating from either WT or P-sel KO mice. P-selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P-sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P-sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α-smooth muscle actin and transforming growth factor β1 (TGF-β1) expression levels were decreased in the P-sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P-sel KO mice, the number of Mac-2 (galectin-3)- and TGF-β1-positive cells was increased in mice that received WT platelets compared with those that received P-sel KO platelets, and the mRNA expression levels of collagen I and TGF-β1 were also increased. The results from the present study suggest that activated platelets secrete P-selectin to promote cardiac inflammation and fibrosis in Ang II-induced hypertension. PMID:27121797

  13. P‑selectin increases angiotensin II‑induced cardiac inflammation and fibrosis via platelet activation.

    PubMed

    Liu, Gaizhen; Liang, Bin; Song, Xiaosu; Bai, Rui; Qin, Weiwei; Sun, Xu; Lu, Yan; Bian, Yunfei; Xiao, Chuanshi

    2016-06-01

    Platelet activation is important in hypertension‑induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P‑selectin recruits leukocytes to sites of inflammation, the role of P‑selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet‑derived P‑selectin promotes hypertensive cardiac inflammation and fibrosis. P‑selectin knockout (P‑sel KO) mice and wild‑type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross‑transplanted with platelets originating from either WT or P‑sel KO mice. P‑selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P‑sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P‑sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α‑smooth muscle actin and transforming growth factor β1 (TGF‑β1) expression levels were decreased in the P‑sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P‑sel KO mice, the number of Mac‑2 (galectin‑3)‑ and TGF‑β1‑positive cells was increased in mice that received WT platelets compared with those that received P‑sel KO platelets, and the mRNA expression levels of collagen I and TGF‑β1 were also increased. The results from the present study suggest that activated platelets secrete P‑selectin to promote cardiac inflammation and fibrosis in Ang II‑induced hypertension. PMID:27121797

  14. Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

    PubMed Central

    Zhang, Mingxia; Liu, Haiying; Zhang, Guoliang; Deng, Qunyi; Huang, Jian; Gao, Zhiliang; Zhou, Boping; Feng, Carl G.; Chen, Xinchun

    2014-01-01

    Background Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. Methods Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. Results C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. Conclusions C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. PMID:24647646

  15. Frequent Surfing on Social Health Networks is Associated With Increased Knowledge and Patient Health Activation

    PubMed Central

    Grosberg, Dafna; Grinvald, Haya; Reuveni, Haim

    2016-01-01

    Background The advent of the Internet has driven a technological revolution that has changed our lives. As part of this phenomenon, social networks have attained a prominent role in health care. A variety of medical services is provided over the Internet, including home monitoring, interactive communications between the patient and service providers, and social support, among others. This study emphasizes some of the practical implications of Web-based health social networks for patients and for health care systems. Objective The objective of this study was to assess how participation in a social network among individuals with a chronic condition contributed to patient activation, based on the Patient Activation Measure (PAM). Methods A prospective, cross-sectional survey with a retrospective component was conducted. Data were collected from Camoni, a Hebrew-language Web-based social health network, participants in the diabetes mellitus, pain, hypertension, and depression/anxiety forums, during November 2012 to 2013. Experienced users (enrolled at least 6 months) and newly enrolled received similar versions of the same questionnaire including sociodemographics and PAM. Results Among 686 participants, 154 of 337 experienced and 123 of 349 newly enrolled completed the questionnaire. Positive correlations (P<.05) were found between frequency and duration of site visits and patient activation, social relationships, and chronic disease knowledge. Men surfed longer than women (χ²3=10.104, P<.05). Experienced users with diabetes surfed more than those with other illnesses and had significantly higher PAM scores (mean, M=69.3, standard deviation, SD=19.1, PAM level 4; Z=−4.197, P<.001) than new users (M=62.8, SD=18.7, PAM level 3). Disease knowledge directly predicted PAM for all users (β=.26 and .21, respectively). Frequency and duration of social health network use were correlated with increased knowledge about a chronic disease. Experienced surfers had higher PAM

  16. Increased Expression of Cathelicidin by Direct Activation of Protease-Activated Receptor 2: Possible Implications on the Pathogenesis of Rosacea

    PubMed Central

    Kim, Ji Young; Kim, Yoon Jee; Lim, Beom Jin; Sohn, Hyo Jung; Shin, Dongyun

    2014-01-01

    Purpose Recent findings of increased cathelicidin protein and its proteolytic fragments in rosacea suggest a pathogenic role for cathelicidin in this disease. The relationship between cathelicidin and protease-activated receptor 2 (PAR-2) is therefore of interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosacea and to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes. Materials and Methods Samples from 40 patients with clinicopathologic diagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensities of immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations between PAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelial growth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP). Results Cathelicidin expression was significantly higher in rosacea skin tissues than in normal tissues (p<0.001), while PAR-2 expression was not significantly higher in rosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in cultured keratinocytes, compared with PAR-2 control peptide treatment. Conclusion PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidin LL-37, a mediator of innate immune responses in the skin. PMID:25323904

  17. A self-regulation-based intervention to increase physical activity in cancer patients.

    PubMed

    Ungar, Nadine; Sieverding, Monika; Weidner, Gerdi; Ulrich, Cornelia M; Wiskemann, Joachim

    2016-01-01

    The study examined whether a behavior-change intervention focusing on self-regulatory strategies and emphasizing role model support increases physical activity (PA) among insufficiently active (not meeting PA guidelines of 150 min/week) cancer patients. Ambulatory cancer patients [N = 72; 54% female; M = 56 years, SD = 12.34; most with breast or colon cancer (34, 15%)] were enrolled in the MOTIVACTION-study, a 4-week intervention (1-hr counseling, followed by weekly phone calls), with pretest (T1), posttest (T2) and a 10-week follow-up (T3). Participants were randomized to either an exercise or to a stress management intervention (active control). The exercise intervention emphasized self-regulatory strategies (e.g. action- and coping planning and self-monitoring); patients were also encouraged to contact a physically active same-sex role model as a potential exercise partner. The active control condition consisted of coping and relaxation techniques. Sixty-seven patients remained in the study and completed the SQUASH assessment of PA and a measure of perceived stress. PA was validated by Actigraph accelerometry. At T2, 46% of the patients in the exercise group and 19% of stress management patients increased their activity levels to meet PA guidelines (>150 min/week; χ(2)(1) = 5.51, p = .019). At T3, participants in the exercise intervention maintained their exercise level (46%), but also 31% of the stress management patients met the guidelines. All patients reported reductions in perceived stress. Additional analyses comparing patients in the exercise group by role model contact (63% realized contact) revealed that those who had contact with their role model were significantly more likely to adhere to the recommended guidelines (T2:50%; T3:64%) compared to those who did not have contact with a role model (T2:39%; T3:15%), suggesting the potential of mobilizing role model support to facilitate PA. In sum, cancer patients may not only benefit from an exercise

  18. Chronic activation of CB2 cannabinoid receptors in the hippocampus increases excitatory synaptic transmission

    PubMed Central

    Kim, Jimok; Li, Yong

    2015-01-01

    The roles of CB1 cannabinoid receptors in regulating neuronal activity have been extensively characterized. Although early studies show that CB1 receptors are present in the nervous system and CB2 cannabinoid receptors are in the immune system, recent evidence indicates that CB2 receptors are also expressed in the brain. Activation or blockade of CB2 receptors in vivo induces neuropsychiatric effects, but the cellular mechanisms of CB2 receptor function are unclear. The aim of this study is to determine how activation of CB2 receptors present in the hippocampus regulates synaptic function. Here, we show that when organotypic cultures of rodent hippocampal slices were treated with a CB2 receptor agonist (JWH133 or GP1a) for 7–10 days, quantal glutamate release became more frequent and spine density was increased via extracellular signal-regulated kinases. Chronic intraperitoneal injection of JWH133 into mice also increased excitatory synaptic transmission. These effects were blocked by a CB2 receptor antagonist (SR144528) or absent from hippocampal slices of CB2 receptor knock-out mice. This study reveals a novel cellular function of CB2 cannabinoid receptors in the hippocampus and provides insights into how cannabinoid receptor subtypes diversify the roles of cannabinoids in the brain. PMID:25504573

