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Sample records for activity increased steadily

  1. Glissandi: transient fast electrocorticographic oscillations of steadily increasing frequency, explained by temporally increasing gap junction conductance

    PubMed Central

    Cunningham, Mark O.; Roopun, Anita; Schofield, Ian S.; Whittaker, Roger G.; Duncan, Roderick; Russell, Aline; Jenkins, Alistair; Nicholson, Claire; Whittington, Miles A.; Traub, Roger D.

    2012-01-01

    Purpose We describe a form of very fast oscillation (VFO) in patient electrocorticographic (ECoG) recordings, that can occur prior to ictal events, in which the frequency increases steadily from ~30–40 Hz to >120 Hz, over a period of seconds. We dub these events “glissandi” and describe a possible model for them. Methods Four patients with epilepsy had presurgical evaluations (with ECoG obtained in two of them), and excised tissue was studied in vitro, from 3 of the patients. Glissandi were seen spontaneously in vitro, associated with ictal events; using acute slices of rat neocortex; and they were simulated using a network model of 15,000 detailed layer V pyramidal neurons, coupled by gap junctions. Key findings Glissandi were observed to arise from human temporal neocortex. In vitro, they lasted 0.2 to 4.1 seconds, prior to ictal onset. Similar events were observed in the rat in vitro, in layer V of frontal neocortex, when alkaline solution was pressure-ejected; glissandi persisted when GABAA, GABAB, and NMDA and AMPA receptors were blocked. Non-alkaline conditions, prevented glissando generation. In network simulations, it was found that steadily increasing gap junction conductance would lead to the observed steady increase in VFO field frequency. This occurred because increasing gap junction conductance shortened the time required for an action potential to cross from cell to cell. Significance The in vitro and modeling data are consistent with the hypothesis that glissandi arise when pyramidal cell gap junction conductances rise over time, possibly as a result of an alkaline fluctuation in brain pH. PMID:22686654

  2. Semantic Wavelet-Induced Frequency-Tagging (SWIFT) Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas

    PubMed Central

    Koenig-Robert, Roger; VanRullen, Rufin; Tsuchiya, Naotsugu

    2015-01-01

    Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging), a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI), we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI. PMID:26691722

  3. Semantic Wavelet-Induced Frequency-Tagging (SWIFT) Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas.

    PubMed

    Koenig-Robert, Roger; VanRullen, Rufin; Tsuchiya, Naotsugu

    2015-01-01

    Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging), a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI), we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI. PMID:26691722

  4. Steadily increasing star formation rates in galaxies observed at 3 ≲ z ≲ 5 in the CANDELS/GOODS-S field

    SciTech Connect

    Lee, Seong-Kook; Ferguson, Henry C.; Dahlen, Tomas; Somerville, Rachel S.; Giavalisco, Mauro; Wiklind, Tommy

    2014-03-10

    We investigate the star formation histories (SFHs) of high redshift (3 ≲ z ≲ 5) star-forming galaxies selected based on their rest-frame ultraviolet (UV) colors in the CANDELS/GOODS-S field. By comparing the results from the spectral-energy-distribution-fitting analysis with two different assumptions about the SFHs—i.e., exponentially declining SFHs as well as increasing ones, we conclude that the SFHs of high-redshift star-forming galaxies increase with time rather than exponentially decline. We also examine the correlations between the star formation rates (SFRs) and the stellar masses. When the galaxies are fit with rising SFRs, we find that the trend seen in the data qualitatively matches the expectations from a semi-analytic model of galaxy formation. The mean specific SFR is shown to increase with redshift, also in agreement with the theoretical prediction. From the derived tight correlation between stellar masses and SFRs, we derive the mean SFH of star-forming galaxies in the redshift range of 3 ≤ z ≤ 5, which shows a steep power-law (with power α = 5.85) increase with time. We also investigate the formation timescales and mean stellar population ages of these star-forming galaxies. Our analysis reveals that UV-selected star-forming galaxies have a broad range of the formation redshift. The derived stellar masses and the stellar population ages show positive correlation in a sense that more massive galaxies are on average older, but with significant scatter. This large scatter implies that the galaxies' mass is not the only factor which affects the growth or star formation of high-redshift galaxies.

  5. Long-term monthly statistics of mid-latitudinal NmF2 in the Northern geographic hemisphere during geomagnetically quiet and steadily low solar activity conditions

    NASA Astrophysics Data System (ADS)

    Pavlov, Anatoli; Pavlova, Nadezhda

    2016-07-01

    Long-term mid-latitude hourly values of NmF2 measured in 1957-2015 by 10 ionosondes (Point Arguello, Wallops Is., Boulder, de l'Ebre, Rome, Ottawa, Pruhonice, Dourbes, Slough, and Juliusruh) in the Northern geographic hemisphere were processed to select periods of geomagnetically quiet and low solar activity conditions to calculate several descriptive statistics of the noon NmF2 for each month, including the mathematical expectation, most probable value, arithmetic average, and arithmetic average median. The month-to-month variability of these descriptors allowed us to identify months of a year when they reach their extremes (maxima, minima). The calculated month-to-month variations of the NmF2 statistical parameters made it possible to study the winter anomaly and spring-autumn asymmetry in these statistical parameters.

  6. Long-term monthly statistics of mid-latitudinal NmF2 in the northern geographic hemisphere during geomagnetically quiet and steadily low solar activity conditions

    NASA Astrophysics Data System (ADS)

    Pavlov, A. V.; Pavlova, N. M.

    2016-05-01

    Long-term mid-latitude hourly values of NmF2 measured in 1957-2015 by 10 ionosondes in the Northern geographic hemisphere were processed to select periods of geomagnetically quiet and low solar activity conditions to calculate several descriptive statistics of the noon NmF2 for each month, including the mathematical expectation, most probable value, arithmetic average, and arithmetic average median. The month-to-month variability of these descriptors allowed us to identify months of a year when they reach their extremes (maxima, minima). The calculated month-to-month variations of the NmF2 statistical parameters made it possible to study the winter anomaly and spring-autumn asymmetry in these statistical parameters.

  7. Jet flow in steadily swimming adult squid.

    PubMed

    Anderson, Erik J; Grosenbaugh, Mark A

    2005-03-01

    important than L/D to predict jet structure. Average jet velocities in steadily swimming squid ranged from 19.9 to 85.8 cm s(-1) (0.90-2.98 L(m) s(-1)) and were always greater in magnitude than swimming speed. Maximum instantaneous fluid speeds within squid jets ranged from 25.6 to 136.4 cm s(-1). Average jet thrust determined both from jet velocity and from three-dimensional approximations of momentum change in successive jet visualizations showed some differences and ranged from 0.009 to 0.045 N over the range of swimming speeds observed. The fraction by which the average jet velocity exceeded the swimming speed, or 'slip', decreased with increasing swimming speed, which reveals higher jet propulsive efficiency at higher swimming speeds. Jet angle, subtended from the horizontal, decreased from approximately 29 degrees to 7 degrees with increasing swimming speed. Jet frequency ranged from 0.6 to 1.3 Hz in the majority of swimming sequences, and the data suggest higher frequencies at the lowest and highest speeds. Jet velocity, angle, period and frequency exhibited increased variability at speeds between 0.6 and 1.4 L(m) s(-1). This suggests that at medium speeds squid enjoy an increased flexibility in the locomotive strategies they use to control their dynamic balance. PMID:15767313

  8. 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.

  9. Long-term monthly statistics of the mid-latitude ionospheric E-layer peak electron density in the Northern geographic hemisphere during geomagnetically quiet and steadily low solar activity conditions

    NASA Astrophysics Data System (ADS)

    Pavlov, Anatoli; Pavlova, Nadezhda

    2016-07-01

    Long-term hourly values of the ionospheric E-layer peak electron density, NmE, measured during the time period of 1957-2014 by 4 mid-latitude ionosondes (Wallops Island, Boulder, de l'Ebre, and Rome) in the Northern geographic hemisphere were processed to select periods of geomagnetically quiet and low solar activity conditions to calculate several descriptive statistics of NmE close to noon for each month in a year, including the mathematical expectation of NmE, the standard deviations of NmE from the mathematically expected NmE, and the NmE variation coefficient. The month-to-month variability of these descriptors allowed us to identify months of a year when they reach their extremes (maxima, minima). We found that the most probable NmE cannot be considered as the best statistical parameter among the most probable NmE and the mathematically expected NmE in statistical studies of month-to-month variations of NmE. Depending on a choice of an ionosonde and a month, the calculated NmE variation coefficient changes from 5 to 12 %.

  10. 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…

  11. Strategies to Increase Physical Activity

    PubMed Central

    Tuso, Phillip

    2015-01-01

    The benefits of physical activity are well known and well publicized. Healthy People 2020 has determined that physical activity is one of their key interventions to improve health in America. Despite wide acceptance that physical activity is a low-cost alternative to disease treatment and prevention, most Americans still do not exercise the recommended minimum of 150 minutes per week. Underpinning such recommendations is the growing concern that unless we change our behavior around active living, health care costs to treat preventable disease will become unsustainable and have a substantial impact on the financial health of the US. For this reason, physicians, health care executives, and community leaders are working together to improve total health for all Americans. One key intervention to prevent preventable diseases and to make health care more affordable is to increase the percentage of Americans who are physically active. No single intervention will increase activity rates, but a group of interventions working together in synergy may be the stimulus needed to get Americans moving. The five strategies discussed in this paper include 1) measure physical activity as a vital sign; 2) encourage patients to be physically active at least 150 minutes per week; 3) create healthy environments by making it easier for patients to be physically active where they live, learn, work, play, and pray; 4) monitor disease incidence of patients who are physically active vs those who are not physically active; and 5) spread best practices. PMID:26517440

  12. Upper atmosphere has cooled steadily for three decades

    NASA Astrophysics Data System (ADS)

    Wendel, JoAnna

    2014-11-01

    Increasing amounts of greenhouse gases released by human activities do not just affect only the lower atmosphere: Scientists project that anthropogenic carbon emissions have caused a cooling trend in the upper atmosphere, between 200 and 400 kilometers, over the past few decades. Cooling in this atmospheric region can affect the operations of satellites and the orbits of space junk. However, data about cooling trends in the upper atmosphere are still incomplete, and better data are needed to confirm this projection.

  13. 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.

  14. 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…

  15. 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.

  16. 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

  17. 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.

  18. Increased flexibility decreases antifreeze protein activity

    PubMed Central

    Patel, Shruti N; Graether, Steffen P

    2010-01-01

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

  19. The effect of self-induced electric field on Langmuir turbulence formed by a steadily injected electron beam

    NASA Astrophysics Data System (ADS)

    Zharkova, Valentina; Siversky, Taras

    We investigated the stability of a steadily injected electron beam with lower energy knee and its interaction with the ambient plasma via a generation of Langmuir turbulence at various depths of flaring atmospheres. The solutions are sought of simultaneous Fokker-Planck and wave diffusion equations for the atmospheres being a result of hydrodynamic response to electron beam injection. We identify a few time and length scales of the increased Langmuir turbulence and the effect of self-induced electric field on the level of this turbulence at different atmospheric levels.

  20. Physical activity increases bone mass during growth

    PubMed Central

    Karlsson, Magnus K.; Nordqvist, Anders; Karlsson, Caroline

    2008-01-01

    Background The incidence of fragility fractures has increased during the last half of the 1990′s. One important determinant of fractures is the bone mineral content (BMC) or bone mineral density (BMD), the amount of mineralised bone. If we could increase peak bone mass (the highest value of BMC reached during life) and/or decrease the age-related bone loss, we could possibly improve the skeletal resistance to fracture. Objective This review evaluates the importance of exercise as a strategy to improve peak bone mass, including some aspects of nutrition. Design Publications within the field were searched through Medline (PubMed) using the search words: exercise, physical activity, bone mass, bone mineral content, bone mineral density, BMC, BMD, skeletal structure and nutrition. We included studies dealing with exercise during growth and young adolescence. We preferably based our inferences on randomised controlled trials (RCT), which provide the highest level of evidence. Results Exercise during growth increases peak bone mass. Moderate intensity exercise intervention programs are beneficial for the skeletal development during growth. Adequate nutrition must accompany the exercise to achieve the most beneficial skeletal effects by exercise. Conclusion Exercise during growth seems to enhance the building of a stronger skeleton through a higher peak bone mass and a larger bone size. PMID:19109652

  1. 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…

  2. Increasing Physical Activity in Individuals with Autism

    ERIC Educational Resources Information Center

    Todd, Teri; Reid, Greg

    2006-01-01

    This study investigated the outcomes of an intervention package on participation in two physical activities: snowshoeing and walking/jogging. Three male secondary school students who had been diagnosed with autism and were attending a school for students with intellectual disabilities participated in a 6-month outdoor physical activity program.…

  3. Semiempirical method for prediction of aerodynamic forces and moments on a steadily spinning light airplane

    NASA Technical Reports Server (NTRS)

    Pamadi, Bandu N.; Taylor, Lawrence W., Jr.

    1987-01-01

    A semi-empirical method is presented for the estimation of aerodynamic forces and moments acting on a steadily spinning (rotating) light airplane. The airplane is divided into wing, body, and tail surfaces. The effect of power is ignored. The strip theory is employed for each component of the spinning airplane to determine its contribution to the total aerodynamic coefficients. Then, increments to some of the coefficients which account for centrifugal effect are estimated. The results are compared to spin tunnel rotary balance test data.

  4. 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…

  5. 43 CFR 4110.3-1 - Increasing active use.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Increasing active use. 4110.3-1 Section... Qualifications and Preference § 4110.3-1 Increasing active use. When monitoring or documented field observations... forage is available, in proportion to their active use; and (2) To other qualified applicants...

  6. 43 CFR 4110.3-1 - Increasing active use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Increasing active use. 4110.3-1 Section... Qualifications and Preference § 4110.3-1 Increasing active use. When monitoring or documented field observations... forage is available, in proportion to their active use; and (2) To other qualified applicants...

  7. 43 CFR 4110.3-1 - Increasing active use.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Increasing active use. 4110.3-1 Section... Qualifications and Preference § 4110.3-1 Increasing active use. When monitoring or documented field observations... forage is available, in proportion to their active use; and (2) To other qualified applicants...

  8. 43 CFR 4110.3-1 - Increasing active use.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Increasing active use. 4110.3-1 Section... Qualifications and Preference § 4110.3-1 Increasing active use. When monitoring or documented field observations... forage is available, in proportion to their active use; and (2) To other qualified applicants...