  19. Effects of lithium on behavioral reactivity: relation to increases in brain cholinergic activity.

    PubMed

    Russell, R W; Pechnick, R; Jope, R S

    1981-01-01

    Suppression of behavior accompanying increased ACh synthesis in the brain might account, at least in part, for the preferred use of lithium in antimanic therapy. Three experiments using rats as subjects were designed to test hypotheses about relationships among lithium, ACh synthesis and behavior. Experiment 1 established that hyporeactivity and greater exploratory behavior occurred in animals under LiCl treatment conditions shown to stimulate cholinergic activity in brain. Experiment 2 provided evidence of significant differences between controls and animals on the LiCl diet. Groups tested after 1 or 2 days of LiCl showed the decrease in reactivity to successive presentations of a loud auditory stimulus which characterizes the normal process of habituation. Groups tested after 5 or 10 days of liCl showed no evidence of habituation, their reactivity throughout the period of stimulation being at a level attained by the other groups when habituation reached its final asymptote. Experiment 3 established that effects of LiCl treatment were not manifested in all aspects of behavior: there was no evidence of impairment of motor activity or coordination; no analgesia; no impairment in sensory input nor in acquisition of new behaviors. The effect of the LiCl treatment was not complete inhibition but instead suppression of reactivity to environmental stimulation under conditions shown previously to increase cholinergic activity in brain. PMID:6785802

  20. Temporal aspects of increases in eye-neck activation levels during visually deficient near work.

    PubMed

    Richter, Hans O; Camilla, Lodin; Forsman, Mikael

    2012-01-01

    In an experimental study two levels of oculomotor load were induced via optical trial lenses. Trapezius muscle activity was measured with bipolar surface electromyography and normalized to a submaximal contraction. Sixty-six subjects with a median age of 36 (range 19-47, std 8) viewed a black and white Gabor grating (5 c/deg) for two 7-min periods monocularly through a 0 D lens or binocularly through -3.5 D lenses. The effect of time was separately regressed to EMG in two different subgroups of responders: a High-Oculomotor-Load (HOL) and a Low-Oculomotor-Load (LOL) group. A linear regression model was fitted on group level with exposure time on the x-axis and normalized trapezius muscle EMG (%RVE) on the y-axis. The slope coefficient was significantly positive in the -D blur condition for only the HOL subgroup of responders: 0.926 + Time(min 1-7) × 0.088 (p = 0.002, r(2)=0.865). There was no obvious sign of this activity to level off or to stabilize. These results suggest that professional information technology users that are exposed to a high level of oculomotor load, during extended times, are at an increased risk of exhibiting an increased trap.m. activity. PMID:22317234

  1. Inflammatory Eicosanoids Increase Amyloid Precursor Protein Expression via Activation of Multiple Neuronal Receptors

    PubMed Central

    Herbst-Robinson, Katie J.; Liu, Li; James, Michael; Yao, Yuemang; Xie, Sharon X.; Brunden, Kurt R.

    2015-01-01

    Senile plaques comprised of Aβ peptides are a hallmark of Alzheimer’s disease (AD) brain, as are activated glia that release inflammatory molecules, including eicosanoids. Previous studies have demonstrated that amyloid precursor protein (APP) and Aβ levels can be increased through activation of thromboxane A2-prostanoid (TP) receptors on neurons. We demonstrate that TP receptor regulation of APP expression depends on Gαq-signaling and conventional protein kinase C isoforms. Importantly, we discovered that Gαq-linked prostaglandin E2 and leukotriene D4 receptors also regulate APP expression. Prostaglandin E2 and thromboxane A2, as well as total APP levels, were found to be elevated in the brains of aged 5XFAD transgenic mice harboring Aβ plaques and activated glia, suggesting that increased APP expression resulted from eicosanoid binding to Gαq-linked neuronal receptors. Notably, inhibition of eicosanoid synthesis significantly lowered brain APP protein levels in aged 5XFAD mice. These results provide new insights into potential AD therapeutic strategies. PMID:26672557

  2. Regulation of the phenolic profile of berries can increase their antioxidant activity.

    PubMed

    Hudec, Jozef; Kochanová, Radka; Burdová, Mária; Kobida, L'ubomír; Kogan, Grigorij; Turianica, Ivan; Chlebo, Peter; Hanácková, Eva; Slamka, Pavol

    2009-03-11

    The changes of the antioxidant activities (AOA), antiradical activities (ARA), low-density lipoprotein (LDL) oxidation, and total contents of phenolics, anthocyanins, flavonols, hydroxybenzoic acids, and hydroxycinnamic acids in black currant and black chokeberry, after treatment with ornithine decarboxylase inhibitor, a polyamine inhibitor (O-phosphoethanolamine, KF), and a phenol biosynthesis stimulator (carboxymethyl chitin glucan, CCHG), were analyzed spectrophotometrically. Gallic acid, hydroxycinnamic acids, and selected flavonol contents was analyzed by RP-HPLC. Both regulators increased the AOA measured as inhibition of peroxidation (IP) in black chokeberry, 1.71-fold after treatment with KF(1) and 1.74-fold after treatment with CCHG. In black currant IP was elevated after CCHG application only in lower dose (CCHG(1) 63.36% vs control 53.23%). In black chokeberry the total phenolics content was elevated 1.49-fold after KF(1) application and 1.31-fold after CCHG(2) application. The regulators had the lower effect on the phenolic accumulation in black currant. There was a strong relationship between the total phenolics in the both crops and anthocyanins, hydroxybenzoic acids, and hydroxycinnamic acids contents, respectively. Both regulators significantly changed the ratio of conjugated (rutin) to free (quercetin) flavonol mainly in black chokeberry. The antioxidant activities compared using LDL in vitro oxidation assay were increased more expressively after treatment with KF(2) in both crops. PMID:19209908

  3. PGE2 Reduces MMP-14 and Increases Plasminogen Activator Inhibitor-1 in Cardiac Fibroblasts

    PubMed Central

    Kassem, Kamal M.; Clevenger, Margarette H.; Szandzik, David L.; Peterson, Edward; Harding, Pamela

    2014-01-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating towards 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  4. Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

    PubMed

    Dhuria, Shyeilla V; Fine, Jared M; Bingham, Deborah; Svitak, Aleta L; Burns, Rachel B; Baillargeon, Amanda M; Panter, Scott S; Kazi, Abdul N; Frey, William H; Hanson, Leah R

    2016-08-01

    Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors. PMID:27264485

  5. Amphetamine sensitization is accompanied by an increase in prelimbic cortex activity.

    PubMed

    Aguilar-Rivera, M I; Casanova, J P; Gatica, R I; Quirk, G J; Fuentealba, J A

    2015-03-12

    Drug addiction is associated with dysfunction in the medial prefrontal cortex (mPFC). However, the modifications of neuronal activity in mPFC underlying the reinforcing properties of addictive drugs are still unclear. Here we carried out single-unit recording experiments to study the neuronal activity in the prelimbic (PL) cortex of anesthetized rats, after expression of locomotor sensitization to amphetamine. In control rats, an acute injection of amphetamine induced mainly an inhibitory effect on firing rate (FR) and this response was negatively correlated with the basal FR. Sensitized rats showed a higher proportion of excited neurons and the response to amphetamine was independent of basal FR. Moreover, in control rats, acute amphetamine decreased burst rate, whereas in sensitized rats acute amphetamine increased burst rate. These findings indicate that amphetamine sensitization renders mPFC neurons hyperexcitable. Taken together, these data support the hypothesis that early withdrawal is associated with an increase in the activity of the mPFC, which could strengthen the PL-Nucleus Accumbens connection, thus facilitating amphetamine-induced locomotor sensitization. PMID:25542419

  6. Increased skeletal muscle glucose uptake by rosemary extract through AMPK activation.

    PubMed

    Naimi, Madina; Tsakiridis, Theodoros; Stamatatos, Theocharis C; Alexandropoulos, Dimitris I; Tsiani, Evangelia

    2015-04-01

    Stimulation of the energy sensor AMP-activated kinase (AMPK) has been viewed as a targeted approach to increase glucose uptake by skeletal muscle and control blood glucose homeostasis. Rosemary extract (RE) has been reported to activate AMPK in hepatocytes and reduce blood glucose levels in vivo but its effects on skeletal muscle are not known. In the present study, we examined the effects of RE and the mechanism of regulation of glucose uptake in muscle cells. RE stimulated glucose uptake in L6 myotubes in a dose- and time-dependent manner. Maximum stimulation was seen with 5 μg/mL of RE for 4 h (184% ± 5.07% of control, p < 0.001), a response comparable to maximum insulin (207% ± 5.26%, p < 0.001) and metformin (216% ± 8.77%, p < 0.001) stimulation. RE did not affect insulin receptor substrate 1 and Akt phosphorylation but significantly increased AMPK and acetyl-CoA carboxylase phosphorylation. Furthermore, the RE-stimulated glucose uptake was significantly reduced by the AMPK inhibitor compound C, but remained unchanged by the PI3K inhibitor, wortmannin. RE did not affect GLUT4 or GLUT1 glucose transporter translocation in contrast with a significant translocation of both transporters seen with insulin or metformin treatment. Our study is the first to show a direct effect of RE on muscle cell glucose uptake by a mechanism that involves AMPK activation. PMID:25794239

  7. PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts.

    PubMed

    Kassem, Kamal M; Clevenger, Margarette H; Szandzik, David L; Peterson, Edward; Harding, Pamela

    2014-10-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  8. Design of a new warhead for the natural enediyne dynemicin A. An increase of biological activity.

    PubMed

    Kraka, Elfi; Tuttle, Tell; Cremer, Dieter

    2008-03-01

    A concept for designing nontoxic enediyne-based antitumor drugs that was previously suggested (J. Am. Chem. Soc. 2000, 122, 8245) is converted into reality by merging amidines with the natural enediyne dynemicin A. The dynemicin-amidines (DADs) resulting from this combination are biologically not active because they form extremely labile singlet biradicals that can no longer abstract H from DNA. However, if protonated in the acidic environment of the tumor cell, they possess increased biological activity, as is reflected by a lowering of the activation enthalpy for the Bergman cyclization from 16.7 (dynemicin A) to 11-12 kcal/mol (DADs), kinetic stability of the singlet biradicals formed in the cyclization reaction, increased H abstraction ability of the singlet biradicals, and improved docking properties in the minor groove of the duplex 10-mer B-DNA sequence d(CTACTACTGG).d(CCAGTAGTAG) throughout the triggering and Bergman reactions. The implications and the consequences of using DADs to exploit the differences between normal and tumor cells and to design a nontoxic antitumor drugs are discussed. PMID:18269275

  9. Music and Methamphetamine: Conditioned Cue-induced Increases in Locomotor Activity and Dopamine Release in Rats

    PubMed Central

    Polston, J.E.; Rubbinaccio, H.Y.; Morra, J.T.; Sell, E.M.; Glick, S.D.

    2011-01-01

    Associations between drugs of abuse and cues facilitate the acquisition and maintenance of addictive behaviors. Although significant research has been done to elucidate the role that simple discriminative or discrete conditioned stimuli (e.g., a tone or a light) play in addiction, less is known about complex environmental cues. The purpose of the present study was to examine the role of a musical conditioned stimulus by assessing locomotor activity and in vivo microdialysis. Two groups of rats were given non-contingent injections of methamphetamine (1.0 mg/kg) or vehicle and placed in standard conditioning chambers. During these conditioning sessions both groups were exposed to a continuous conditioned stimulus, in the form of a musical selection (“Four” by Miles Davis) played repeatedly for ninety minutes. After seven consecutive conditioning days subjects were given one day of rest, and subsequently tested for locomotor activity or dopamine release in the absence of drug while the musical conditioned stimulus was continually present. The brain regions examined included the basolateral amygdala, nucleus accumbens, and prefrontal cortex. The results show that music is an effective contextual conditioned stimulus, significantly increasing locomotor activity after repeated association with methamphetamine. Furthermore, this musical conditioned stimulus significantly increased extracellular dopamine levels in the basolateral amygdala and nucleus accumbens. These findings support other evidence showing the importance of these brain regions in conditioned learning paradigms, and demonstrate that music is an effective conditioned stimulus warranting further investigation. PMID:21145911

  10. Apolipoprotein a1 increases mitochondrial biogenesis through AMP-activated protein kinase.

    PubMed

    Song, Parkyong; Kwon, Yonghoon; Yea, Kyungmoo; Moon, Hyo-Youl; Yoon, Jong Hyuk; Ghim, Jaewang; Hyun, Hyunjung; Kim, Dayea; Koh, Ara; Berggren, Per-Olof; Suh, Pann-Ghill; Ryu, Sung Ho

    2015-09-01

    Apolipoprotein a1, which is a major lipoprotein component of high-density lipoprotein (HDL), was reported to decrease plasma glucose in type 2 diabetes. Although recent studies also have shown that apolipoprotein a1 is involved in triglyceride (TG) metabolism, the mechanisms by which apolipoprotein a1 modulates TG levels remain largely unexplored. Here we demonstrated that apolipoprotein a1 increased mitochondrial DNA and mitochondria contents through sustained AMPK activation in myotubes. This resulted in enhanced fatty acid oxidation and attenuation of free fatty acid-induced insulin resistance features in skeletal muscle. The increment of mitochondria was mediated through induction of transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear transcription factor 1 (NRF-1). The inhibition of AMPK by a pharmacological agent inhibited the induction of mitochondrial biogenesis. Increase of AMPK phosphorylation by apolipoprotein a1 occurs through activation of upstream kinase LKB1. Finally, we confirmed that scavenger receptor Class B, type 1 (SR-B1) is an important receptor for apolipoprotein a1 in stimulating AMPK pathway and mitochondrial biogenesis. Our study suggests that apolipoprotein a1 can alleviate obesity related metabolic disease by inducing AMPK dependent mitochondrial biogenesis. PMID:25982508

  11. Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

    PubMed

    Moisala, M; Salmela, V; Hietajärvi, L; Salo, E; Carlson, S; Salonen, O; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

    2016-07-01

    The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings. PMID:27063068

  12. Increased neuroplasticity and hippocampal microglia activation in a mice model of rapid antidepressant treatment.

    PubMed

    Muzio, Luca; Brambilla, Valentina; Calcaterra, Lorenza; D'Adamo, Patrizia; Martino, Gianvito; Benedetti, Francesco

    2016-09-15

    The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects. Unbiased evaluation of the transcriptional responses were obtained in the hippocampus by Illumina Bead Chip Array system, then confirmed with real time PCR. Spine densities in granular neurons of the dentate gyrus (DG) were assayed by standard Golgi staining. Activation of Microglial/Macrophages cells was evaluated by immunufluorescence analysis for Iba1. Rates of cell proliferation was estimated pulsing mice with the S-phase tracer 5-Iodo-2'-deoxyuridine (IdU). All SD procedures caused a decreasing of floating time at FST, and increased expression of the immediate early gene Arc/Arg3.1. In addition, SSW also increased expression of the Microglia/Macrophages genes Iba-1 and chemokine receptors Cx3cR1 and CxcR4, of the canonical Wnt signaling gene Wnt7a, and of dendritic spines in CA4 neurons of the DG. SSW up-regulated both the number of Iba1+ cells and rates of cell proliferation in the subgranular region of the DG. The antidepressant-like effects of SD dissociated both, from hippocampal neuroplasticity in the DG (not occurring after ASD), and from microglial activation (not preventing behavioral response when occurring). The increase in dendritic spine density in the DG after SD and exercise was associated with an up-regulation of Wnt 7a, and with activation of the innate immune system of the brain. Increased Arc/Arg3.1 suggests however increased neuroplasticity, which could be common to all fast-acting antidepressants

  13. Calculator Function Approximation.

    ERIC Educational Resources Information Center

    Schelin, Charles W.

    1983-01-01

    The general algorithm used in most hand calculators to approximate elementary functions is discussed. Comments on tabular function values and on computer function evaluation are given first; then the CORDIC (Coordinate Rotation Digital Computer) scheme is described. (MNS)

  14. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    PubMed Central

    2012-01-01

    Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD). Methods In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I

  15. Glucocorticoids increase adipocytes in muscle by affecting IL-4 regulated FAP activity

    PubMed Central

    Dong, Yanjun; Silva, Kleiton Augusto Santos; Dong, Yanlan; Zhang, Liping

    2014-01-01

    An increase in intramuscular adipocyte tissue (IMAT) is associated with glucose dysregulation, decreased muscle strength, and increased risk of disability. Unfortunately, the mechanisms stimulating intramuscular adipogenesis remain unclear. We found that dexamethasone (Dex) administration to mice with injured muscles stimulates the accumulation of IMAT. To identify precursors of these adipocytes, we isolated satellite cells and fibro/adipogenic progenitors (FAPs) from muscle; satellite cells did not differentiate into adipocytes even following Dex treatment. In contrast, Dex stimulated FAP differentiation into adipocytes. In vivo, we transplanted purified FAPs from transgenic, EGFP mice into the injured muscles of C57/BL6 mice and found that Dex administration stimulated adipogenesis from FAP-EGFP. The increase in adipogenesis depended on Dex-induced inhibition of interleukin-4 (IL-4). In the injured muscle of IL-4-knockout mice, the levels of adipocytes were increased, while in the injured muscles of Dex-treated mice with IL-4 injections, adipogenesis was suppressed. In cultured FAPs, IL-4 inhibited Dex-induced conversion of FAPs into adipocytes; this did not occur in FAPs expressing knockdown of the IL-4 receptor. Thus, we concluded that glucocorticoids stimulate FAPs to differentiate into adipocytes in injured muscles. This process is blocked by IL-4, suggesting that interfering with IL-4 signaling could prevent adipogenesis in muscle.—Dong, Y., Silva, K. A. S., Dong, Y., Zhang, L. Glucocorticoids increase adipocytes in muscle by affecting IL-4 regulated FAP activity. PMID:24948596