  9. Mathematical modelling study for water uptake of steadily growing plant root

    NASA Astrophysics Data System (ADS)

    Chu, Jiaqing; Jiao, Weiping; Xu, Jianjun

    2008-02-01

    The root system of plant is a vitally important organ for living plant. One of the major functions of the root system is uptaking water and nutrients from the soil. The present paper analyzes the whole process of water uptake from soil by a steadily growing plant with a single slender root. We start from the basic principles of physics and fluid-dynamics, consider the structure characteristics of the water transport channel formed by the tiny xylems tubes inside plant, and establish a simplified coherent mathematical model to describe the water transport in the complete system consisting of soil, individual plant, including root, stem and leaves-atmosphere, on the basis of the plant physiology. Moreover, we resolve the proposed mathematical model for a simple artificial plant model under a variety of conditions, in terms of the numerical approach as well as analytical approach. It is shown that the results obtained by both approaches are in very good agreement; the theoretical predictions are qualitatively consistent with the practical experiences very well. The simplified mathematical model established in the present paper may provide a basis for the further investigations on the more sophisticated mathematical model.

  10. 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…

  11. Technology to promote and increase physical activity in heart failure.

    PubMed

    Franklin, Nina C

    2015-01-01

    Regular physical activity is firmly recommended as part of a multifaceted approach to heart failure (HF) self-management. Unfortunately, research indicates that most patients are less likely to engage in and adhere to such activities. The widespread use of information and communication technology tools and resources offers an innovative and potentially beneficial avenue for increasing physical activity levels in HF patients. This article presents specific ways in which advances in information and communication technologies, including Internet- and mobile-based communications, social media platforms, and self-monitoring health devices, can serve as a means to broadly promote increasing levels of physical activity to improve health outcomes in the HF population.

  12. The recent increase in Atlantic hurricane activity: causes and implications.

    PubMed

    Goldenberg, S B; Landsea, C W; Mestas-Nunez, A M; Gray, W M

    2001-07-20

    The years 1995 to 2000 experienced the highest level of North Atlantic hurricane activity in the reliable record. Compared with the generally low activity of the previous 24 years (1971 to 1994), the past 6 years have seen a doubling of overall activity for the whole basin, a 2.5-fold increase in major hurricanes (>/=50 meters per second), and a fivefold increase in hurricanes affecting the Caribbean. The greater activity results from simultaneous increases in North Atlantic sea-surface temperatures and decreases in vertical wind shear. Because these changes exhibit a multidecadal time scale, the present high level of hurricane activity is likely to persist for an additional approximately 10 to 40 years. The shift in climate calls for a reevaluation of preparedness and mitigation strategies.

  13. 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

  14. 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...

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

    PubMed

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

    2009-11-01

    The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second language. Native English speaking exchange students learning German were examined with functional magnetic resonance imaging while reading words in three different languages at two points in time: at the beginning of their stay (day 1) and 5 months later (day 2), when second language proficiency had significantly increased. On day 1, second language words evoked more frontal activation than words from the mother tongue. These differences were diminished on day 2. We therefore conclude that with increasing second language proficiency, lexico-semantic processing of second language words needs less frontal control. Our results demonstrate that lexico-semantic processing of first and second language converges onto similar networks as second language proficiency increases.

  16. Activation of HIF-1α does not increase intestinal tumorigenesis

    PubMed Central

    Xue, Xiang; Ramakrishnan, Sadeesh K.

    2014-01-01

    The hypoxic response is mediated by two transcription factors, hypoxia-inducible factor (HIF)-1α and HIF-2α. These highly homologous transcription factors are induced in hypoxic foci and regulate cell metabolism, angiogenesis, cell proliferation, and cell survival. HIF-1α and HIF-2α are activated early in cancer progression and are important in several aspects of tumor biology. HIF-1α and HIF-2α have overlapping and distinct functions. In the intestine, activation of HIF-2α increases inflammation and colon carcinogenesis in mouse models. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1α is beneficial and can reduce intestinal inflammation. HIF-1α is a critical transcription factor regulating epithelial barrier function following inflammation. The beneficial value of pharmacological agents that chronically activate HIF-1α is decreased due to the tumorigenic potential of HIFs. The present study tested the hypothesis that chronic activation of HIF-1α may enhance colon tumorigenesis. Two models of colon cancer were assessed, a sporadic and a colitis-associated colon cancer model. Activation of HIF-1α in intestinal epithelial cells does not increase carcinogenesis or progression of colon cancer. Together, the data provide proof of principle that pharmacological activation of HIF-1α could be a safe therapeutic strategy for inflammatory bowel disease. PMID:24875099

  17. 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

  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. 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…

  20. 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…

  1. 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...

  2. Increased Mitochondrial Activity in Anthrax-Induced Cell Death

    PubMed Central

    Li, Chi

    2009-01-01

    Pathogenesis of anthrax lethal toxin (LT) is attributed to its ability to cause death of infected cells. New work has demonstrated that increase of mitochondrial F1F0 ATPase activity and subsequent depletion of cellular ATP level are critical early events during LT-induced cell death. PMID:26124679

  3. 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…

  4. 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

  5. Chromosome 1 replacement increases brain orexins and antidepressive measures without increasing locomotor activity.

    PubMed

    Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Akladious, Afaf; Strohl, Kingman P

    2014-12-01

    Decreased orexin level has been well demonstrated in patients suffering from narcolepsy, depression accompanied with suicide attempt; obstructive sleep apnea and comorbidity were also demonstrated in these diseases. As C57BL/6J (B6) mice are more "depressed" and have lower brain orexins than A/J mice, B6 mice having chromosome 1 replacement (B6A1 mice) might have restored orexin levels and less depressive behavior. We studied the behavior of 4-6 month old B6, A/J and B6A1 mice with forced swim, tail suspension, and locomotor activity tests. The animals were then sacrificed and hypothalamus and medullas dissected from brain tissue. Orexins-A and -B were determined by radioimmunoassay. Compared with A/J mice, B6 mice displayed several signs of depression, including increased immobility, increased locomotors activity, and decreased orexin A and -B levels in both the hypothalamus and medulla. Compared to B6 mice, B6A1 mice exhibited significantly higher levels of orexins-A and -B in both brain regions. B6A1 mice also exhibited antidepressive features in most of measured variables, including decreased locomotor activity, decreased immobility and increased swim in tail suspension test; compared with B6 mice, however. B6A1 mice also reversed immobility in the early phase of the swim test. In summary, B6 mice exhibited depressive attributes compared with A/J mice, including increased locomotor activity, greater immobility, and decreased brain orexins, these were largely reversed in B6A1 mice. We conclude that orexin levels modulate these B6 behaviors, likely due to expression of A/J alleles on Chromosome 1.

  6. Increasing the hydrogenation activity of commercial catalysts for selective hydrocracking

    SciTech Connect

    Khashagul`gova, N.S.; Freiman, L.L.; Zelentsov, Yu.N.

    1994-07-01

    The catalysts generally used in hydrodewaxing or selective hydrocracking of n-paraffins are zeolites with the pentasil structure: TsVK, TsVM, TsVN, and Ultrasil. For use in the production of high-quality transformer oils from paraffinic feedstocks, these catalysts have not only a high cracking activity but also an adequate hydrogenating activity. Catalysts containing a nickel-molybdenum complex (or nickel molybdate synthesized by a specific method) are higher in hydrogenating activity in comparison with catalysts in which the metals are introduced by coextrusion or impregnation. Precipitation of a nickel-molybdenum complex on a solid support (aluminosilicate or zeolite) tends to increase its hydrogenating activity, so that the content of the hydrogenating metals in the catalyst can be reduced. This report describes studies on catalysts based on TsVM and TsVN high-silica zeolites.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Exercising self-control increases relative left frontal cortical activation.

    PubMed

    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion).

  12. 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

  13. Increased hurricane activity during the Early Toarcian extreme warmth

    NASA Astrophysics Data System (ADS)

    Bodin, Stephane; Krencker, Francois-Nicolas; Suan, Guillaume; Heimhofer, Ulrich; Immenhauser, Adrian

    2014-05-01

    Theoretical considerations led to the postulation that hurricane activity should increase on a warming planet. Finding physical proof for this relationship remains, however, a difficult task since no clear trend is yet emerging from records of present-day anthropogenic warming. The geological past offers the opportunity to test this hypothesis by assessing episodes of extreme warming events, such as the Toarcian Oceanic Anoxic Event (T-OAE, Early Jurassic, ca. 180 Ma). The T-OAE is characterized by a rapid 4-5°C global warming likely induced by the massive release of greenhouse gases into the atmosphere as a consequence of the activity of the Karoo-Ferrar large igneous province. Within the western Tethyan realm (Morocco, Portugal, France, England, etc.), a systematic increase in the occurrence of storm-related deposits is observed within the shallow-water sediments deposited during the T-OAE, notably at its onset. Increased tempestite occurrences can be observed in both siliciclastic- and carbonate-dominated environments. In the Moroccan High Atlas, hummocky cross-stratification (HCS) occurs ubiquitous within the T-OAE, but is otherwise rare in this tide-dominated basin. Interestingly, the palaeolatitude of the High Atlas Basin (10°N during the Early Jurassic) rules out winter storms as the driving mechanism behind the formation of the HCS, and suggests therefore a significant increase of tropical hurricane activity associated with the Early Toarcian global warming.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Increased serum thymidine kinase activity in acute sarcoidosis.

    PubMed

    Tajima, Syunji; Sando, Yoshichika; Maeno, Toshitaka; Sagawa, Naoki; Nara, Mami; Maeno, Yuri; Nakagawa, Junichi; Ito, Toshio; Hoshino, Yoichi; Suga, Tatsuo; Arai, Masashi; Kurabayashi, Masahiko

    2002-02-01

    This is the first case report of acute sarcoidosis with increased serum thymidine kinase (TK) activity. A 43-year-old male presented fever, swelling of parotid glands, lymphadenopathy, and peripheral neuropathy. Sarcoidosis was pathologically diagnosed by lung and parotid gland biopsy. His serum TK, which was increased to 11.2 U/l at diagnosis (normal <5 U/l), normalized after glucocorticoid therapy. Serum TK has been considered as a good marker of the proliferative activity of various types of neoplasms. Its rise in sarcoidosis has, however, not been described. Because acute sarcoidosis sometimes resembles malignant lymphoma, the possible rise of serum TK in sarcoidosis may be worthy of note. PMID:11868600

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. [Increasing activity of a monoamine oxidase by random mutation].

    PubMed

    Chen, Xuejun; Ma, Yuanhui; Shao, Jianhua; Lai, Dunyue; Wang, Zhiguo; Chen, Zhenming

    2014-01-01

    The monoamine oxidase mutant A-1 (F210V/L213C) from Aspergillus niger showed some catalytic activity on mexiletine. To futher improve its activity, the mutant was subjected to directed evolution with MegaWHOP PCR (Megaprimer PCR of Whole Plasmid) and selection employing a high-throughput agar plate-based colorimetric screen. This approach led to the identification of a mutant ep-1, which specific activity was 189% of that for A-1. The ep-1 also showed significantly improved enantioselectivity, with the E value increased from 101 to 282; its kinetic k(cat)/K(m) value increased from 0.001 51 mmol/(L x s) to 0.002 89 mmol/(L x s), suggesting that catalytic efficiency of ep-1 had been improved. The mutant showed obviously higher specific activities on 7 of all tested 11 amines substrates, and the others were comparable. Sequence analysis revealed that there was a new mutation T162A on ep-1. The molecular dynamics simulation indicated that T162A may affect the secondary structure of the substrate channel and expand the binding pocket. PMID:24818485

  6. 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.

  7. 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

  8. 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

  9. Increased Rho kinase activity in congestive heart failure

    PubMed Central

    Dong, Ming; Liao, James K.; Fang, Fang; Lee, Alex Pui-Wai; Yan, Bryan Ping-Yen; Liu, Ming; Yu, Cheuk-Man

    2012-01-01

    Aims Rho kinases (ROCKs) are the best characterized effectors of the small G-protein RhoA, and play a role in enhanced vasoconstriction in animal models of congestive heart failure (CHF). This study examined if ROCK activity is increased in CHF and how it is associated with the outcome in CHF. Methods and results Patients admitted with CHF (n =178), disease controls (n =31), and normal subjects (n =30) were studied. Baseline ROCK activity was measured by phosphorylation of themyosin-binding subunit in peripheral leucocytes. The patients were followed up for 14.4 ± 7.2 months (range 0.5–26 months) or until the occurrence of cardiac death. The ROCK activity in CHF patients (2.93 ± 0.87) was significantly higher than that of the disease control (2.06 ± 0.38, P < 0.001) and normal control (1.57 ± 0.43, P < 0.001) groups. Similarly, protein levels of ROCK1 and ROCK2 as well as the activity of RhoA in CHF were significantly higher than in disease controls and normal controls (all P < 0.05). Dyspnoea at rest (β =0.338, P < 0.001), low left ventricular ejection fraction (β = –0.277, P < 0.001), and high creatinine (β =0.202, P =0.006) were independent predictors of the baseline ROCK activity in CHF. Forty-five patients died within 2 years follow-up (25.3%). Combining ROCK activity and N-terminal pro brain natriuretic peptide (NT-proBNP) had an incremental value (log rank χ2 =11.62) in predicting long-term mortality when compared with only NT-proBNP (log rank χ2 =5.16, P < 0.05). Conclusion ROCK activity is increased in CHF and it might be associated with the mortality in CHF. ROCK activity might be a complementary biomarker to CHF risk stratification. PMID:22588320

  10. 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.

  11. Both novelty and expertise increase action observation network activity.

    PubMed

    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.

  12. 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

  13. 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.