  16. Increased activity of tyrosine hydroxylase in the cerebellum of the x-irradiated dystonic rat

    SciTech Connect

    Dopico, A.M.; Rios, H.; Mayo, J.; Zieher, L.M. )

    1990-08-01

    The exposure of the cephalic end of rats to repeated doses of x-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 {plus minus} 4 ng/CE and 2.8 {plus minus} 1.5 ng/CE, respectively) and x-irradiated rats (17.1 {plus minus} 1 ng/CE and 8.3 {plus minus} 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally x-irradiated animals when compared to age-matched controls (16.4 {plus minus} 1.4 vs 6.32 {plus minus} 0.6 nmol CO2/h/mg prot., p less than 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 {plus minus} 23.8 vs 408.2 {plus minus} 21.5 nmol CO2/h/CE, p less than 0.01 (controls and x-treated, respectively). These results suggest that x-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.

  17. Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT.

    PubMed

    Fang, Fang; Peng, Ting; Yang, Shiming; Wang, Weixi; Zhang, Yinong; Li, He

    2016-08-01

    Huntington's disease (HD) is an inherited neurodegenerative disease that is caused by the abnormal expansion of CAG repeats in the gene encoding huntingtin (Htt). Reduced AKT phosphorylation and inhibited AKT activity have been shown to be involved in mutant Htt (mHtt)-induced cell death. Lycium barbarum polysaccharide (LBP), the main bioactive component of Lycium barbarum, reportedly has neuroprotective roles in neural injuries, including neurodegenerative diseases. Here, we report that treatment with LBP can increased the viability of HEK293 cells that stably expressed mHtt containing 160 glutamine repeats and significantly improved motor behavior and life span in HD-transgenic mice. Furthermore, we found that in LBP-treated HEK293 cells expressing mHtt, mHtt levels were reduced and the phosphorylation of AKT at Ser473 (p-AKT-Ser473) was significantly increased. We also found that treatment with LBP increased p-AKT-Ser473 and decreased mHtt in the cortex, hippocampus and striatum in HD-transgenic mice. The level of phosphorylation of p-GSK3β-Ser9 remained unchanged in both cultured cells and HD-transgenic mice. Our findings suggest that LBP alleviates the cytotoxicity of mHtt by activating AKT and reducing mHtt levels, indicating that LBP may be potentially useful for treating HD. PMID:27196502

  18. mTORC1 signaling activates NRF1 to increase cellular proteasome levels

    PubMed Central

    Zhang, Yinan; Manning, Brendan D

    2015-01-01

    Defects in the maintenance of protein homeostasis, or proteostasis, has emerged as an underlying feature of a variety of human pathologies, including aging-related diseases. Proteostasis is achieved through the coordinated action of cellular systems overseeing amino acid availability, mRNA translation, protein folding, secretion, and degradation. The regulation of these distinct systems must be integrated at various points to attain a proper balance. In a recent study, we found that the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway, well known to enhance the protein synthesis capacity of cells while concordantly inhibiting autophagy, promotes the production of more proteasomes. Activation of mTORC1 genetically, through loss of the tuberous sclerosis complex (TSC) tumor suppressors, or physiologically, through growth factors or feeding, stimulates a transcriptional program involving the sterol-regulatory element binding protein 1 (SREBP1) and nuclear factor erythroid-derived 2-related factor 1 (NRF1; also known as NFE2L1) transcription factors leading to an increase in cellular proteasome content. As discussed here, our findings suggest that this increase in proteasome levels facilitates both the maintenance of proteostasis and the recovery of amino acids in the face of an increased protein load consequent to mTORC1 activation. We also consider the physiological and pathological implications of this unexpected new downstream branch of mTORC1 signaling. PMID:26017155

  19. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  20. Hyperthermia does not alter the increase in cerebral perfusion during cognitive activation

    PubMed Central

    Schlader, Zachary J.; Lucas, Rebekah A. I.; Pearson, James; Crandall, Craig G.

    2016-01-01

    This study tested the hypothesis that hyperthermia attenuates the increase in cerebral perfusion during cognitive activation. Mean middle cerebral artery blood velocity (MCAVmean) served as an index of cerebral perfusion, while the nBack test (a test of working memory) was the cognitive task. Hyperthermia was characterized by elevations (P < 0.001) in skin (by 5.0 ± 0.8°C) and intestinal temperatures (by 1.3 ± 0.1°C) and reductions (P < 0.020) in mean arterial pressure (by 11 ± 10 mmHg), end-tidal CO2 tension (by 3 ± 6 mmHg) and MCAVmean (by 10 ± 9 cm s−1). Hyperthermia had no influence on nBack test performance (mean difference from normothermia to hyperthermia, −1 ± 11%; P = 0.276) or, counter to the hypothesis, the increase in MCAVmean during nBack testing (mean difference from normothermia to hyperthermia: 0 ± 16 cm s−1; P = 0.608). These findings indicate that the capacity to increase cerebral perfusion during cognitive activation is unaffected by hyperthermia. PMID:23851918

  1. Increase of plasma renin activity in male and female rabbits subjected to dysbaric conditions

    NASA Technical Reports Server (NTRS)

    Chryssanthou, C.; Kircikoglu, H.; Strugar, J.

    1985-01-01

    The renin-angiotensin-aldosterone system may be implicated in hemodynamic alterations occurring in dysbaric disorders. This report concerns changes in plasma renin activity (PRA) induced by exposure of rabbits to a compression-decompression schedule that does not normally produce clinical manifestations of decompression sickness. The results revealed a significant increase in PRA in 19 of 23 animals following dysbaric exposure. Mean PRA rose from 1.18 ng ang I/ml hr (preexposure) to 2.40 ng ang I/ml hr (postexposure). The increase was particularly pronounced in female animals (217 percent). Asymptomatic intravascular gas bubbles (silent bubbles) were detected by gross or microscopic examination in the majority of the animals. Renin elaboration and secretion in asymptomatic dysbaric exposures may be mediated by bradykinin and/or prostaglandins released or activated in a chain reaction triggered by silent gas bubbles. This hypothesis is also applicable to increased PRA in altitude decompression. Alternatively elevation of PRA may result from decreased renal perfusion when dysbaric disorders are complicated by significant hypovolemia.

  2. Cellular immune activity in response to increased training of elite oarsmen prior to Olympic competition.

    PubMed

    Jakeman, P M; Weller, A; Warrington, G

    1995-06-01

    This study investigated the changes in urinary neopterin, a biochemical marker of cellular immune activity, in elite male rowers undertaking a progressive increase in training prior to Olympic competition. Twenty-seven male rowers of the 1992 Great Britain team provided daily urine samples for a 4-week period of training that included 17 days of altitude training and 10 days of heat acclimatization. The mean (+/- S.D.) ratio of neopterin/creatinine in urine increased from pre-training values of 135 +/- 32 to a peak of 219 +/- 121 mumol neopterin per mol creatinine on day 19 of training (P < 0.05). Changes in the ratio of neopterin/creatinine with training were found to be transient and highly variable between subjects, ranging from no change to peak values five-fold greater than baseline. On the basis of the in vivo measurement of cell-mediated immunity employed in this study, we conclude that elite athletes engaged in high-intensity training prior to competition show either no change or a moderate increase in cellular immune activation. PMID:7563287

  3. Antibacterial activity and increased freeze-drying stability of sialyllactose-reduced silver nanoparticles using sucrose and trehalose.

    PubMed

    Noh, Hwa Jung; Im, A-Rang; Kim, Hyun-Seok; Sohng, Jae Kyung; Kim, Chong-Kook; Kim, Yeong Shik; Cho, Seonho; Park, Youmie

    2012-05-01

    The resistance to current antibiotics results in the emergence of health-threatening bacteria. Silver nanoparticles are known to exhibit broad-spectrum antibacterial activities without the development of resistance. Herein, we developed a green synthetic method for the preparation of silver nanoparticles with sialyllactose instead of toxic chemicals as a reducing agent, which would improve its therapeutic applicability and increase its biocompatibility. Oven incubation, autoclaving and microwave irradiation methods were applied to prepare the silver nanoparticles. High resolution-transmission electron microscopy and atomic force microscopy images revealed mostly spherical and amorphous silver nanoparticles with an average diameter of 23.64 nm. Fourier Transform-infrared spectra suggest that the N-H amide of sialyllactose might be involved in the binding of silver nanoparticles. Based on thermogravimetric analyses, 2,3-sialyllactose-reduced silver nanoparticles are composed of 54.3 wt% organic components and 45.7 wt% metallic silver. Enhanced antibacterial activities of silver nanoparticles (approximately 8-fold) were observed against Pseudomonas aeruginosa, Escherichia coli and Salmonella typhimurium (minimum inhibitory concentration 16 microg/mL). Next, we employed the use of carbohydrate stabilizers to increase the stability of silver nanoparticles during a freeze-drying process. It was found that sucrose and trehalose were the most effective stabilizers. In addition, silver nanoparticles possessed excellent salt stability as well as on-the-shelf stability in the presence of these stabilizers. Derivatives of sialic acid are known to be anti-influenza agents; therefore, the newly prepared silver nanoparticles may serve as useful antibacterial and antiviral agents to cope with both pathogenic bacteria and viruses in the near future. PMID:22852321

  4. Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

    PubMed

    Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

    2014-11-01

    Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. PMID:25157430

  5. Clinically used selective oestrogen receptor modulators increase LDL receptor activity in primary human lymphocytes

    PubMed Central

    Cerrato, F; Fernández-Suárez, M E; Alonso, R; Alonso, M; Vázquez, C; Pastor, O; Mata, P; Lasunción, M A; Gómez-Coronado, D

    2015-01-01

    Background and Purpose Treatment with selective oestrogen receptor modulators (SERMs) reduces low-density lipoprotein (LDL) cholesterol levels. We assessed the effect of tamoxifen, raloxifene and toremifene and their combinations with lovastatin on LDL receptor activity in lymphocytes from normolipidaemic and familial hypercholesterolaemic (FH) subjects, and human HepG2 hepatocytes and MOLT-4 lymphoblasts. Experimental Approach Lymphocytes were isolated from peripheral blood, treated with different compounds, and 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanine perchlorate (DiI)-labelled LDL uptake was analysed by flow cytometry. Key Results Tamoxifen, toremifene and raloxifene, in this order, stimulated DiI-LDL uptake by lymphocytes by inhibiting LDL-derived cholesterol trafficking and subsequent down-regulation of LDL receptor expression. Differently to what occurred in HepG2 and MOLT-4 cells, only tamoxifen consistently displayed a potentiating effect with lovastatin in primary lymphocytes. The SERM-mediated increase in LDL receptor activity was not altered by the anti-oestrogen ICI 182 780 nor was it reproduced by 17β-oestradiol. However, the tamoxifen-active metabolite endoxifen was equally effective as tamoxifen. The SERMs produced similar effects on LDL receptor activity in heterozygous FH lymphocytes as in normal lymphocytes, although none of them had a potentiating effect with lovastatin in heterozygous FH lymphocytes. The SERMs had no effect in homozygous FH lymphocytes. Conclusions and Implications Clinically used SERMs up-regulate LDL receptors in primary human lymphocytes. There is a mild enhancement between SERMs and lovastatin of lymphocyte LDLR activity, the potentiation being greater in HepG2 and MOLT-4 cells. The effect of SERMs is independent of oestrogen receptors but is preserved in the tamoxifen-active metabolite endoxifen. This mechanism may contribute to the cholesterol-lowering action of SERMs. PMID:25395200

  6. 2,4,6-Trichlorophenol mediated increases in extracellular peroxidase activity in three species of Lemnaceae.

    PubMed

    Biswas, Dilip K; Scannell, Gillian; Akhmetov, Nurlan; Fitzpatrick, Dara; Jansen, Marcel A K

    2010-11-01

    Chlorinated phenols, or chlorophenols, are persistent priority pollutants that are widespread in the environment. Class III peroxidases are well-characterised plant enzymes that can catalyse the oxidative dechlorination of chlorophenols. Expression of these enzymes by plants is commonly associated with plant stress, therefore limiting scope for phytoremediation. In this study, we have quantitatively compared peroxidase activity and phytotoxicity as a function of 2,4,6-trichlorophenol (TCP) concentration in three species of Lemnaceae; Lemna minor, Lemna gibba and Landoltia punctata. Effects of TCP on the growth rates of the three species differed considerably with L. punctata being the most tolerant species. TCP also affected photosynthetic parameters, causing a decrease in open photosystem II reaction centres (qP) and, in L. punctata only, a decrease in non-photochemical quenching (qN). In parallel, TCP exposure resulted in increased peroxidase activity in all three species. Peroxidase activity in L. minor and L. gibba displayed an inverse relationship with biomass accumulation, i.e. the more growth reduction the more peroxidase activity. In contrast, induction of peroxidase activity in L. punctata was bi-phasic, with a TCP-induced activity peak at concentrations that had no major effect on growth, and further induction under phytotoxic concentrations. The mechanism by which L. punctata recognises and responds to low concentrations of an anthropogenic compound, in the absence of wide-ranging stress, remains enigmatic. However, we conclude that this "window" of peroxidase production in the absence of major growth inhibition offers potential for the development of sustainable, peroxidise-mediated phytoremediation systems. PMID:20810175

  7. Intestinal NADPH oxidase 2 activity increases in a neonatal rat model of necrotizing enterocolitis.

    PubMed

    Welak, Scott R; Rentea, Rebecca M; Teng, Ru-Jeng; Heinzerling, Nathan; Biesterveld, Ben; Liedel, Jennifer L; Pritchard, Kirkwood A; Fredrich, Katherine M; Gourlay, David M

    2014-01-01

    Necrotizing enterocolitis (NEC) is a complication of prematurity. The etiology is unknown, but is related to enteral feeding, ischemia, infection, and inflammation. Reactive oxygen species production, most notably superoxide, increases in NEC. NADPH oxidase (NOX) generates superoxide, but its activity in NEC remains unknown. We hypothesize that NOX-derived superoxide production increases in NEC. Newborn Sprague-Dawley rats were divided into control, formula-fed, formula/LPS, formula/hypoxia, and NEC (formula, hypoxia, and LPS). Intestinal homogenates were analyzed for NADPH-dependent superoxide production. Changes in superoxide levels on days 0-4 were measured. Inhibitors for nitric oxide synthase (L-NAME) and NOX2 (GP91-ds-tat) were utilized. RT-PCR for eNOS, NOX1, GP91phox expression was performed. Immunofluorescence studies estimated the co-localization of p47phox and GP91phox in control and NEC animals on D1, D2, and D4. NEC pups generated more superoxide than controls on D4, while all other groups were unchanged. NADPH-dependent superoxide production was greater in NEC on days 0, 3, and 4. GP91-ds-tat decreased superoxide production in both groups, with greater inhibition in NEC. L-NAME did not alter superoxide production. Temporally, superoxide production varied minimally in controls. In NEC, superoxide generation was decreased on day 1, but increased on days 3-4. GP91phox expression was higher in NEC on days 2 and 4. NOX1 and eNOS expression were unchanged from controls. GP91phox and p47phox had minimal co-localization in all control samples and NEC samples on D1 and D2, but had increased co-localization on D4. In conclusion, this study proves that experimentally-induced NEC increases small intestinal NOX activity. All components of NEC model are necessary for increased NOX activity. NOX2 is the major source, especially as the disease progresses. PMID:25517730

  8. Approximate spatial reasoning

    NASA Technical Reports Server (NTRS)

    Dutta, Soumitra

    1988-01-01

    Much of human reasoning is approximate in nature. Formal models of reasoning traditionally try to be precise and reject the fuzziness of concepts in natural use and replace them with non-fuzzy scientific explicata by a process of precisiation. As an alternate to this approach, it has been suggested that rather than regard human reasoning processes as themselves approximating to some more refined and exact logical process that can be carried out with mathematical precision, the essence and power of human reasoning is in its capability to grasp and use inexact concepts directly. This view is supported by the widespread fuzziness of simple everyday terms (e.g., near tall) and the complexity of ordinary tasks (e.g., cleaning a room). Spatial reasoning is an area where humans consistently reason approximately with demonstrably good results. Consider the case of crossing a traffic intersection. We have only an approximate idea of the locations and speeds of various obstacles (e.g., persons and vehicles), but we nevertheless manage to cross such traffic intersections without any harm. The details of our mental processes which enable us to carry out such intricate tasks in such apparently simple manner are not well understood. However, it is that we try to incorporate such approximate reasoning techniques in our computer systems. Approximate spatial reasoning is very important for intelligent mobile agents (e.g., robots), specially for those operating in uncertain or unknown or dynamic domains.