  14. Prostate cancer and the increasing role of active surveillance.

    PubMed

    Alonzo, David Gabriel; Mure, Amanda Lynne; Soloway, Mark S

    2013-09-01

    Prostate cancer (PC) is the most often diagnosed non-skin cancer and the second leading cause of cancer-related death among men in the United States. As a result, for many years the American Urological Association (AUA) and the American Cancer Society have issued statements recommending screening for PC, resulting in its widespread implementation in the United States. Recently, the United States Preventative Services Task Force gave PC screening a recommendation of D, that is, against PC screening for all men. The AUA countered this recommendation, stating that since the development of PC screening using prostate-specific antigen, a reduction in PC-specific mortality has been seen, and that the risk reduction occurred in a setting in which many of the patients were not aggressively treated for prostate cancer. Active surveillance may be described as a method to potentially delay or obviate the need for treatment in men with clinically insignificant PC or PC thought to be at low risk for progression. Studies have shown no significant difference in outcome or pathology between men with low risk PC who receive treatment at the point of progression and those undergoing immediate treatment. Ongoing studies are evaluating the efficacy and utility of active surveillance for low-risk PC. Interim results of these studies have shown that approximately 30% of patients progress on active surveillance. However, "progression" does not necessarily mean treatment failure; rarely do patients develop locally advanced or metastatic disease. Active surveillance has also been shown to be cost-effective when compared with immediate treatment for PC. Longer follow-up may continue to show an increased benefit of active surveillance as a reasonable initial approach to the management of men with low-risk, clinically localized PC.

  15. Rise of a variable-viscosity fluid in a steadily spreading wedge-shaped conduit with accreting walls

    USGS Publications Warehouse

    Lachenbruch, Arthur H.; Nathenson, Manuel

    1976-01-01

    Relatively rigid plates making up the outer 50 to 100 km of the Earth are steadily separating from one another along narrow globe-circling zones of submarine volcanism, the oceanic spreading centers. Continuity requires that the viscous underlying material rise beneath spreading centers and accrete onto the steadily diverging plates. It is likely that during the rise the viscosity changes systematically and that the viscous tractions exerted on the plates contribute to the unique pattern of submarine mountains and earthquake faults observed at spreading centers. The process is modeled by viscous creep in a wedge-shaped conduit (with apex at the sea floor) in which the viscosity varies as rm where r is distance from the apex and m is a parameter. For these conditions, the governing differential equations take a simple form. The solution for the velocity is independent of r and of the sign of m. As viscous stresses vary as rm-1, the pattern of stress on the conduit wall is sensitive to viscosity variation. For negative m, the viscous pressure along the base of the conduit is quite uniform; for positive m, it falls toward zero in the axial region as the conduit base widens. For small opening angles, viscous forces push the plates apart, and for large ones, they oppose plate separation. Though highly idealized, the solution provides a tool for investigating tectonic processes at spreading centers.

  16. 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

  17. Prescribed active learning increases performance in introductory biology.

    PubMed

    Freeman, Scott; 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.

  18. Ethynylestradiol increases expression and activity of rat liver MRP3.

    PubMed

    Ruiz, María L; Villanueva, Silvina S M; Luquita, Marcelo G; Vore, Mary; Mottino, Aldo D; Catania, Viviana A

    2006-06-01

    We evaluated the effect of ethynylestradiol (EE) administration (5 mg/kg b.wt. s.c., for 5 consecutive days) on the expression and activity of multidrug resistance-associated protein 3 (Mrp3) in rats. Western blotting analysis revealed decreased Mrp2 (-41%) and increased Mrp3 (+200%) expression by EE. To determine the functional impact of up-regulation of Mrp3 versus Mrp2, we measured the excretion of acetaminophen glucuronide (APAP-glu), a common substrate for both transporters, into bile and perfusate in the recirculating isolated perfused liver (IPL) model. APAP-glu was generated endogenously from acetaminophen (APAP), which was administered as a tracer dose (2 micromol/ml) into the perfusate. Biliary excretion of APAP-glu after 60 min of perfusion was reduced in EE-treated rats (-80%). In contrast, excretion into the perfusate was increased by EE (+45%). Liver content of APAP-glu at the end of the experiment was reduced by 36% in the EE group. The total amount of glucuronide remained the same in both groups. Taken together, these results indicate that up-regulation of Mrp3 led to an exacerbated basolateral versus canalicular excretion of conjugated APAP in IPL. We conclude that induced expression of basolateral Mrp3 by EE may represent a compensatory mechanism to prevent intracellular accumulation of common Mrp substrates, either endogenous or exogenous, due to reduced expression and activity of apical Mrp2. PMID:16554369

  19. The Potential for Pocket Parks to Increase Physical Activity

    PubMed Central

    Cohen, Deborah A.; Marsh, Terry; Williamson, Stephanie; Han, Bing; Derose, Kathryn Pitkin; Golinelli, Daniella; McKenzie, Thomas L.

    2014-01-01

    Purpose To assess the use of new pocket parks in low-income neighborhoods. Setting Los Angeles Subjects Parks users and residents living within ½ mile of 3 pocket parks and 15 neighborhood parks Intervention The creation of pocket parks Design Quasi-experimental post-only comparison Measures We used the System of Observing Play and Recreation in Communities (SOPARC) to measure park use and park-based physical activity and surveyed park users and residents about their park use. Analysis We surveyed 392 and 432 household members within one-half mile of the 3 pocket parks before and after park construction, respectively, as well as 71 pocket park users and compared them to 992 neighborhood park users and 342 residents living within ½ mile of other neighborhood parks. We compared pocket park use to playground area use in the larger neighborhood parks. We used descriptive statistics and Generalized Estimating Equations for the analysis. Results Overall, pocket park use compared favorably in promoting moderate-to-vigorous physical activity with that of existing playground space in nearby parks and they were cost-effective at $0.73/MET hour gained. Pocket park visitors walked an average of 0.25 miles to get there. Conclusions Pocket parks, when perceived as attractive and safe destinations, may increase physical activity by encouraging families with children to walk there. Additional strategies and programs may be needed to encourage more residents to use the parks. PMID:24380461

  20. Use of active video games to increase physical activity in children: a (virtual) reality?

    PubMed

    Foley, Louise; Maddison, Ralph

    2010-02-01

    There has been increased research interest in the use of active video games (in which players physically interact with images onscreen) as a means to promote physical activity in children. The aim of this review was to assess active video games as a means of increasing energy expenditure and physical activity behavior in children. Studies were obtained from computerized searches of multiple electronic bibliographic databases. The last search was conducted in December 2008. Eleven studies focused on the quantification of the energy cost associated with playing active video games, and eight studies focused on the utility of active video games as an intervention to increase physical activity in children. Compared with traditional nonactive video games, active video games elicited greater energy expenditure, which was similar in intensity to mild to moderate intensity physical activity. The intervention studies indicate that active video games may have the potential to increase free-living physical activity and improve body composition in children; however, methodological limitations prevent definitive conclusions. Future research should focus on larger, methodologically sound intervention trials to provide definitive answers as to whether this technology is effective in promoting long-term physical activity in children.

  1. Increased parietal activity after training of interference control.

    PubMed

    Oelhafen, Stephan; Nikolaidis, Aki; Padovani, Tullia; Blaser, Daniela; Koenig, Thomas; Perrig, Walter J

    2013-11-01

    Recent studies suggest that computerized cognitive training leads to improved performance in related but untrained tasks (i.e. transfer effects). However, most study designs prevent disentangling which of the task components are necessary for transfer. In the current study, we examined whether training on two variants of the adaptive dual n-back task would affect untrained task performance and the corresponding electrophysiological event-related potentials (ERPs). Forty three healthy young adults were trained for three weeks with a high or low interference training variant of the dual n-back task, or they were assigned to a passive control group. While n-back training with high interference led to partial improvements in the Attention Network Test (ANT), we did not find transfer to measures of working memory and fluid intelligence. ERP analysis in the n-back task and the ANT indicated overlapping processes in the P3 time range. Moreover, in the ANT, we detected increased parietal activity for the interference training group alone. In contrast, we did not find electrophysiological differences between the low interference training and the control group. These findings suggest that training on an interference control task leads to higher electrophysiological activity in the parietal cortex, which may be related to improvements in processing speed, attentional control, or both.

  2. Writer's cramp: increased dorsal premotor activity during intended writing.

    PubMed

    Delnooz, Cathérine C S; Helmich, Rick C; Medendorp, W P; Van de Warrenburg, Bart P C; Toni, Ivan

    2013-03-01

    Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing.

  3. Increased microglial catalase activity in multiple sclerosis grey matter.

    PubMed

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.

  4. 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

  5. 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.

  6. Wnt Pathway Activation Increases Hypoxia Tolerance during Development

    PubMed Central

    Gersten, Merril; Zhou, Dan; Azad, Priti; Haddad, Gabriel G.; Subramaniam, Shankar

    2014-01-01

    Adaptation to hypoxia, defined as a condition of inadequate oxygen supply, has enabled humans to successfully colonize high altitude regions. The mechanisms attempted by organisms to cope with short-term hypoxia include increased ATP production via anaerobic respiration and stabilization of Hypoxia Inducible Factor 1α (HIF-1α). However, less is known about the means through which populations adapt to chronic hypoxia during the process of development within a life time or over generations. Here we show that signaling via the highly conserved Wnt pathway impacts the ability of Drosophila melanogaster to complete its life cycle under hypoxia. We identify this pathway through analyses of genome sequencing and gene expression of a Drosophila melanogaster population adapted over >180 generations to tolerate a concentration of 3.5–4% O2 in air. We then show that genetic activation of the Wnt canonical pathway leads to increased rates of adult eclosion in low O2. Our results indicate that a previously unsuspected major developmental pathway, Wnt, plays a significant role in hypoxia tolerance. PMID:25093834

  7. 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

  8. Effect of Increasing the Choice of Active Options on Children’s Physical Activity

    PubMed Central

    Feda, Denise M.; Lambiase, Maya J.; McCarthy, Thomas F.; Barkley, Jacob E.; Roemmich, James. N.

    2012-01-01

    Objectives To determine whether increasing the choice of physical activity options increases the duration and intensity of children’s physically active play. Design This cross-sectional laboratory study included gender (male, female) and choice group [single toy (no choice), three toys (low choice), five toys (high choice)] as between participant factors. Methods Boys and girls (n = 36, 8–12 y) were stratified, randomly assigned to a choice group that always provided access to each participant’s most liked active toy(s), and allowed 60 min of free time. The same sedentary alternatives were freely available to all participants. Physical activity outcomes were measured by accelerometry, heart rate, and direct observation. Results The number of active toys the children played with increased (p < 0.001) across each choice group. Minutes spent in MPA were greater in the low choice (p < 0.05) and high choice (p < 0.02) groups than the no choice group. Active play time was greater (p < 0.01) in the low choice (79%) and high choice (95%) groups compared to the no choice group. Girls in the low and high choice groups had greater (p < 0.05) percent heart rate reserve when compared to girls in the no choice group. There was no difference in the boys’ percent heart rate reserve between the no choice, low choice and high choice groups. Conclusions Increasing the choice of active toys increases both the duration and intensity of physically active play, especially in girls. PMID:22342111

  9. Fluid Shear Stress Increases Neutrophil Activation via Platelet-Activating Factor

    PubMed Central

    Mitchell, Michael J.; Lin, Kimberly S.; King, Michael R.

    2014-01-01

    Leukocyte exposure to hemodynamic shear forces is critical for physiological functions including initial adhesion to the endothelium, the formation of pseudopods, and migration into tissues. G-protein coupled receptors on neutrophils, which bind to chemoattractants and play a role in neutrophil chemotaxis, have been implicated as fluid shear stress sensors that control neutrophil activation. Recently, exposure to physiological fluid shear stresses observed in the microvasculature was shown to reduce neutrophil activation in the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine. Here, however, human neutrophil preexposure to uniform shear stress (0.1–2.75 dyn/cm2) in a cone-and-plate viscometer for 1–120 min was shown to increase, rather than decrease, neutrophil activation in the presence of platelet activating factor (PAF). Fluid shear stress exposure increased PAF-induced neutrophil activation in terms of L-selectin shedding, αMβ2 integrin activation, and morphological changes. Neutrophil activation via PAF was found to correlate with fluid shear stress exposure, as neutrophil activation increased in a shear stress magnitude- and time-dependent manner. These results indicate that fluid shear stress exposure increases neutrophil activation by PAF, and, taken together with previous observations, differentially controls how neutrophils respond to chemoattractants. PMID:24853753

  10. 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.

  11. Altered behavior in spotted hyenas associated with increased human activity

    USGS Publications Warehouse

    Boydston, Erin E.; Kapheim, Karen M.; Watts, Heather E.; Szykman, Micaela; Holekamp, Kay 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.

  12. 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.

  13. Platelet-activating factor-induced increases in glucose kinetics

    SciTech Connect

    Lang, C.H.; Dobrescu, C.; Hargrove, D.M.; Bagby, G.J.; Spitzer, J.J. )

    1988-02-01

    Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose before and for 4 h after either a bolus injection or a constant infusion of PAF. The bolus injection of PAF elevated the rate of glucose appearance (R{sub a}; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose and glucose R{sub a} throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. Because the constant infusion of PAF did stimulate many of the hemodynamic and metabolic alterations produced by endotoxin, this study provides additional support for the potential importance of PAF as a mediator of the early hemodynamic and metabolic sequela of endotoxin shock. Furthermore, the PAF-induced changes in glucose metabolism appear to be mediated by the resultant elevation in plasma catecholamines.

  14. 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.

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

    PubMed Central

    Park, J; Cartwright, C A

    1995-01-01

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

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

    PubMed

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

    2011-03-01

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

  17. Hydrostatic Pressure Increases the Catalytic Activity of Amyloid Fibril Enzymes.

    PubMed

    Luong, Trung Quan; Erwin, Nelli; Neumann, Matthias; Schmidt, Andreas; Loos, Cornelia; Schmidt, Volker; Fändrich, Marcus; Winter, Roland

    2016-09-26

    We studied the combined effects of pressure (0.1-200 MPa) and temperature (22, 30, and 38 °C) on the catalytic activity of designed amyloid fibrils using a high-pressure stopped-flow system with rapid UV/Vis absorption detection. Complementary FT-IR spectroscopic data revealed a remarkably high pressure and temperature stability of the fibrillar systems. High pressure enhances the esterase activity as a consequence of a negative activation volume at all temperatures (about -14 cm(3)  mol(-1) ). The enhancement is sustained in the whole temperature range covered, which allows a further acceleration of the enzymatic activity at high temperatures (activation energy 45-60 kJ mol(-1) ). Our data reveal the great potential of using both pressure and temperature modulation to optimize the enzyme efficiency of catalytic amyloid fibrils.