  9. Approximate kernel competitive learning.

    PubMed

    Wu, Jian-Sheng; Zheng, Wei-Shi; Lai, Jian-Huang

    2015-03-01

    Kernel competitive learning has been successfully used to achieve robust clustering. However, kernel competitive learning (KCL) is not scalable for large scale data processing, because (1) it has to calculate and store the full kernel matrix that is too large to be calculated and kept in the memory and (2) it cannot be computed in parallel. In this paper we develop a framework of approximate kernel competitive learning for processing large scale dataset. The proposed framework consists of two parts. First, it derives an approximate kernel competitive learning (AKCL), which learns kernel competitive learning in a subspace via sampling. We provide solid theoretical analysis on why the proposed approximation modelling would work for kernel competitive learning, and furthermore, we show that the computational complexity of AKCL is largely reduced. Second, we propose a pseudo-parallelled approximate kernel competitive learning (PAKCL) based on a set-based kernel competitive learning strategy, which overcomes the obstacle of using parallel programming in kernel competitive learning and significantly accelerates the approximate kernel competitive learning for large scale clustering. The empirical evaluation on publicly available datasets shows that the proposed AKCL and PAKCL can perform comparably as KCL, with a large reduction on computational cost. Also, the proposed methods achieve more effective clustering performance in terms of clustering precision against related approximate clustering approaches. PMID:25528318

  10. Role of membrane depolarization and extracellular calcium in increased complement receptor expression during neutrophil (PMN) activation

    SciTech Connect

    Berger, M.; Wetzler, E.; Birx, D.L.

    1986-03-05

    During PMN activation the surface expression of receptors (R) for C3b and C3bi increases rapidly. This is necessary for optimal cell adhesion, migration, and phagocytosis. Following stimulation with fMLP or LTB-4, the increased expression of C3bR depends only on the Ca/sup + +/ released from intracellular stores and is not inhibited by 5mM EDTA, while the increase in C3biR also requires extracellular Ca/sup + +/. CR expression also increases when the PMN are depolarized with 140 mM K/sup +/, but with this stimulus, EDTA inhibits C3bR by 67% and C3biR 100%, suggesting that intracellular Ca/sup + +/ stores may not be released. Pertussis toxin caused dose-dependent inhibition of both CR responses to fMLP and also inhibited the increases in both CR induced by K/sup +/. Membrane depolarization (monitored by di-O-C5 fluorescence) due to fMLP was similarly inhibited by toxin but the depolarization due to K/sup +/ was not. The dose of phorbol myristate acetate that maximally increased CR expression, 0.1 ng/ml, did not depolarize the membrane. These results suggest that membrane depolarization is neither necessary nor sufficient for increased CR expression. A Ca/sup + +/ and GTP binding protein-dependent enzyme such as phospholipase C is necessary to the amplify initial signals generated either by release of Ca/sup + +/ stores or by opening voltage dependent Ca/sup + +/ channels following membrane depolarization.

  11. Organelle size control - increasing vacuole content activates SNAREs to augment organelle volume through homotypic fusion.

    PubMed

    Desfougères, Yann; Neumann, Heinz; Mayer, Andreas

    2016-07-15

    Cells control the size of their compartments relative to cell volume, but there is also size control within each organelle. Yeast vacuoles neither burst nor do they collapse into a ruffled morphology, indicating that the volume of the organellar envelope is adjusted to the amount of content. It is poorly understood how this adjustment is achieved. We show that the accumulating content of yeast vacuoles activates fusion of other vacuoles, thus increasing the volume-to-surface ratio. Synthesis of the dominant compound stored inside vacuoles, polyphosphate, stimulates binding of the chaperone Sec18/NSF to vacuolar SNAREs, which activates them and triggers fusion. SNAREs can only be activated by lumenal, not cytosolic, polyphosphate (polyP). Control of lumenal polyP over SNARE activation in the cytosol requires the cytosolic cyclin-dependent kinase Pho80-Pho85 and the R-SNARE Nyv1. These results suggest that cells can adapt the volume of vacuoles to their content through feedback from the vacuole lumen to the SNAREs on the cytosolic surface of the organelle. PMID:27252384

  12. Increased riboflavin production from activated bleaching earth by a mutant strain of Ashbya gossypii.

    PubMed

    Tajima, Satoshi; Itoh, Yoko; Sugimoto, Takashi; Kato, Tatsuya; Park, Enoch Y

    2009-10-01

    The production of riboflavin from vegetable oil was increased using a mutant strain of Ashbya gossypii. This mutant was generated by treating the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Riboflavin production was 10-fold higher in the mutant compared to the wild-type strain. The specific intracellular catalase activity after 3 d of culture was 6-fold higher in the mutant than in the wild-type strain. For the mutant, riboflavin production in the presence of 40 mM hydrogen peroxide was 16% less than that in the absence of hydrogen peroxide, whereas it was 56% less for the wild-type strain. The isocitrate lyase (ICL) activity of the mutant was 0.26 mU/mg of protein during the active riboflavin production phase, which was 2.6-fold higher than the wild-type strain. These data indicate that the mutant utilizes the carbon flux from the TCA cycle to the glyoxylate cycle more efficiently than the wild-type strain, resulting in enhanced riboflavin production. This novel mutant has the potential to be of use for industrial-scale riboflavin production from waste-activated bleaching earth (ABE), thereby transforming a useless material into a valuable bioproduct. PMID:19716523

  13. Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

    SciTech Connect

    Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S. )

    1990-01-01

    Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly.

  14. Overexpression of a cuticle-degrading protease Ver112 increases the nematicidal activity of Paecilomyces lilacinus.

    PubMed

    Yang, Jinkui; Zhao, Xuna; Liang, Lianming; Xia, Zhenyuan; Lei, Liping; Niu, Xuemei; Zou, Chenggang; Zhang, Ke-Qin

    2011-03-01

    Due to their ability to degrade the proteins in nematode cuticle, serine proteases play an important role in the pathogenicity of nematophagous fungi against nematodes. The serine protease Ver112 was identified from the nematophagous fungus Lecanicillium psalliotae capable of degrading the nematode cuticle and killing nematodes effectively. In this study, the gene ver112 was introduced into the commercial biocontrol fungal agent Paecilomyces lilacinus by the restriction enzyme-mediated integration transformation. Compared to the wild strain, the transformant P. lilacinus 112 showed significantly greater protease activity, with nematicidal activities increased by 79% and 96% to Panagrellus redivivus and Caenorhabditis elegans at the second day, respectively. The crude protein extract isolated from the culture filtrate of P. lilacinus 112 also showed 20-25% higher nematicidal activity than that of the wild-type strain. Reverse transcription PCR results showed that the expression of gene ver112 in P. lilacinus 112 was correlated to protease activity of the culture filtrate. Our results demonstrated the first successful transfer of a virulence gene from one nematophagous fungus to another nematophagous fungus, and improved the pathogenicity of the recipient fungus against pest nematodes. PMID:21110018

  15. 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

  16. Active control of noise on the source side of a partition to increase its sound isolation

    NASA Astrophysics Data System (ADS)

    Tarabini, Marco; Roure, Alain; Pinhede, Cedric

    2009-03-01

    This paper describes a local active noise control system that virtually increases the sound isolation of a dividing wall by means of a secondary source array. With the proposed method, sound pressure on the source side of the partition is reduced using an array of loudspeakers that generates destructive interference on the wall surface, where an array of error microphones is placed. The reduction of sound pressure on the incident side of the wall is expected to decrease the sound radiated into the contiguous room. The method efficiency was experimentally verified by checking the insertion loss of the active noise control system; in order to investigate the possibility of using a large number of actuators, a decentralized FXLMS control algorithm was used. Active control performances and stability were tested with different array configurations, loudspeaker directivities and enclosure characteristics (sound source position and absorption coefficient). The influence of all these parameters was investigated with the factorial design of experiments. The main outcome of the experimental campaign was that the insertion loss produced by the secondary source array, in the 50-300 Hz frequency range, was close to 10 dB. In addition, the analysis of variance showed that the active noise control performance can be optimized with a proper choice of the directional characteristics of the secondary source and the distance between loudspeakers and error microphones.