  18. 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

  19. Hydrostatic Pressure Increases the Catalytic Activity of Amyloid Fibril Enzymes.

    PubMed

    Luong, Trung Quan; Erwin, Nelli; Neumann, Matthias; Schmidt, Andreas; Loos, Cornelia; Schmidt, Volker; Fändrich, Marcus; Winter, Roland

    2016-09-26

    We studied the combined effects of pressure (0.1-200 MPa) and temperature (22, 30, and 38 °C) on the catalytic activity of designed amyloid fibrils using a high-pressure stopped-flow system with rapid UV/Vis absorption detection. Complementary FT-IR spectroscopic data revealed a remarkably high pressure and temperature stability of the fibrillar systems. High pressure enhances the esterase activity as a consequence of a negative activation volume at all temperatures (about -14 cm(3)  mol(-1) ). The enhancement is sustained in the whole temperature range covered, which allows a further acceleration of the enzymatic activity at high temperatures (activation energy 45-60 kJ mol(-1) ). Our data reveal the great potential of using both pressure and temperature modulation to optimize the enzyme efficiency of catalytic amyloid fibrils. PMID:27573584

  20. Proteinase-activated receptors induce nonoxidative, antimicrobial peptides and increased antimicrobial activity in human mononuclear phagocytes.

    PubMed

    Lippuner, Nadine; Morell, Bernhard; Schaffner, Andreas; Schaer, Dominik J

    2007-02-01

    As thrombin and SFLLRNPNDKYEPF (SFLLRN-14), a synthetic ligand, mainly of the proteinase-activated receptor-1 (PAR-1), induce in monocytes the synthesis and secretion of chemokines, the PAR pathway can be viewed as a mononuclear phagocyte-activating principle. Classically, antimicrobial activity of mononuclear phagocytes is the measure for activation. Here, we investigated whether thrombin or SFLLRN-14 increases the antimicrobial activity of human monocytes and compared these effects to those of IFN-gamma. Furthermore, we measured the effects of these agents on the secretion of reactive oxygen intermediates and the antimicrobial activity of acid peptide extracts from monocytes. Human monocytes were exposed to maximally active concentrations of thrombin, SFLLRN-14, and IFN-gamma. Human monocytes treated with thrombin or SFLLRN-14 and then challenged with Salmonella enterica serovar typhimurium, including its attenuated mutant phoP, or Listeria monocytogenes killed, within 3 h, significantly more bacteria than control cells, an effect comparable with or surpassing the effect of IFN-gamma. This finding establishes the proteinase-PAR pathway as a potent, alternate activation pathway of mononuclear phagocytes. Thrombin and SFLLRN-14 had no significant effects on the amount of H(2)O(2) secreted by monocytes. This was in contrast to IFN-gamma, which as expected, increased the secretion of H(2)O(2) by approximately fourfold. Thrombin and SFLLRN-14, but not IFN-gamma, however, significantly increased the antimicrobial activity of acid peptide extracts of monocytes in a radial diffusion assay. Taken together, these findings suggest that IFN-gamma and thrombin differentially regulate oxidative and nonoxidative killing systems of human monocytes. PMID:17095611

  1. ROFA INCREASES CASPASE-3 ACTIVITY IN HUMAN ALVEOLAR MACRAPHAGE

    EPA Science Inventory

    Exposure to air pollution particles produces pulmonary inflammation and injury, but the mechanisms of this injury are unclear. Apoptosis, involving activation of caspases, may be one potential mechanism. In this study, we hypothesized that ROFA, a constituent of air pollution...

  2. Smoking further increases platelet activity in patients with mild hypertension.

    PubMed

    Gleerup, G; Winther, K

    1996-01-01

    In this study the authors examine whether smoking further heightens platelet activity and reduces fibrinolysis above that already present in mild hypertension. Ten smokers and 11 non-smokers, all with mild hypertension (defined as a diastolic pressure between 90 and 110 mm Hg) were compared for their platelet activity in vitro and in vivo and for their fibrinolytic activity. Successive measurements were made with the patients lying at rest after they had assumed the erect posture for 10 min and at the end of a 5-min moderately strenuous exercise test. The threshold for platelet aggregation by ADP in vitro was significantly lower in samples taken from the smokers at rest (1.4 +/- 0.9 mumol L(-1)) than in the non-smokers (3.5 +/- 2.5 mumol L(-1)), and the difference persisted both in the upright posture and after exercise. The level of platelet release of beta-thromboglobulin was, likewise, higher in the smokers in the upright posture. Neither standing up nor physical exercise had any significant influence on either of these two indices of platelet activity. The euglobulin clot lysis time was slightly longer in the smokers than in the non-smokers in all three experimental situations, but the differences were not significant. Inhibitor of tissue plasminogen activator was not materially different in the two groups (Table 2). The results indicate that smoking adds a further element of heightened platelet activity to that inherently present in hypertension.

  3. State Legislation Related to Increasing Physical Activity: 2006-2012

    PubMed Central

    Eyler, Amy A.; Budd, Elizabeth; Camberos, Gabriela J.; Yan, Yan; Brownson, Ross C.

    2016-01-01

    Background Strategies to improve physical activity prevalence often include policy and environmental changes. State-level policies can be influential in supporting access and opportunities for physical activity in schools and communities. The purpose of this study was to explore the prevalence of state legislation related to physical activity and identify the correlates of enactment of this legislation. Methods An online legislative database was used to collect bills from 50 states in the U.S. from 2006-2012 for ten topics related to physical activity. Bills were coded for content and compiled into a database with state-level variables (e.g., obesity prevalence). With enactment status as the outcome, bivariate and multivariate analyses were conducted. Results Of the 1542 bills related to physical activity introduced, 30% (N=460) were enacted. Bills on public transportation and trails were more likely to be enacted than those without these topics. Primary sponsorship by the Republican Party, bipartisan sponsorship, and mention of specific funding amounts were also correlates of enactment. Conclusion Policy surveillance of bills and correlates of enactment are important for understanding patterns in legislative support for physical activity. This information can be used to prioritize advocacy efforts and identify ways for research to better inform policy. PMID:26104603

  4. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

    PubMed

    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.

  5. 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.

  6. 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…

  7. 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...

  8. 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…

  9. 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…

  10. 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…

  11. 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...

  12. Diagnostic performance of increased prolidase activity in schizophrenia.

    PubMed

    Güneş, Mehmet; Bulut, Mahmut; Demir, Süleyman; İbiloğlu, Aslıhan Okan; Kaya, Mehmet Cemal; Atlı, Abdullah; Kaplan, İbrahim; Camkurt, Mehmet Akif; Sir, Aytekin

    2016-02-01

    We investigated whether prolidase activity has a diagnostic test value in schizophrenia and assessed the relation between prolidase activity and sociodemographic-clinical characteristics of patients with schizophrenia. Fifty patients with schizophrenia (diagnosed as schizophrenia according to DSM-V criteria) and 50 healthy volunteers were included in this study. Case and control groups had a similar distribution in age, sex, body mass index (BMI), and smoking status. Serum prolidase activity was measured in both groups and was determined to be significantly higher in the patient group (509.706±41.918) compared to the control group (335.4±13.6; t=6.231; p=0.0001). A cut-off point of 392.65U/L prolidase was determined for diagnostic measures from the plotted ROC curve. The area under the ROC curve was 1.000, which was significant (p<0.0001). Higher values were assigned as the disease state. Both positive predictive value (PPV) and negative predictive value (NPV) were 100% at the cut-off point of 392.650U/L. The prolidase levels of the control group were all below the cut-off point. There were no statistically significant differences between the two groups with regard to age, gender, or BMI (p>0.05), and no correlation was found between mean prolidase activity and age of onset of the disease, family history, disease duration, number of hospitalizations, subtypes of schizophrenia, PANSS scores or sub-scores, CGI-S scores, S-A scale scores, and the antipsychotic treatment (p>0.05). The results of this study indicate that serum prolidase activity may be a useful diagnostic test for schizophrenia; however, further studies are needed to verify this.

  13. Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide Y inputs into the paraventricular nucleus in female rats.

    PubMed

    Cassaglia, Priscila A; Shi, Zhigang; Brooks, Virginia L

    2016-07-01

    Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α-MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R. PMID:27122366

  14. Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis.

    PubMed Central

    Odum, N; Morling, N; Platz, P; Hofmann, B; Ryder, L P; Heilmann, C; Pedersen, F K; Nielsen, L P; Friis, J; Svejgaard, A

    1987-01-01

    The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 patients with active juvenile chronic arthritis (JCA), 10 patients with JCA in remission, and 11 age matched, healthy controls. In addition, the distribution of T 'helper/inducer' (CD4+), T 'suppressor/inducer' (CD4+, Leu8+), T 'suppressor/cytotoxic' (CD8+), and 'natural killer' (NK) cells (CD16+) was studied. Twenty patients and six controls were investigated for the capability to stimulate alloreactivated primed lymphocytes. The prevalence of VLA-1 positive, large cells was significantly increased to 5% (median value) in active JCA as compared with JCA in remission (2%, p less than 0.05) and controls (1%, p less than 0.05), whereas no significant difference between JCA in remission and controls was observed. Except for two patients with active JCA, less than 1% IL2 receptor bearing cells were found in patients with JCA and controls. No significant difference in the prevalence and expression of the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA, JCA in remission, and controls. The prevalence of T suppressor/inducer (CD4+,Leu8+) cells was higher in remission JCA (17%) than in active JCA (11%) and controls (10%). This increase, however, did not reach statistical significance. In conclusion, late stage but not early stage T cell activation antigens were increased in patients with active JCA as compared with patients with JCA in remission and control, whereas some patients in remission had an increased prevalence of T suppressor

  15. 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.

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

    PubMed Central

    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

  17. 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.

  18. Digoxin is a selective modifier increasing platinum drug anticancer activity.

    PubMed

    Bogush, T A; Chernov, V Yu; Dudko, E A; Shprakh, Z S; Bogush, E A; Polotsky, B E; Tjulandin, S A; Davydov, M I

    2016-05-01

    Using the model of breast cancer Ehrlich ascites tumor in mice, we showed that a sigle intraperitoneal injection of cardiac glycoside digoxin 1 h before the intraperitoneal injection of cisplatin increased the anticancer effect of the cytostatic drug more than twice when recalculated for the dose. It is assumed that the modifying effect of digoxin is determined by the direct inhibition of glycolysis in tumor cells. Taking into account the design of the study, we consider promising the clinical evaluation of the effectiveness of digoxin as a modifier of cisplatin efficiency in intracavitary therapy of ascites cancers with pleural and abdominal dissenmination. PMID:27417726

  19. Biotin uptake into human peripheral blood mononuclear cells increases early in the cell cycle, increasing carboxylase activities.

    PubMed

    Stanley, J Steven; Mock, Donald M; Griffin, Jacob B; Zempleni, Janos

    2002-07-01

    Cells respond to proliferation with increased accumulation of biotin, suggesting that proliferation enhances biotin demand. Here we determined whether peripheral blood mononuclear cells (PBMC) increase biotin uptake at specific phases of the cell cycle, and whether biotin is utilized to increase biotinylation of carboxylases. Biotin uptake was quantified in human PBMC that were arrested chemically at specific phases of the cell cycle, i.e., biotin uptake increased in the G1 phase of the cycle [658 +/- 574 amol biotin/(10(6) cells x 30 min)] and remained increased during phases S, G2, and M compared with quiescent controls [200 +/- 62 amol biotin/(10(6) cells x 30 min)]. The abundance of the sodium-dependent multivitamin transporter (SMVT, which transports biotin) was similar at all phases of the cell cycle, suggesting that transporters other than SMVT or splicing variants of SMVT may account for the increased biotin uptake observed in proliferating cells. Activities of biotin-dependent 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase were up to two times greater in proliferating PBMC compared with controls. The abundance of mRNA encoding 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase paralleled carboxylase activities, suggesting that PBMC respond to proliferation with increased expression of genes encoding carboxylases. Similarly, expression of the gene encoding holocarboxylase synthetase (which catalyzes binding of biotin to carboxylases) increased in response to proliferation, suggesting that cellular capacity to biotinylate carboxylases was increased. In summary, these findings suggest that PBMC respond to proliferation with increased biotin uptake early in the cell cycle, and that biotin is utilized to increase activities of two of the four biotin-requiring carboxylases.

  20. Circadian behavioral and melatonin rhythms in the European starling under light-dark cycles with steadily changing periods: evidence for close mutual coupling?

    PubMed

    Kumar, Vinod; Van't Hof, Thomas J; Gwinner, Eberhard

    2007-11-01

    In European starlings exposed to constant conditions, circadian rhythms in locomotion and feeding can occasionally exhibit complete dissociation from each other. Whether such occasional dissociation between two behavioral rhythms reflects on the strength of the mutual coupling of their internal oscillators has not been investigated. To examine this, as well as to elucidate the role of melatonin in this system, we simultaneously measured the rhythms of locomotion, feeding and melatonin secretion in starlings exposed to light-dark (LD) cycles of low intensity with steadily changing periods (T). In birds initially entrained to T 24 LD cycles (12L:12D, 10:0.2 lx), beginning on day 15, T was either lengthened to 26.5 h (experiment 1) or shortened to T 21.5 h (experiment 2) by changing the daily dark period 4 min each day. After 18 and 19 cycles of T 26.5 and T 21.5, respectively, birds were released into constant dim light conditions (LL(dim); 0.2 lx) for about 2 weeks. Locomotor and feeding rhythms were continuously recorded. Plasma melatonin levels were measured at three times: in T 24, when T equaled 26 or 22 h and at the end of T 26.5 or T 21.5 exposure. The results show that, contrary to our expectations, the three rhythms were not dissociated. Rather they remained synchronized and changed their phase angle difference with the light zeitgeber concomitantly and at the same rate. The melatonin rhythm stayed in synchrony with the behavioral rhythms and as a consequence, peaked either during day or at night, depending on the phase relationship between the activity rhythm and the zeitgeber cycle.

  1. 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

  2. Increasing discordant antioxidant protein levels and enzymatic activities contribute to increasing redox imbalance observed during human prostate cancer progression

    PubMed Central

    Chaiswing, Luksana; Zhong, Weixiong; Oberley, Terry D.

    2014-01-01

    A metabolomics study demonstrated a decrease in glutathione and an increase in cysteine (Cys) levels in human prostate cancer (PCa) tissues as Gleason scores increased, indicating redox imbalance with PCa progression. These results were extended in the present study by analyzing redox state of the protein thioredoxin 1 (Trx1) and sulfinylation (SO3) of peroxiredoxins (Prxs) (PrxsSO3) in PCa tissues and cell lines. Lysates of paired human PCa tissues with varying degree of aggressiveness and adjacent benign (BN) tissues were used for analysis. Redox western blot analysis of Trx1 demonstrated low levels of reduced and high levels of oxidized Trx1 (functional and non-functional, respectively) in high grade PCa (Gleason scores 4+4 to 4+5) in comparison to intermediate grade PCa (Gleason scores 3+3 to 3+4) or BN tissues. PrxsSO3 were increased in high grade PCa. Oxidized Trx1 and PrxsSO3 are indicators of oxidative stress. To study whether redox imbalance may potentially affect enzyme activities of antioxidant proteins (AP), we determined levels of selected AP in PCa tissues by western blot analysis and found that mitochondrial manganese superoxide dismutase (MnSOD), Prx 3, and Trx1 were increased in high grade PCa tissues when compared with BN tissues. Enzyme activities of MnSOD in high grade PCa tissues were significantly increased but at a lower magnitude when compared with the levels of MnSOD protein (0.5 folds vs. 2 folds increase). Trx1 activity was not changed in high grade PCa tissues despite a large increase in Trx1 protein expression. Further studies demonstrated a significant increase in posttranslational modifications of tyrosine and lysine residues in MnSOD protein and oxidation of Cys at active site (Cys 32 and Cys 35) and regulatory site (Cys 62 and Cys 69) of Trx1 in high grade PCa compared to BN tissues. These discordant changes between protein levels and enzyme activities are consistent with protein inactivation by redox imbalance and

  3. 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…

  4. 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

  5. The World in Words and Pictures: How Graphic Novels Can Help to Increase Reading Comprehension for Students with Hearing Loss

    ERIC Educational Resources Information Center

    White, Britt

    2011-01-01

    The use of graphic novels to engage students has increased steadily in recent years. School librarians and teachers throughout elementary, middle, and secondary schools are integrating graphic novels into English language arts learning and across the curriculum. The growing acceptance of graphic novels in teaching and learning activities is due in…

  6. 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

  7. [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

  8. [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

  9. 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.

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

    PubMed

    Gillooly, James F; 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.

  11. 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…

  12. 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...

  13. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE.

  14. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE. PMID:27651919

  15. 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…

  16. 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.…

  17. 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…

  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. 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…

  20. 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...

  1. Use of a lag differential reinforcement contingency to increase varied selections of classroom activities.

    PubMed

    Cammilleri, Anthony P; Hanley, Gregory P

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  2. Male Adolescents' Reasons for Participating in Physical Activity, Barriers to Participation, and Suggestions for Increasing Participation

    ERIC Educational Resources Information Center

    Allison, Kenneth R.; Dwyer, John J. M.; Goldenberg, Ellie; Fein, Allan; Yoshida, Karen K.; Boutilier, Marie

    2005-01-01

    This study explored male adolescents' reasons for participating in moderate and vigorous physical activity, perceived barriers to moderate and vigorous physical activity, and suggestions as to what can be done to increase participation in physical activity. A total of 26 male 15- and 16-year-old adolescents participated in focus group sessions,…

  3. 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...

  4. 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...

  5. Use of a Lag Differential Reinforcement Contingency to Increase Varied Selections of Classroom Activities

    ERIC Educational Resources Information Center

    Cammilleri, Anthony P.; Hanley, Gregory P.

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

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

    PubMed

    Gleerup, G; Winther, K

    1991-02-01

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

  7. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  8. 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,…

  9. 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

  10. MAP kinase activity increases during mitosis in early sea urchin embryos.

    PubMed

    Philipova, R; Whitaker, M

    1998-09-01

    A MBP kinase activity increases at mitosis during the first two embryonic cell cycles of the sea urchin embryo. The activity profile of the MBP kinase is the same both in whole cell extracts and after immunoprecipitation with an anti-MAP kinase antibody (2199). An in-gel assay of MBP activity also shows the same activity profile. The activity is associated with the 44 kDa protein that cross-reacts with anti-MAP kinase antibodies. The 44 kDa protein shows cross-reactivity to anti-phosphotyrosine and MAP kinase-directed anti-phosphotyrosine/phosphothreonine antibodies at the times that MBP kinase activity is high. The 2199 antibody co-precipitates some histone H1 kinase activity, but the MBP kinase activity cannot be accounted for by histone H1 kinase-dependent phosphorylation of MBP. The MAP kinase 2199 antibody was used to purify the MBP kinase activity. Peptide sequencing after partial digestion shows the protein to be homologous to MAP kinases from other species. These data demonstrate that MAP kinase activation during nuclear division is not confined to meiosis, but also occurs during mitotic cell cycles. MAP kinase activity in immunoprecipitates also increases immediately after fertilization, which in the sea urchin egg occurs at interphase of the cell cycle. Treating unfertilized eggs with the calcium ionophore A23187 stimulates the increase in MAP kinase activity, demonstrating that a calcium signal can activate MAP kinase and suggesting that the activation of MAP kinase at fertilization is due to the fertilization-induced increase in cytoplasmic free calcium concentration. This signalling pathway must differ from the pathway responsible for calcium-induced inactivation of MAP kinase activity that is found in eggs that are fertilized in meiotic metaphase. PMID:9701549

  11. Geomagnetic activity during the previous day is correlated with increased consumption of sucrose during subsequent days: is increased geomagnetic activity aversive?

    PubMed

    Galic, M A; Persinger, M A

    2004-06-01

    In five separate blocks over a period of several months for 33 female rats the amount of geomagnetic activity during the day before ad libitum access to 10% sucrose or water was positively correlated with the volume of sucrose consumed per 24-hr. period. The strength of the correlation (.62 to .77) declined over the subsequent 10 days from between .12 to -.18 and resembled an extinction curve. In a subsequent experiment four rats exposed to 5 nT to 8 nT, 0.5-Hz magnetic fields that ceased for 30 min. once every 4 hr. for 4 days consumed 11% more sucrose than the four rats exposed to no field. We suggest that the initial consumption of 10% sucrose may have been reinforced because it diminished the aversive physiological effects associated with the increased geomagnetic activity. However, over the subsequent days, as geomagnetic activity decreased or habituation occurred, negative reinforcement did not maintain this behavior.

  12. 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.

  13. 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

  14. Do increases in physical activity encourage positive beliefs about further change in the ProActive cohort?

    PubMed

    Hardeman, Wendy; Michie, Susan; Kinmonth, Ann Louise; Sutton, Stephen

    2011-07-01

    Effects of behaviour change on cognitions are rarely examined within the Theory of Planned Behaviour. We tested whether increases in physical activity resulted in more positive beliefs about further change among a cohort of sedentary adults participating in a behavioural intervention trial (ProActive). At baseline, 6 and 12 months, 365 adults completed questionnaires assessing physical activity and cognitions about becoming more active over the coming year. Objective activity was assessed at baseline and 12 months. Participants reporting larger increases in activity were no more positive about making further increases than those reporting less behaviour change (p-values>0.05). Participants with larger increases in objective activity reported weaker perceived control (β=-0.342; p=0.001) and more negative instrumental attitudes (β=-0.230; p=0.017) at 12 months. Participants may have felt that they had changed enough or measures of perceived success may be more sensitive to behaviour change. Alternatively, long measurement intervals may have missed immediate cognitive and affective consequences of behaviour change, or such effects may require participants to consistently self-monitor or receive feedback on performance. Future studies could test the effect of such techniques on physical activity and a wider range of cognitive, affective and physiological consequences, using more frequent measurement intervals. PMID:21500102

  15. Inhibition of phosphatase and tensin homologue (PTEN) in human ovary in vitro results in increased activation of primordial follicles but compromises development of growing follicles.

    PubMed

    McLaughlin, Marie; Kinnell, Hazel L; Anderson, Richard A; Telfer, Evelyn E

    2014-08-01

    In the mammalian ovary a small number of follicles are steadily recruited from the quiescent pool to undergo development. Follicle loss, maintenance and growth are strictly controlled by complex molecular interactions including the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. Stimulation of PI3K promotes phosphorylation of Akt resulting in follicle survival and activation of growth whereas this pathway is suppressed by the actions of the phosphatase and tensin homologue (PTEN). The aim of this study was to determine the effect of dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate (bpV), a reversible inhibitor of PTEN, on the activation, survival and development of human ovarian follicles in vitro. Biopsied ovarian tissue fragments were obtained from 17 women aged 23-46 years and exposed to 1 µM bpV(HOpic) (n = 146) or control medium (n = 128) for 24 h. Media were then replaced with control medium and all tissue incubated for a further 5 days. Ovarian tissue from each treatment group was fixed after the initial 24 h culture period and phosphorylated Akt was quantified by western blotting. After 6 days incubation all tissue fragments were inspected under light microscopy and any secondary follicles ≥100 µm isolated. Isolated follicles were cultured individually in control medium supplemented with 100 ng/ml recombinant human activin A. Tissue fragments without follicles suitable for isolation were fixed and processed for histological and immunohistochemical analysis. During 6 days culture, follicle activation occurred in tissue samples from both treatment groups but with significantly more follicles progressing to the secondary stage of development in the presence of 1 µM bpV(HOpic) compared with control (31 versus 16%; P < 0.05). Increased activation was associated with increased Akt phosphorylation and increased nuclear export of FOXO3. However isolated and cultured follicles that had been exposed to bpV(HOpic) showed

  16. Inhibition of phosphatase and tensin homologue (PTEN) in human ovary in vitro results in increased activation of primordial follicles but compromises development of growing follicles

    PubMed Central

    McLaughlin, Marie; Kinnell, Hazel L.; Anderson, Richard A.; Telfer, Evelyn E.

    2014-01-01

    In the mammalian ovary a small number of follicles are steadily recruited from the quiescent pool to undergo development. Follicle loss, maintenance and growth are strictly controlled by complex molecular interactions including the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. Stimulation of PI3K promotes phosphorylation of Akt resulting in follicle survival and activation of growth whereas this pathway is suppressed by the actions of the phosphatase and tensin homologue (PTEN). The aim of this study was to determine the effect of dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate (bpV), a reversible inhibitor of PTEN, on the activation, survival and development of human ovarian follicles in vitro. Biopsied ovarian tissue fragments were obtained from 17 women aged 23–46 years and exposed to 1 µM bpV(HOpic) (n = 146) or control medium (n = 128) for 24 h. Media were then replaced with control medium and all tissue incubated for a further 5 days. Ovarian tissue from each treatment group was fixed after the initial 24 h culture period and phosphorylated Akt was quantified by western blotting. After 6 days incubation all tissue fragments were inspected under light microscopy and any secondary follicles ≥100 µm isolated. Isolated follicles were cultured individually in control medium supplemented with 100 ng/ml recombinant human activin A. Tissue fragments without follicles suitable for isolation were fixed and processed for histological and immunohistochemical analysis. During 6 days culture, follicle activation occurred in tissue samples from both treatment groups but with significantly more follicles progressing to the secondary stage of development in the presence of 1 µM bpV(HOpic) compared with control (31 versus 16%; P < 0.05). Increased activation was associated with increased Akt phosphorylation and increased nuclear export of FOXO3. However isolated and cultured follicles that had been exposed to bp

  17. Resistance training increases total energy expenditure and free-living physical activity in older adults.

    PubMed

    Hunter, G R; Wetzstein, C J; Fields, D A; Brown, A; Bamman, M M

    2000-09-01

    The purpose of this study was to determine what effects 26 wk of resistance training have on resting energy expenditure (REE), total free-living energy expenditure (TEE), activity-related energy expenditure (AEE), engagement in free-living physical activity as measured by the activity-related time equivalent (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men (n = 8) and women (n = 7). Before and after training, body composition (four-compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE - REE + thermic response to meals), and ARTE (AEE adjusted for energy cost of standard activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly increased, but body weight did not change. REE increased 6.8%, whereas resting RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased significantly, and AEE (30%) approached significance (P = 0.06). The TEE increase remained significant even after adjustment for the energy expenditure of the resistance training. In response to resistance training, TEE increased and RER decreased. The increase in TEE occurred as a result of increases in both REE and physical activity. These results suggest that resistance training may have value in increasing energy expenditure and lipid oxidation rates in older adults, thereby improving their metabolic profiles.

  18. 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

  19. 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

  20. 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

  1. Ginsenoside Rb1 increases insulin sensitivity by activating AMP-activated protein kinase in male rats.

    PubMed

    Shen, Ling; Haas, Michael; Wang, David Q-H; May, Aaron; Lo, Chunmin C; Obici, Silvana; Tso, Patrick; Woods, Stephen C; Liu, Min

    2015-09-01

    Although ginseng has been reported to ameliorate hyperglycemia in animal models and clinical studies, the molecular mechanisms are largely unknown. We previously reported that chronic treatment with ginsenoside Rb1 (Rb1), a major component of ginseng, significantly reduced fasting glucose and improved glucose tolerance in high-fat diet (HFD)-induced obese rats. These effects were greater than those observed in pair-fed rats, suggesting a direct effect of Rb1 on glucose homeostasis, and this possibility was confirmed in the present study. In lean rats fed standard rodent chow, 5-day treatment with Rb1 significantly improved glucose tolerance and enhanced insulin sensitivity. Notably, those effects were not accompanied by reduced food intake or changed body weight. To elucidate the underlying molecular mechanisms, rats fed a HFD for 4 weeks were treated with Rb1 for 5 days. Subsequently, euglycemic-hyperinsulinemic clamp studies found that compared to vehicle, Rb1, while not changing food intake or body weight, significantly increased glucose infusion rate required to maintain euglycemia. Consistent with this, insulin-induced inhibition of hepatic gluconeogenesis was significantly enhanced and hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase gene expression was suppressed. Additionally, glucose uptake was significantly increased in skeletal muscle. While proximal insulin signaling was not changed after Rb1 treatment, increased phosphorylation of TBC1D4, a downstream target of AMPK signaling, appears to be a key part of the mechanism for Rb1-stimulated glucose uptake in skeletal muscle. These findings indicate that Rb1 has multiple effects on glucose homeostasis, and provide strong rationale for further evaluation of its potential therapeutic role. PMID:26359241

  2. Using targeted messaging to increase physical activity in older adults: a review.

    PubMed

    Ostrander, Rachel E; Thompson, Hilaire J; Demiris, George

    2014-09-01

    Physical activity has many benefits for older adults; however, motivating older adults to engage in and maintain optimal levels of physical activity can be challenging for health care providers. A comprehensive literature review was performed to determine whether any evidence-based methods of delivery or particular content for targeted messaging exist that result in actual improvements in physical activity of older adults. Findings of the review demonstrate that messaging directed toward older adults to be physically active resulted in improvements in physical activity up to 1 year. Across studies many different modes of message delivery were shown to be effective. Message content, whether tailored or not, resulted in significant increases in physical activity. There is evidence to support the use of environmentally mediated messaging (i.e., local walking paths) for stronger results. Targeting the client's stage of change, having an activity partner if preferred, and scheduling physical activity also contribute to improved effects.