  17. Cellular and circuit models of increased resting-state network gamma activity in schizophrenia.

    PubMed

    White, R S; Siegel, S J

    2016-05-01

    Schizophrenia (SCZ) is a disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, reduced sociability, and anhedonia), as well as persistent cognitive deficits (memory, concentration, and learning). While the biology underlying subjective experiences is difficult to study, abnormalities in electroencephalographic (EEG) measures offer a means to dissect potential circuit and cellular changes in brain function. EEG is indispensable for studying cerebral information processing due to the introduction of techniques for the decomposition of event-related activity into its frequency components. Specifically, brain activity in the gamma frequency range (30-80Hz) is thought to underlie cognitive function and may be used as an endophenotype to aid in diagnosis and treatment of SCZ. In this review we address evidence indicating that there is increased resting-state gamma power in SCZ. We address how modeling this aspect of the illness in animals may help treatment development as well as providing insights into the etiology of SCZ. PMID:26577758

  18. A girl with increased writing and painting activities associated with Turner's syndrome and autistic spectrum disorder.

    PubMed

    Ahouee, Shohreh Mohseni; Shooshtari, Mitra Hakim; Bidaki, Reza

    2015-01-01

    This report describes the findings on the evaluation of a 9-year-old girl with disabling and pronounced increased writing and painting activities associated with Turner's syndrome and autistic spectrum disorder. She spent most of the time doing these activities which affected not only her academic performance, but also social relationships. A comprehensive treatment plan consists of both biological and psychological aspects, is the main point of this case. Low dose of risperidone (0.5 mg/day) was started to decrease the patient's stereotypic behaviors. Sertraline (12.5 mg/day) was prescribed for her phobia. She was also referred to an occupational therapist in order to improve her social skills. PMID:26015917

  19. Artemisinins, new miconazole potentiators resulting in increased activity against Candida albicans biofilms.

    PubMed

    De Cremer, Kaat; Lanckacker, Ellen; Cools, Tanne L; Bax, Marijke; De Brucker, Katrijn; Cos, Paul; Cammue, Bruno P A; Thevissen, Karin

    2015-01-01

    Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albicans biofilm-related infections. PMID:25367916

  20. Cueing vocabulary during sleep increases theta activity during later recognition testing.

    PubMed

    Schreiner, Thomas; Göldi, Maurice; Rasch, Björn

    2015-11-01

    Neural oscillations in the theta band have repeatedly been implicated in successful memory encoding and retrieval. Several recent studies have shown that memory retrieval can be facilitated by reactivating memories during their consolidation during sleep. However, it is still unknown whether reactivation during sleep also enhances subsequent retrieval-related neural oscillations. We have recently demonstrated that foreign vocabulary cues presented during sleep improve later recall of the associated translations. Here, we examined the effect of cueing foreign vocabulary during sleep on oscillatory activity during subsequent recognition testing after sleep. We show that those words that were replayed during sleep after learning (cued words) elicited stronger centroparietal theta activity during recognition as compared to noncued words. The reactivation-induced increase in theta oscillations during later recognition testing might reflect a strengthening of individual memory traces and the integration of the newly learned words into the mental lexicon by cueing during sleep. PMID:26235609

  1. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

    PubMed Central

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

  2. Increased Diels-Alderase activity through backbone remodeling guided by Foldit players.

    PubMed

    Eiben, Christopher B; Siegel, Justin B; Bale, Jacob B; Cooper, Seth; Khatib, Firas; Shen, Betty W; Players, Foldit; Stoddard, Barry L; Popovic, Zoran; Baker, David

    2012-02-01

    Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems. PMID:22267011

  3. Increased antibacterial activity against Escherichia coli in bovine serum after the induction of endotoxin tolerance.

    PubMed

    Hill, A W; Shears, A L; Hibbitt, K G

    1976-07-01

    Small amounts of endotoxin injected intramuscularly into cows induced endotoxin pyrogenic tolerance and an increase in the rate at which the serum killed a strain of Escherichia coli. Most of the difference between normal serum and serum from the endotoxin-tolerant animal was shown to be due to a bentonite-adsorbable factor other than lysozyme or beta-lysin. The antibacterial activity was not completely removed from either type of serum after bentonite adsorption. Electron microscope studies and measurement of the rate of release of radioactively labeled cytoplasmic contents showed that the bentonite-adsorbable factor was important in the final breakdown of the cell membrane and release of cellular contents. The antibacterial system was totally dependent on complement, and the importance of antibodies could not be entirely ruled out because adsorption at O C with homologous cells eliminated the killing activity. PMID:780275

  4. Urinary cholinesterase activity is increased in insulin-dependent diabetics: further evidence of diabetic tubular dysfunction.

    PubMed

    Matteucci, E; Pellegrini, L; Uncini-Manganelli, C; Cecere, M; Saviozzi, M; Giampietro, O

    1992-01-01

    We measured the cholinesterase activity in morning urines from 63 insulin-dependent diabetics and 27 controls. The total esterase (TotE) activity (Ellman's method) has been divided into aliesterase (AliE), pseudocholinesterase and acetylcholinesterase by means of two inhibitors, eserine and quinidine. Diabetics were divided in 2 groups according to the urinary albumin/creatinine ratio (mg/mmol, < 2 in group 1, > 2 in group 2). The urinary cholinesterase behavior was correlated with that of a known tubular lysosomal hydrolase, N-acetyl-beta-D-glucosaminidase (NAG). Compared to normals, in addition to a significant increase in urinary NAG in diabetes (in group 2 more than in group 1), TotE and AliE were also significantly raised (+36% and 109% of the controls, in group 1 as much as in group 2). PMID:1308857

  5. Mineral supplementation increases erythrose reductase activity in erythritol biosynthesis from glycerol by Yarrowia lipolytica.

    PubMed

    Tomaszewska, Ludwika; Rymowicz, Waldemar; Rywińska, Anita

    2014-03-01

    The aim of this study was to examine the impact of divalent copper, iron, manganese, and zinc ions on the production of erythritol from glycerol by Yarrowia lipolytica and their effect on the activity of erythrose reductase. No inhibitory effect of the examined minerals on yeast growth was observed in the study. Supplementation with MnSO4 · 7H2O (25 mg l(-1)) increased erythritol production by Y. lipolytica by 14.5%. In the bioreactor culture with manganese ion addition, 47.1 g l(-1) of erythritol was produced from 100.0 g l(-1) of glycerol, which corresponded to volumetric productivity of 0.87 g l(-1) h(-1). The addition of Mn(2+) enhanced the intracellular activity of erythrose reductase up to 24.9 U g(-1) of dry weight of biomass (DW), hence, about 1.3 times more than in the control. PMID:24488778

  6. An Intense Terminal Epoch of Widespread Fluvial Activity on Early Mars: 2. Increased Runoff and Paleolake Development

    NASA Technical Reports Server (NTRS)

    Rossman III, Irwin P.; Howard, Alan D.; Craddock, Robert A.; Moore, Jeffrey M.

    2005-01-01

    To explain the much higher denudation rates and valley network development on early Mars (more than approximately 3.6 Gyr ago), most investigators have invoked either steady state warm/wet (Earthlike) or cold/dry (modern Mars) end-member paleoclimates. Here we discuss evidence that highland gradation was prolonged, but generally slow and possibly ephemeral during the Noachian Period, and that the immature valley networks entrenched during a brief terminal epoch of more erosive fluvial activity in the late Noachian to early Hesperian. Observational support for this interpretation includes (1) late-stage breaching of some enclosed basins that had previously been extensively modified, but only by internal erosion and deposition; (2) deposition of pristine deltas and fans during a late stage of contributing valley entrenchment; (3) a brief, erosive response to base level decline (which was imparted as fretted terrain developed by a suite of processes unrelated to surface runoff) in fluvial valleys that crosscut the highland-lowland boundary scarp; and (4) width/contributing area relationships of interior channels within valley networks, which record significant late-stage runoff production with no evidence of recovery to lower-flow conditions. This erosion appears to have ended abruptly, as depositional landforms generally were not entrenched with declining base level in crater lakes. A possible planetwide synchronicity and common cause to the late-stage fluvial activity are possible but remain uncertain. This increased activity of valley networks is offered as a possible explanation for diverse features of highland drainage basins, which were previously cited to support competing warm, wet and cold, dry paleoclimate scenarios.