  3. Increase in multidrug transport activity is associated with oocyte maturation in sea stars.

    PubMed

    Roepke, Troy A; Hamdoun, Amro M; Cherr, Gary N

    2006-12-01

    In this study, we report on the presence of efflux transporter activity before oocyte maturation in sea stars and its upregulation after maturation. This activity is similar to the multidrug resistance (MDR) activity mediated by ATP binding cassette (ABC) efflux transporters. In sea star oocytes the efflux activity, as measured by exclusion of calcein-am, increased two-fold 3 h post-maturation. Experiments using specific and non-specific dyes and inhibitors demonstrated that the increase in transporter activity involves an ABCB protein, P-glycoprotein (P-gp), and an ABCC protein similar to the MDR-associated protein (MRP)-like transporters. Western blots using an antibody directed against mammalian P-gp recognized a 45 kDa protein in sea star oocytes that increased in abundance during maturation. An antibody directed against sea urchin ABCC proteins (MRP) recognized three proteins in immature oocytes and two in mature oocytes. Experiments using inhibitors suggest that translation and microtubule function are both required for post-maturation increases in transporter activity. Immunolabeling revealed translocation of stored ABCB proteins to the plasma cell membrane during maturation, and this translocation coincided with increased transport activity. These MDR transporters serve protective roles in oocytes and eggs, as demonstrated by sensitization of the oocytes to the maturation inhibitor, vinblastine, by MRP and PGP-specific transporter inhibitors.

  4. 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…

  5. 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…

  6. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    PubMed

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats.

  7. 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…

  8. 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…

  9. Angiotensin II increases diacylglycerol in calf adrenal glomerulosa cells by activating de novo phospholipid synthesis

    SciTech Connect

    Foster, R.H.; Farese, R.V. )

    1989-01-01

    Effects of angiotension II (AII) on diacylglycerol (DAG) synthesis were examined in calf adrenal glomerulosa cells. AII provoked rapid increases in ({sup 3}H) glycerol-labeling and content of DAG. Effects on ({sup 3}H) glycerol-labeling of DAG were observed both in cells prelabeled with ({sup 3}H) glycerol for 60 minutes, and when AII and ({sup 3}H) glycerol were added simultaneously. Increases in ({sup 3}H) DAG labeling were associated with increases in total glycerolipid labeling, and in simultaneous addition experiments, were preceded by increased ({sup 3}H) phosphatidic acid (PA) labeling. Labeling of glycerol-3-PO{sub 4}, on the other hand, was not increased by AII, suggesting that increases in lipid labeling were not due to prior increases in precursor specific activity. ACTH, which were not increase precursor specific activity. ACTH, which does not increase the hydrolysis of inositol-phospholipids appreciably in this tissue, provoked increases in content and ({sup 3}H) glycerol-labeling of DAG, which were only slightly less than those provoked by AII. Thus, part of the AII-induced increase in DAG may also be derived from sources other than inositol-phospholipids. Moreover, AII-induced increase in DAG appear to be at least partly derived from increased de novo synthesis of PA.

  10. 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.

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

    PubMed

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

    2016-08-01

    [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. PMID:27630426

  12. 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. PMID:27630426

  13. Promising school-based strategies and intervention guidelines to increase physical activity of adolescents.

    PubMed

    Murillo Pardo, Berta; García Bengoechea, Enrique; Generelo Lanaspa, Eduardo; Bush, Paula L; Zaragoza Casterad, Javier; Julián Clemente, José A; García González, Luis

    2013-06-01

    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 measurement) and reviewed 52 intervention articles and 21 review articles. We identified several promising strategies and grouped into five broad intervention guidelines. These guidelines are as follows: (i) design multi-component interventions that foster the empowerment of members of the school community; (ii) develop improvements to Physical Education curricula as a strategy to promote physical activity to adolescents; (iii) design and implement non-curricular programmes and activities to promote physical activity; (iv) include computer-tailored interventions during the implementation and monitoring of physical activity promotion programmes and (v) design and implement specific strategies that respond to the interests and needs of girls. On the basis of our review of the adolescent physical activity promotion literature, we suggest that these five guidelines should be taken into account in school-based interventions geared towards achieving an increase in adolescent physical activity.

  14. Restricting opportunities to be active during school time: do children compensate by increasing physical activity levels after school?

    PubMed

    Dale, D; Corbin, C B; Dale, K S

    2000-09-01

    Opportunities for children to be physically active during school time are sparse and becoming increasingly so. The purpose of this investigation was to determine if children would compensate for school days (9 a.m.-3 p.m.) of restricted physical activity opportunities by increasing activity levels after school (3 p.m.-7:30 p.m.). Third and fourth grade children (N = 76) each wore a CSA accelerometer for 4 nonconsecutive days. Two days were categorized as active--during school, all children participated in outdoor recess and physical education class. Two days were categorized as restricted--all children spent their recess time indoors at a computer terminal, and no physical education class was scheduled. Dependent t tests revealed that children did not compensate for a sedentary school day by increasing their levels of physical activity after school. In fact, average movement counts per minute were higher in the 3 p.m.-7:30 p.m. period following the active day (525 counts.min-1) versus the restricted day (186 counts.min-1). These findings suggest cause for concern if children's opportunities to be active within school time are limited. Several reasons are given as to why children did not compensate or "make up" for the physical activity opportunities missed during the restricted school day.

  15. 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

  16. 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…

  17. 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'.

  18. 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

  19. Heparanase procoagulant activity, factor Xa, and plasminogen activator inhibitor 1 are increased in shift work female nurses.

    PubMed

    Nadir, Yona; Saharov, Gleb; Hoffman, Ron; Keren-Politansky, Anat; Tzoran, Inna; Brenner, Benjamin; Shochat, Tamar

    2015-07-01

    Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underlying mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation system. In the present study, a comparison of coagulation markers among healthy shift working (SW) vs. healthy daytime working (DW) female nurses was performed. Thirty SW and 30 DW female nurses were enrolled. For each of the 60 participants, blood was drawn between 7:00 and 8:00 a.m. and at least 8 h after the last work shift. Plasma was studied for coagulation marker that included TF/heparanase procoagulant activity, TF activity, heparanase procoagulant activity, heparanase level, factor Xa level, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-antiplasmin, fibrinogen, global protein C, von Willebrand factor, and D-dimer by chromogenic assays and enzyme-linked immunosorbent assays (ELISAs). Sleep quality was assessed by self-report according to the Pittsburgh Sleep Quality Index. The heparanase procoagulant activity increased by 2-fold and the TF/heparanase procoagulant activity increased by 1.5-fold in SW nurses compared to DW nurses (P < 0.05). Factor Xa levels and PAI-1 levels were significantly higher among SW nurses compared to the DW group (22 vs. 18 ng/ml, P < 0.05, and 32 vs. 22 ng/ml, P < 0.005, respectively). No significant differences were found in the other tested coagulation markers between the study groups. Heparanase procoagulant activity, factor Xa level, and PAI-1 level were significantly higher in SW nurses compared to the DW group. These alterations of blood coagulation activation may potentially contribute to cardiovascular and cancer morbidity.

  20. 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

  1. Increased anterior insula activity in anxious individuals is linked to diminished perceived control

    PubMed Central

    Alvarez, R P; Kirlic, N; Misaki, M; Bodurka, J; Rhudy, J L; Paulus, M P; Drevets, W C

    2015-01-01

    Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals. PMID:26125154

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

    PubMed Central

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

    2007-01-01

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

  3. 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.

  4. 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

  5. Rapid increases in ventilation accompany the transition from passive to active movement.

    PubMed

    Bell, Harold J; Duffin, James

    2006-06-01

    We used a novel movement transition technique to look for evidence of a rapid onset drive to breathe related to the active component of exercise in humans. Ten volunteers performed the following transitions in a specially designed tandem exercise chair apparatus: rest to passive movement, passive to active movement, and rest to active movement. The transition from rest to active exercise was accompanied by an immediate increase in ventilation, as was the transition from rest to passive leg movement (Delta = 6.06 +/- 1.09 l min(-1), p < 0.001 and Delta = 3.30 +/- 0.57 l min(-1), p = 0.002, respectively). When subjects actively assumed the leg movements, ventilation again increased immediately and significantly (Delta = 2.55 +/- 0.52 l min(-1), p = 0.032). Ventilation at the first point of active exercise was the same when started either from rest or from a background of passive leg movement (p = 1.00). We conclude that the use of a transition from passive to active leg movements in humans recruits a ventilatory drive related to the active component of exercise, and this can be discerned as a rapid increase in breathing.

  6. Cytochrome oxidase activity is increased in +/Lc Purkinje cells destined to die.

    PubMed

    Vogel, M W; Fan, H; Sydnor, J; Guidetti, P

    2001-10-01

    +/Lc Purkinje cells degenerate postnatally because of a gain-of-function mutation in the delta2 glutamate receptor (Grid2) that causes a constitutive Na+ current leak. The effect of the resulting chronic depolarization on Purkinje cell metabolism was investigated by measuring levels of cytochrome oxidase (COX) activity in Purkinje cell dendrites using quantitative densitometry. Analysis of wild type controls and +/Lc mutants at P10, P15 and P25 showed that levels of COX activity were significantly increased above control levels by P15 and continued to increase through P25. The increase in COX activity is likely to reflect an increase in oxidative phosphorylation to accommodate the energy demands of removing excess Na+ and Ca2+ entering the Purkinje cells in response to the Grid2 leak current.

  7. Peripheral Sensitization Increases Opioid Receptor Expression and Activation by Crotalphine in Rats

    PubMed Central

    Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

    2014-01-01

    Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. PMID:24594607

  8. Peripheral sensitization increases opioid receptor expression and activation by crotalphine in rats.

    PubMed

    Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

    2014-01-01

    Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids.

  9. Increased expression of the Ras suppressor Rsu-1 enhances Erk-2 activation and inhibits Jun kinase activation.

    PubMed

    Masuelli, L; Cutler, M L

    1996-10-01

    Studies were undertaken to determine the effect of the Ras suppressor Rsu-1 on Ras signal transduction pathways in two different cell backgrounds. An expression vector containing the mouse rsu-1 cDNA under the control of a mouse mammary tumor virus promoter was introduced into NIH 3T3 cells and the pheochromocytoma cell line PC12. Cell lines developed in the NIH 3T3 background expressed p33rsu-1 at approximately twice the normal endogenous level. However, PC12 cell clones which expressed p33rsu-1 at an increased level in a regulatable fashion in response to dexamethasone were isolated. Analysis of proteins involved in regulation of Ras and responsive to Ras signal transduction revealed similar changes in the two cell backgrounds in the presence of elevated p33rsu-1. There was an increase in the level of SOS, the guanine nucleotide exchange factor, and an increase in the percentage of GTP-bound Ras. In addition, there was an increase in the amount of p120 Ras-specific GTPase-activating protein (GAP) and GAP-associated p190. However, a decrease in Ras GTPase-activating activity was detected in lysates of the Rsu-1 transfectants, and immunoprecipitated p120 GAP from the Rsu-1 transfectants showed less Ras GTPase-activating activity than GAP from control cells. Activation of Erk-2 kinase by growth factor and tetradecanyol phorbol acetate was greater in the Rsu-1 transfectants than in control cells. However, c-Jun amino-terminal kinase activity (Jun kinase) was not activatable by epidermal growth factor in Rsu-1 PC12 cell transfectants, in contrast to the PC12 vector control cell line. Transient expression of p33rsu-1 in Cos1 cells following cotransfection with either hemagglutinin-tagged Jun kinase or hemagglutinin-tagged Erk-2 revealed that Rsu-1 expression inhibited constitutive Jun kinase activity while enhancing Erk-2 activity. Detection of in vitro binding of Rsu-1 to Raf-1 suggested that in Rsu-1 transfectants, increased activation of the Raf-1 pathway occurred

  10. Fixed Foot Balance Training Increases Rectus Femoris Activation During Landing and Jump Height in Recreationally Active Women

    PubMed Central

    Kean, Crystal O.; Behm, David G.; Young, Warren B.

    2006-01-01

    The objective of this study was to determine the effects of fixed foot and functionally directed balance training on static balance time, muscle activation during landing, vertical jump height and sprint time. Twenty-four recreationally active females were tested pre- and post-training (fixed foot balance training, n= 11, functionally directed balance training, n = 7 and control group, n = 6). Experimental subjects completed either fixed foot or functionally directed balance exercises 4 times/week for 6 weeks. Surface electromyography (EMG) was used to assess preparatory and reactive muscle activity of the rectus femoris (RF), biceps femoris (BF), and the soleus during one- and two-foot landings following a jump. Maximum vertical jump height, static balance and 20-meter sprint times were also examined. The fixed foot balance-training group showed a 33% improvement (p < 0.05) in static balance time and 9% improvement in jump height. Neither type of training improved sprint times. Further analysis revealed significant (p < 0.05) overall (data collapsed over groups and legs) increases in reactive RF activity when landing. Independently, the fixed foot balance group showed a 33% increase in reactive RF activity (p < 0.01). Overall, there was also significantly less reactive co-activation following training (p < 0.05). It appears that fixed foot balance training for recreationally active women may provide greater RF activity when landing and increased countermovement jump height. Key points Balance training increased rectus femoris EMG activity upon landing from a stride. Fixed foot balance training improved countermovement jump height. Neither fixed foot nor functionally directed balance training elicited changes in sprint times. PMID:24198691

  11. Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity.

    PubMed

    Mamoon, A M; Smith, J; Baker, R C; Farley, J M

    1999-01-01

    Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.

  12. Running increases neurogenesis without retinoic acid receptor activation in the adult mouse dentate gyrus.

    PubMed

    Aberg, Elin; Perlmann, Thomas; Olson, Lars; Brené, Stefan

    2008-01-01

    Both vitamin A deficiency and high doses of retinoids can result in learning and memory impairments, depression as well as decreases in cell proliferation, neurogenesis and cell survival. Physical activity enhances hippocampal neurogenesis and can also exert an antidepressant effect. Here we elucidate a putative link between running, retinoid signaling, and neurogenesis in hippocampus. Adult transgenic reporter mice designed to detect ligand-activated retinoic acid receptors (RAR) or retinoid X receptors (RXR) were used to localize the distribution of activated RAR or RXR at the single-cell level in the brain. Two months of voluntary wheel-running induced an increase in hippocampal neurogenesis as indicated by an almost two-fold increase in doublecortin-immunoreactive cells. Running activity was correlated with neurogenesis. Under basal conditions a distinct pattern of RAR-activated cells was detected in the granule cell layer of the dentate gyrus (DG), thalamus, and cerebral cortex layers 3-4 and to a lesser extent in hippocampal pyramidal cell layers CA1-CA3. Running did not change the number of RAR-activated cells in the DG. There was no correlation between running and RAR activation or between RAR activation and neurogenesis in the DG of hippocampus. Only a few scattered activated retinoid X receptors were found in the DG under basal conditions and after wheel-running, but RXR was detected in other areas such as in the hilus region of hippocampus and in layer VI of cortex cerebri. RAR agonists affect mood in humans and reduce neurogenesis, learning and memory in animal models. In our study, long-term running increased neurogenesis but did not alter RAR ligand activation in the DG in individually housed mice. Thus, our data suggest that the effects of exercise on neurogenesis and other plasticity changes in the hippocampal formation are mediated by mechanisms that do not involve retinoid receptor activation.

  13. Changes in muscle activation patterns when running step rate is increased.

    PubMed

    Chumanov, Elizabeth S; Wille, Christa M; Michalski, Max P; Heiderscheit, Bryan C

    2012-06-01

    Running with a step rate 5-10% greater than one's preferred can substantially reduce lower extremity joint moments and powers, and has been suggested as a possible strategy to aid in running injury management. The purpose of this study was to examine how neuromuscular activity changes with an increase in step rate during running. Forty-five injury-free, recreational runners participated in this study. Three-dimensional motion, ground reaction forces, and electromyography (EMG) of 8 muscles (rectus femoris, vastus lateralis, medial gastrocnemius, tibialis anterior, medial and lateral hamstrings, and gluteus medius and maximus) were recorded as each subject ran at their preferred speed for three different step rate conditions: preferred, +5% and +10% of preferred. Outcome measures included mean normalized EMG activity for each muscle at specific periods during the gait cycle. Muscle activities were found to predominantly increase during late swing, with no significant change in activities during the loading response. This increased muscle activity in anticipation of foot-ground contact likely alters the landing posture of the limb and the subsequent negative work performed by the joints during stance phase. Further, the increased activity observed in the gluteus maximus and medius suggests running with a greater step rate may have therapeutic benefits to those with anterior knee pain.

  14. Hyperthyroidism increases the uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+-ATPase.

    PubMed Central

    Arruda, Ana Paula; Da-Silva, Wagner S; Carvalho, Denise P; De Meis, Leopoldo

    2003-01-01

    The sarcoplasmic reticulum Ca2+-ATPase is able to modulate the distribution of energy released during ATP hydrolysis, so that a portion of energy is used for Ca2+ transport (coupled ATPase activity) and a portion is converted into heat (uncoupled ATPase activity). In this report it is shown that T4 administration to rabbits promotes an increase in the rates of both the uncoupled ATPase activity and heat production in sarcoplasmic reticulum vesicles, and that the degree of activation varies depending on the muscle type used. In white muscles hyperthyroidism promotes a 0.8-fold increase of the uncoupled ATPase activity and in red muscle a 4-fold increase. The yield of vesicles from hyperthyroid muscles is 3-4-fold larger than that obtained from normal muscles; thus the rate of heat production by the Ca2+-ATPase expressed in terms of g of muscle in hyperthyroidism is increased by a factor of 3.6 in white muscles and 12.0 in red muscles. The data presented suggest that the Ca2+-ATPase uncoupled activity may represent one of the heat sources that contributes to the enhanced thermogenesis noted in hyperthyroidism. PMID:12887329

  15. Large contribution of sea surface warming to recent increase in Atlantic hurricane activity.

    PubMed

    Saunders, Mark A; Lea, Adam S

    2008-01-31

    Atlantic hurricane activity has increased significantly since 1995 (refs 1-4), but the underlying causes of this increase remain uncertain. It is widely thought that rising Atlantic sea surface temperatures have had a role in this, but the magnitude of this contribution is not known. Here we quantify this contribution for storms that formed in the tropical North Atlantic, Caribbean Sea and Gulf of Mexico; these regions together account for most of the hurricanes that make landfall in the United States. We show that a statistical model based on two environmental variables--local sea surface temperature and an atmospheric wind field--can replicate a large proportion of the variance in tropical Atlantic hurricane frequency and activity between 1965 and 2005. We then remove the influence of the atmospheric wind field to assess the contribution of sea surface temperature. Our results indicate that the sensitivity of tropical Atlantic hurricane activity to August-September sea surface temperature over the period we consider is such that a 0.5 degrees C increase in sea surface temperature is associated with a approximately 40% increase in hurricane frequency and activity. The results also indicate that local sea surface warming was responsible for approximately 40% of the increase in hurricane activity relative to the 1950-2000 average between 1996 and 2005. Our analysis does not identify whether warming induced by greenhouse gases contributed to the increase in hurricane activity, but the ability of climate models to reproduce the observed relationship between hurricanes and sea surface temperature will serve as a useful means of assessing whether they are likely to provide reliable projections of future changes in Atlantic hurricane activity.

  16. Exogenous methyl jasmonate treatment increases glucosinolate biosynthesis and quinone reductase activity in kale leaf tissue.

    PubMed

    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 combined

  17. Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution.

    PubMed

    Martinez, Ronny; Jakob, Felix; Tu, Ran; Siegert, Petra; Maurer, Karl-Heinz; Schwaneberg, Ulrich

    2013-03-01

    Bacillus gibsonii Alkaline Protease (BgAP) is a recently reported subtilisin protease exhibiting activity and stability properties suitable for applications in laundry and dish washing detergents. However, BgAP suffers from a significant decrease of activity at low temperatures. In order to increase BgAP activity at 15°C, a directed evolution campaign based on the SeSaM random mutagenesis method was performed. An optimized microtiter plate expression system in B. subtilis was established and classical proteolytic detection methods were adapted for high throughput screening. In parallel, the libraries were screened for increased residual proteolytic activity after incubation at 58°C. Three iterative rounds of directed BgAP evolution yielded a set of BgAP variants with increased specific activity (K(cat)) at 15°C and increased thermal resistance. Recombination of both sets of amino acid substitutions resulted finally in variant MF1 with a 1.5-fold increased specific activity (15°C) and over 100 times prolonged half-life at 60°C (224 min compared to 2 min of the WT BgAP). None of the introduced amino acid substitutions were close to the active site of BgAP. Activity-altering amino acid substitutions were from non-charged to non-charged or from sterically demanding to less demanding. Thermal stability improvements were achieved by substitutions to negatively charged amino acids in loop areas of the BgAP surface which probably fostered ionic and hydrogen bonds interactions.

  18. 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

  19. 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

  20. 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

  1. 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}.

  2. 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

  3. 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

  4. 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

  5. Increased β-cyanoalanine nitrilase activity improves cyanide tolerance and assimilation in Arabidopsis.

    PubMed

    O'Leary, Brendan; Preston, Gail M; Sweetlove, Lee J

    2014-01-01

    Plants naturally produce cyanide (CN) which is maintained at low levels in their cells by a process of rapid assimilation. However, high concentrations of environmental CN associated with activities such as industrial pollution are toxic to plants. There is thus an interest in increasing the CN detoxification capacity of plants as a potential route to phytoremediation. Here, Arabidopsis seedlings overexpressing the Pseudomonas fluorescens β-cyanoalanine nitrilase pinA were compared with wild-type and a β-cyanoalanine nitrilase knockout line (ΔAtnit4) for growth in the presence of exogenous CN. After incubation with CN, +PfpinA seedlings had increased root length, increased fresh weight, and decreased leaf bleaching compared with wild-type, indicating increased CN tolerance. The increased tolerance was achieved without an increase in β-cyanoalanine synthase activity, the other enzyme in the cyanide assimilation pathway, suggesting that nitrilase activity is the limiting factor for cyanide detoxification. Labeling experiments with [¹³C]KCN demonstrated that the altered CN tolerance could be explained by differences in flux from CN to Asn caused by altered β-cyanoalanine nitrilase activity. Metabolite profiling after CN treatment provided new insight into downstream metabolism, revealing onward metabolism of Asn by the photorespiratory nitrogen cycle and accumulation of aromatic amino acids.

  6. 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.

  7. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    PubMed

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO.

  8. 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

  9. 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

  10. Interventions to Increase Physical Activity in Children Aged 2-5 Years: A Systematic Review.

    PubMed

    Ling, Jiying; Robbins, Lorraine B; Wen, Fujun; Peng, Wei

    2015-08-01

    Comprehensive evaluation of prior interventions designed to increase preschoolers' physical activity is lacking. This systematic review aimed to examine the effect of interventions on objectively measured physical activity in children aged 2-5 years. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In May 2014, we searched PubMed, CINAHL, PsycINFO, ERIC, SPORTDiscus, Cochrane, and Embase. Two reviewers independently identified and appraised the studies. Twenty-four articles describing 23 independent studies and 20 unique interventions met inclusion criteria. Of the 8 interventions resulting in a significant effect in objectively measured physical activity, all were center-based and included a structured physical activity component, 6 included multiple components, 5 integrated theories or models, and 4 actively involved parents. Seven of the 8 were randomized controlled trials. Due to the heterogeneity of the study designs, physical activity measures, and interventions, drawing definitive conclusions was difficult. Although the overall intervention effect was less than optimal, the review indicated that theory-driven, multicomponent interventions including a structured physical activity component and targeting both parents and their children may be a promising approach for increasing preschoolers' physical activity and warrant continued investigation using rigorous designs to identify those that are most effective.

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

    PubMed

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

    2015-09-01

    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.

  12. 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

  13. Peers increase adolescent risk taking by enhancing activity in the brain’s reward circuitry

    PubMed Central

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

    2010-01-01

    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 simulated driving task. Participants completed one task block while alone, and one block while their performance was observed by peers in an adjacent room. During peer observation blocks, adolescents selectively demonstrated greater activation in reward-related brain regions, including the ventral striatum and orbitofrontal cortex, and activity in these regions predicted subsequent risk taking. Brain areas associated with cognitive control were less strongly recruited by adolescents than adults, but activity in the cognitive control system did not vary with social context. Results suggest that the presence of peers increases adolescent risk taking by heightening sensitivity to the potential reward value of risky decisions. PMID:21499511

  14. Engineering of TM1459 from Thermotoga maritima for Increased Oxidative Alkene Cleavage Activity

    PubMed Central

    Fink, Matthias; Trunk, Sarah; Hall, Mélanie; Schwab, Helmut; Steiner, Kerstin

    2016-01-01

    Oxidative cleavage of alkenes is a widely employed process allowing oxyfunctionalization to corresponding carbonyl compounds. Recently, a novel biocatalytic oxidative alkene cleavage activity on styrene derivatives was identified in TM1459 from Thermotoga maritima. In this work we engineered the enzyme by site-saturation mutagenesis of active site amino acids to increase its activity and to broaden its substrate scope. A high-throughput assay for the detection of the ketone products was successfully developed. Several variants with up to twofold improved conversion level of styrene derivatives were successfully identified. Especially, changes in or removal of the C-terminus of TM1459 increased the activity most significantly. These best variants also displayed a slightly enlarged substrate scope. PMID:27713741

  15. 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

  16. Ionizing radiations increase the activity of the cell surface glycohydrolases and the plasma membrane ceramide content.

    PubMed

    Aureli, Massimo; Bassi, Rosaria; Prinetti, Alessandro; Chiricozzi, Elena; Pappalardi, Brigida; Chigorno, Vanna; Di Muzio, Nadia; Loberto, Nicoletta; Sonnino, Sandro

    2012-12-01

    We detected significant levels of β-glucosidase, β-galactosidase, sialidase Neu3 and sphingomyelinase activities associated with the plasma membrane of fibroblasts from normal and Niemann-Pick subjects and of cells from breast, ovary, colon and neuroblastoma tumors in culture. All of the cells subjected to ionizing radiations showed an increase of the activity of plasma membrane β-glucosidase, β-galactosidase and sialidase Neu3, in addition of the well known increase of activity of plasma membrane sphingomyelinase, under similar conditions. Human breast cancer cell line T47D was studied in detail. In these cells the increase of activity of β-glucosidase and β-galactosidase was parallel to the increase of irradiation dose up to 60 Gy and continued with time, at least up to 72 h from irradiation. β-glucosidase increased up to 17 times and β-galactosidase up to 40 times with respect to control. Sialidase Neu3 and sphingomyelinase increased about 2 times at a dose of 20 Gy but no further significant differences were observed with increase of radiation dose and time. After irradiation, we observed a reduction of cell proliferation, an increase of apoptotic cell death and an increase of plasma membrane ceramide up to 3 times, with respect to control cells. Tritiated GM3 ganglioside has been administered to T47D cells under conditions that prevented the lysosomal catabolism. GM3 became component of the plasma membranes and was transformed into LacCer, GlcCer and ceramide. The quantity of ceramide produced in irradiated cells was about two times that of control cells.

  17. Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease▿

    PubMed Central

    Dhiman, Monisha; Estrada-Franco, Jose Guillermo; Pando, Jasmine M.; Ramirez-Aguilar, Francisco J.; Spratt, Heidi; Vazquez-Corzo, Sara; Perez-Molina, Gladys; Gallegos-Sandoval, Rosa; Moreno, Roberto; Garg, Nisha Jain

    2009-01-01

    In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O2− source) and nitrate/nitrite contents (denotes iNOS activation and NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological NO and O2− concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies

  18. 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

  19. Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration.