  7. Elevated atmospheric CO2 increases microbial growth rates and enzymes activity in soil

    NASA Astrophysics Data System (ADS)

    Blagodatskaya, Evgenia; Blagodatsky, Sergey; Dorodnikov, Maxim; Kuzyakov, Yakov

    2010-05-01

    Increasing the belowground translocation of assimilated carbon by plants grown under elevated CO2 can cause a shift in the structure and activity of the microbial community responsible for the turnover of organic matter in soil. We investigated the long-term effect of elevated CO2 in the atmosphere on microbial biomass and specific growth rates in root-free and rhizosphere soil. The experiments were conducted under two free air carbon dioxide enrichment (FACE) systems: in Hohenheim and Braunschweig, as well as in the intensively managed forest mesocosm of the Biosphere 2 Laboratory (B2L) in Oracle, AZ. Specific microbial growth rates (μ) were determined using the substrate-induced respiration response after glucose and/or yeast extract addition to the soil. We evaluated the effect of elevated CO2 on b-glucosidase, chitinase, phosphatase, and sulfatase to estimate the potential enzyme activity after soil amendment with glucose and nutrients. For B2L and both FACE systems, up to 58% higher μ were observed under elevated vs. ambient CO2, depending on site, plant species and N fertilization. The μ-values increased linearly with atmospheric CO2 concentration at all three sites. The effect of elevated CO2 on rhizosphere microorganisms was plant dependent and increased for: Brassica napus=Triticum aestivumincrease or decrease of microbial growth rates depending on plant species. The μ-value increase was lower for microorganisms growing on yeast extract then for those growing on glucose, i.e. the effect of elevated CO2 was smoothed on rich vs. simple substrate. So, the r/K strategies ratio can be better revealed by studying growth on simple (glucose) than on rich substrate mixtures (yeast extract). After adding glucose, enzyme activities under elevated CO2 were

  8. Lipopolysaccharide increases cell surface P-glycoprotein that exhibits diminished activity in intestinal epithelial cells.

    PubMed

    Mishra, Jayshree; Zhang, Qiuye; Rosson, Jessica L; Moran, John; Dopp, John M; Neudeck, Brien L

    2008-10-01

    Increasingly, it is recognized that commensal microflora regulate epithelial cell processes through the dynamic interaction of pathogen-associated molecular patterns and host pattern recognition receptors such as Toll-like receptor 4 (TLR4). We therefore investigated the effects of bacterial lipopolysaccharide (LPS) on intestinal P-glycoprotein (P-gp) expression and function. Human SW480 (P-gp+/TLR4+) and Caco-2 (P-gp+/TLR4-) cells were treated with medium control or LPS (100 ng/ml) for 24 h prior to study. P-gp function was assessed by measuring the intracellular concentration of rhodamine 123 (Rh123). To confirm P-gp-specific effects, breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 2 (MRP-2/ABCC2) were also analyzed. Treatment of SW480 cells with LPS led to diminished P-gp activity, which could be prevented with polymyxin B (control: 207+/-16 versus LPS: 402+/-22 versus LPS+polymyxin B: 238+/-26 pmoles Rh123/mg protein, p<0.05 control versus LPS). These effects could be blocked by using polymyxin B and were not seen in the P-gp+/TLR4--Caco-2 cell line (control: 771+/-28 versus LPS: 775+/-59 pmoles Rh123/mg protein). Total cellular levels of P-gp did not change in LPS-treated SW480 cells; however, a significant increase in cell surface P-gp was detected. No change in activity, total protein, or apically located MRP-2 was detected following LPS treatment. Sequence analysis confirmed wild-type status of SW480 cells. These data suggest that activation of TLR4 in intestinal epithelial cells leads to an increase in plasma membrane P-gp that demonstrates a diminished capacity to transport substrate. PMID:18687802

  9. Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers.

    PubMed

    Politis, Marios; Lahiri, Nayana; Niccolini, Flavia; Su, Paul; Wu, Kit; Giannetti, Paolo; Scahill, Rachael I; Turkheimer, Federico E; Tabrizi, Sarah J; Piccini, Paola

    2015-11-01

    Previous studies have shown activation of the immune system and altered immune response in Huntington's disease (HD) gene carriers. Here, we hypothesized that peripheral and central immune responses could be concurrent pathophysiological events and represent a global innate immune response to the toxic effects of mutant huntingtin in HD gene carriers. We sought to investigate our hypothesis using [(11)C]PK11195 PET as a translocator protein (TSPO) marker of central microglial activation, together with assessment of peripheral plasma cytokine levels in a cohort of premanifest HD gene carriers who were more than a decade from predicted symptomatic conversion. Data were also compared to those from a group of healthy controls matched for age and gender. We found significantly increased peripheral plasma IL-1β levels in premanifest HD gene carriers compared to the group of normal controls (P=0.018). Premanifest HD gene carriers had increased TSPO levels in cortical, basal ganglia and thalamic brain regions (P<0.001). Increased microglial activation in somatosensory cortex correlated with higher plasma levels of IL-1β (rs=0.87, P=0.013), IL-6 (rs=0.85, P=0.013), IL-8 (rs=0.68, P=0.045) and TNF-α (rs=0.79; P=0.013). Our findings provide first in vivo evidence for an association between peripheral and central immune responses in premanifest HD gene carriers, and provide further supporting evidence for the role of immune dysfunction in the pathogenesis of HD. PMID:26297319

  10. The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo

    NASA Technical Reports Server (NTRS)

    Deruere, J.; Jackson, K.; Garbers, C.; Soll, D.; Delong, A.; Evans, M. L. (Principal Investigator)

    1999-01-01

    Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic C subunit and two distinct regulatory subunits, A and B. The RCN1 gene encodes one of three A regulatory subunits in Arabidopsis thaliana. A T-DNA insertion mutation at this locus impairs root curling, seedling organ elongation and apical hypocotyl hook formation. We have used in vivo and in vitro assays to gauge the impact of the rcn1 mutation on PP2A activity in seedlings. PP2A activity is decreased in extracts from rcn1 mutant seedlings, and this decrease is not due to a reduction in catalytic subunit expression. Roots of mutant seedlings exhibit increased sensitivity to the phosphatase inhibitors okadaic acid and cantharidin in organ elongation assays. Shoots of dark-grown, but not light-grown seedlings also show increased inhibitor sensitivity. Furthermore, cantharidin treatment of wild-type seedlings mimics the rcn1 defect in root curling, root waving and hypocotyl hook formation assays. In roots of wild-type seedlings, RCN1 mRNA is expressed at high levels in root tips, and accumulates to lower levels in the pericycle and lateral root primordia. In shoots, RCN1 is expressed in the apical hook and the basal, rapidly elongating cells in etiolated hypocotyls, and in the shoot meristem and leaf primordia of light-grown seedlings. Our results show that the wild-type RCN1-encoded A subunit functions as a positive regulator of the PP2A holoenzyme, increasing activity towards substrates involved in organ elongation and differential cell elongation responses such as root curling.

  11. Feasibility of using a compact elliptical device to increase energy expenditure during sedentary activities

    PubMed Central

    Rovniak, Liza S.; Denlinger, LeAnn; Duveneck, Ellen; Sciamanna, Christopher N.; Kong, Lan; Freivalds, Andris; Ray, Chester A.

    2013-01-01

    Objectives This study aimed to evaluate the feasibility of using a compact elliptical device to increase energy expenditure during sedentary activities. A secondary aim was to evaluate if two accelerometers attached to the elliptical device could provide reliable and valid assessments of participants’ frequency and duration of elliptical device use. Design Physically inactive adults (n = 32, age range = 25–65) were recruited through local advertisements and selected using stratified random sampling based on sex, body mass index (BMI), and age. Methods Indirect calorimetry was used to assess participants’ energy expenditure while seated and while using the elliptical device at a self-selected intensity level. Participants also self-reported their interest in using the elliptical device during sedentary activities. Two Actigraph GT3X accelerometers were attached to the elliptical device to record time-use patterns. Results Participants expended a median of 179.1 kilocalories per hour while using the elliptical device (range = 108.2–269.0), or a median of 87.9 more kilocalories (range = 19.7–178.6) than they would expend per hour of sedentary sitting. Participants reported high interest in using the elliptical device during TV watching and computer work, but relatively low interest in using the device during office meetings. Women reported greater interest in using the elliptical device than men. The two accelerometers recorded identical time-use patterns on the elliptical device and demonstrated concurrent validity with time-stamped computer records. Conclusions Compact elliptical devices could increase energy expenditure during sedentary activities, and may provide proximal environmental cues for increasing energy expenditure across multiple life domains. PMID:24035273

  12. The improvement of exercise performance by physical training is related to increased hypothalamic neuronal activation.

    PubMed

    Santiago, Henrique P; Leite, Laura H R; Lima, Paulo Marcelo A; Rodovalho, Gisele V; Szawka, Raphael E; Coimbra, Cândido C

    2016-01-01

    The effects of physical training on hypothalamic activation after exercise and their relationship with heat dissipation were investigated. Following 8 weeks of physical training, trained (TR, n = 9) and untrained (UN, n = 8) Wistar rats were submitted to a regimen of incremental running until fatigue while body and tail temperatures were recorded. After exercise, hypothalamic c-Fos immunohistochemistry analysis was performed. The workload, body-heating rate, heat storage and body temperature threshold for cutaneous vasodilation were calculated. Physical training