    PubMed

    Feng, Juan; Lü, Silin; Ding, Yanhong; Zheng, Ming; Wang, Xian

    2016-06-01

    Hyperhomocysteinemia (HHcy) accelerates atherosclerosis by increasing proliferation and stimulating cytokine secretion in T cells. However, whether homocysteine (Hcy)-mediated T cell activation is associated with metabolic reprogramming is unclear. Here, our in vivo and in vitro studies showed that Hcy-stimulated splenic T-cell activation in mice was accompanied by increased levels of mitochondrial reactive oxygen species (ROS) and calcium, mitochondrial mass and respiration. Inhibiting mitochondrial ROS production and calcium signals or blocking mitochondrial respiration largely blunted Hcy-induced T-cell interferon γ (IFN-γ) secretion and proliferation. Hcy also enhanced endoplasmic reticulum (ER) stress in T cells, and inhibition of ER stress with 4-phenylbutyric acid blocked Hcy-induced T-cell activation. Mechanistically, Hcy increased ER-mitochondria coupling, and uncoupling ER-mitochondria by the microtubule inhibitor nocodazole attenuated Hcy-stimulated mitochondrial reprogramming, IFN-γ secretion and proliferation in T cells, suggesting that juxtaposition of ER and mitochondria is required for Hcy-promoted mitochondrial function and T-cell activation. In conclusion, Hcy promotes T-cell activation by increasing ER-mitochondria coupling and regulating metabolic reprogramming.

  20. Ribulose diphosphate carboxylase synthesis in euglena: increased enzyme activity after transferring regreening cells to darkness.

    PubMed

    Lord, J M; Merrett, M J

    1975-05-01

    The transfer of dark-grown cultures of Euglena gracilis Klebs strain Z regreening in the light back into darkness resulted in a dramatic increase in ribulose diphosphate carboxylase activity. On a culture volume basis activity increased 4-fold over a 24-hour dark period, although on a protein basis activity declined because of rapid cell division. Mixed assays with light- and dark-growing cell extracts provided no evidence for the removal of an inhibitor of ribulose diphosphate carboxylase upon transferring regreening cells back to darkness. Although ribulose diphosphate carboxylase activity increased over a 24-hour dark period, there was no concomitant increase in the potential of the cells for photosynthetic carbon dioxide fixation.Higher light intensities than the optimum for ribulose diphosphate carboxylase synthesis during regreening resulted in a greater relative rate of synthesis on transfer to darkness so that the maximum activity of ribulose diphosphate carboxylase reached in the dark was constant, regardless of light intensity during regreening. A tentative hypothesis to explain these results is that the synthesis of the large and small subunits of ribulose diphosphate carboxylase occur at different stages of cell development, light being necessary for the synthesis of the large subunit and also for regulating the synthesis of the small subunit.

  1. K153R polymorphism in myostatin gene increases the rate of promyostatin activation by furin.

    PubMed

    Szláma, György; Trexler, Mária; Buday, László; Patthy, László

    2015-01-30

    Recent studies demonstrated an association between the K153R polymorphism in the myostatin gene with extreme longevity, lower muscle strength and obesity but the molecular basis of these associations has not been clarified. Here, we show that the K153R mutation significantly increases the rate of proteolysis of promyostatin by furin, but has no effect on the activity of the latent complex or the cleavage of the latent complex by bone morphogenetic protein 1 (BMP-1). The increased rate of activation of K153R mutant promyostatin may explain why this polymorphism is associated with obesity, lower muscle strength and extension of lifespan.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus.

    PubMed

    Brambila-Tapia, Aniel J L; Gámez-Nava, Jorge I; Salazar-Páramo, Mario; Munoz-Valle, José F; González-López, Laura; Llamas-Covarrubias, Mara A; Gutiérrez-Urena, Sergio R; Vázquez-Del Mercado, Mónica; Dávalos-Rodríguez, Ingrid P

    2011-10-01

    CD28 is one of the main activator receptors involved in systemic lupus erythematosus (SLE) pathogenesis, and its expression and serum levels are significantly higher in patients with SLE and other autoimmune diseases than in healthy controls (HC). However, it is unknown whether this increase is associated with specific organ damage. Therefore, our objective was to measure the CD28 levels in serum from SLE and HC groups to confirm the CD28 serum levels increase, as reported previously, and to determine whether this increase was associated with specific organ activity and the SLE Disease Activity Index (SLEDAI). Forty SLE patients and 40 matched HC were included, and the age, disease duration, SLEDAI and Mexican SLEDAI were recorded for the SLE group. CD28 serum levels were measured by ELISA. There was a statistically significant increase in the CD28 serum levels of SLE patients compared to controls (p = 0.039); however, we did not find any significant correlation with disease activity indices or organ involvement, although we found a significant but low correlation with C3. Our results and a review of the literature suggest that the increase in CD28 serum levels may be the result of CD28 gene overexpression, which could be related to the decrease in CD28+ T cells, T-cell hyporesponsiveness and immune impairment that occurs in SLE.

  8. 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

  9. 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.

  10. Warming and earlier spring increase Western U.S. forest wildfire activity

    USGS Publications Warehouse

    Westerling, A.L.; Hidalgo, H.G.; Cayan, D.R.; Swetnam, T.W.

    2006-01-01

    Western United States forest wildfire activity is widely thought to have increased in recent decades, yet neither the extent of recent changes nor the degree to which climate may be driving regional changes in wildfire has been systematically documented. Much of the public and scientific discussion of changes in western United States wildfire has focused instead on the effects of 19th- and 20th-century land-use history. We compiled a comprehensive database of large wildfires in western United States forests since 1970 and compared it with hydroclimatic and land-surface data. Here, we show that large wildfire activity increased suddenly and markedly in the mid-1980s, with higher large-wildfire frequency, longer wildfire durations, and longer wildfire seasons. The greatest increases occurred in mid-elevation, Northern Rockies forests, where land-use histories have relatively little effect on fire risks and are strongly associated with increased spring and summer temperatures and an earlier spring snowmelt.

  11. Deletion of the Neurotrophic Factor neudesin Prevents Diet-induced Obesity by Increased Sympathetic Activity

    PubMed Central

    Ohta, Hiroya; Konishi, Morichika; Kobayashi, Yusuke; Kashio, Atsuki; Mochiyama, Takayuki; Matsumura, Shigenobu; Inoue, Kazuo; Fushiki, Tohru; Nakao, Kazuwa; Kimura, Ikuo; Itoh, Nobuyuki

    2015-01-01

    Some neurotrophic factors, which are potent regulators of neuronal development and function, have recently been implicated in the control of energy balance by increasing energy expenditure. We previously identified neudesin as a novel neurotrophic factor with potential roles in the central nervous system. Although neudesin is also expressed in various peripheral tissues including adipose tissue, its physiological roles have not yet been elucidated. We found that neudesin knockout (KO) mice were resistant to high-fat diet-induced obesity and obesity-related metabolic dysfunctions. neudesin KO mice exhibited increased energy expenditure due to increased sympathetic activity, which resulted in increased heat production and fatty acid oxidation in brown adipose tissue and enhanced lipolysis in white adipose tissue. Thus, neudesin, which may be a negative regulator of sympathetic activity, could represent a novel regulator of the development of obesity and obesity-related metabolic dysfunctions. PMID:25955136

  12. 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.

  13. [Increase of rising activity of commercial yeasts by application of stress conditions during their propagation].

    PubMed

    Galvagno, M A; Cerrutti, P

    2004-01-01

    Rising activity determined as CO2 production of two commercial strains of Saccharomyces cerevisiae could be increased mainly in sweet bread doughs by introducing a "starvation/pulse feeding" schedule of sugar cane molasses during a fed-batch propagation. Such increase was strain dependent. Except for the trehalose intracellular level, other traits related to the yeast industrial performance were unaffected. Applicability of method for baker's yeast industrial production is discussed.

  14. Utilizing avidity to improve antifreeze protein activity: a type III antifreeze protein trimer exhibits increased thermal hysteresis activity.

    PubMed

    Can, Özge; Holland, Nolan B

    2013-12-01

    Antifreeze proteins (AFPs) are ice growth inhibitors that allow the survival of several species living at temperatures colder than the freezing point of their bodily fluids. AFP activity is commonly defined in terms of thermal hysteresis, which is the difference observed for the solution freezing and melting temperatures. Increasing the thermal hysteresis activity of these proteins, particularly at low concentrations, is of great interest because of their wide range of potential applications. In this study, we have designed and expressed one-, two-, and three-domain antifreeze proteins to improve thermal hysteresis activity through increased binding avidity. The three-domain type III AFP yielded significantly greater activity than the one- and two-domain proteins, reaching a thermal hysteresis of >1.6 °C at a concentration of <1 mM. To elucidate the basis of this increase, the data were fit to a multidomain protein adsorption model based on the classical Langmuir isotherm. Fits of the data to the modified isotherms yield values for the equilibrium binding constants for the adsorption of AFP to ice and indicate that protein surface coverage is proportional to thermal hysteresis activity.

  15. 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.

  16. AM fungal exudates activate MAP kinases in plant cells in dependence from cytosolic Ca(2+) increase.

    PubMed

    Francia, Doriana; Chiltz, Annick; Lo Schiavo, Fiorella; Pugin, Alain; Bonfante, Paola; Cardinale, Francesca

    2011-09-01

    The molecular dialogue occurring prior to direct contact between the fungal and plant partners of arbuscular-mycorrhizal (AM) symbioses begins with the release of fungal elicitors, so far only partially identified chemically, which can activate specific signaling pathways in the host plant. We show here that the activation of MAPK is also induced by exudates of germinating spores of Gigaspora margarita in cultured cells of the non-leguminous species tobacco (Nicotiana tabacum), as well as in those of the model legume Lotus japonicus. MAPK activity peaked about 15 min after the exposure of the host cells to the fungal exudates (FE). FE were also responsible for a rapid and transient increase in free cytosolic Ca(2+) in Nicotiana plumbaginifolia and tobacco cells, and pre-treatment with a Ca(2+)-channel blocker (La(3+)) showed that in these cells, MAPK activation was dependent on the cytosolic Ca(2+) increase. A partial dependence of MAPK activity on the common Sym pathway could be demonstrated for a cell line of L. japonicus defective for LjSym4 and hence unable to establish an AM symbiosis. Our results show that MAPK activation is triggered by an FE-induced cytosolic Ca(2+) transient, and that a Sym genetic determinant acts to modulate the intensity and duration of this activity.

  17. Improvements in knee biomechanics during walking are associated with increased physical activity after total knee arthroplasty.

    PubMed

    Arnold, John B; Mackintosh, Shylie; Olds, Timothy S; Jones, Sara; Thewlis, Dominic

    2015-12-01

    Total knee arthroplasty (TKA) in people with knee osteoarthritis increases knee-specific and general physical function, but it has not been established if there is a relationship between changes in these elements of functional ability. This study investigated changes and relationships between knee biomechanics during walking, physical activity, and use of time after TKA. Fifteen people awaiting TKA underwent 3D gait analysis before and six months after surgery. Physical activity and use of time were determined in free-living conditions from a high resolution 24-h activity recall. After surgery, participants displayed significant improvements in sagittal plane knee biomechanics and improved their physical activity profiles, standing for 105 more minutes (p=0.001) and performing 64 min more inside chores on average per day (p=0.008). Changes in sagittal plane knee range of motion (ROM) and peak knee flexion positively correlated with changes in total daily energy expenditure, time spent undertaking moderate to vigorous physical activity, inside chores and passive transport (r=0.52-0.66, p=0.005-0.047). Restoration of knee function occurs in parallel and is associated with improvements in physical activity and use of time after TKA. Increased functional knee ROM is required to support improvements in total and context specific physical activity.

  18. 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

  19. Comparative Effectiveness of After-School Programs to Increase Physical Activity

    PubMed Central

    Gesell, Sabina B.; Sommer, Evan C.; Lambert, E. Warren; Vides de Andrade, Ana Regina; Davis, Lauren; Beech, Bettina M.; Mitchell, Stephanie J.; Neloms, Stevon; Ryan, Colleen K.

    2013-01-01

    Background. We conducted a comparative effectiveness analysis to evaluate the difference in the amount of physical activity children engaged in when enrolled in a physical activity-enhanced after-school program based in a community recreation center versus a standard school-based after-school program. Methods. The study was a natural experiment with 54 elementary school children attending the community ASP and 37 attending the school-based ASP. Accelerometry was used to measure physical activity. Data were collected at baseline, 6 weeks, and 12 weeks, with 91% retention. Results. At baseline, 43% of the multiethnic sample was overweight/obese, and the mean age was 7.9 years (SD = 1.7). Linear latent growth models suggested that the average difference between the two groups of children at Week 12 was 14.7 percentage points in moderate-vigorous physical activity (P < .001). Cost analysis suggested that children attending traditional school-based ASPs—at an average cost of $17.67 per day—would need an additional daily investment of $1.59 per child for 12 weeks to increase their moderate-vigorous physical activity by a model-implied 14.7 percentage points. Conclusions. A low-cost, alternative after-school program featuring adult-led physical activities in a community recreation center was associated with increased physical activity compared to standard-of-care school-based after-school program. PMID:23984052

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

    PubMed

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

    2010-04-01

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

  1. No Evidence for Activity Adjustment in Response to Increased Density in Daphnia magna.

    PubMed

    Sereni, Laura; Einum, Sigurd

    2015-01-01

    Increased population density may lead to a decrease in energy available for growth and reproduction via effects on the activity level of individuals. Whilst this may be of particular importance for organisms that compete for defendable resources and/or have a high frequency of social interactions, it is less obvious how individual activity should covary with population density when food resources are not defendable or direct interactions among individuals are negligible. Based on observations that there is a general negative relationship between population density and metabolism it has been suggested that organisms actively reduce activity under increased density to accommodate an expected decrease in food availability. However, in the absence of direct activity measurements the validity of this hypothesis is unclear. Here we test for such anticipatory adjustments of activity levels in the planktonic cladoceran Daphnia magna Straus, a filter feeder whose food resources are not defendable, meaning that density responses can be evaluated in the absence of direct interactions. We tested for changes in activity in response to two separate density cues, one being the direct physical and visual stimuli resulting from being in the vicinity of conspecifics ('direct density experiment'), and the other being the detection of olfactory cues in their environment ('olfactory cue experiment'). Ten genetically distinct clones were used to evaluate the potential for genetic variation in these responses. Our measures of activity were highly repeatable, and there was significant variation in activity among clones. Furthermore, this clonal variation was consistent in the 'direct density' and 'olfactory cue' experiments. The estimated evolvability of the trait (1.3-3.2%) was within the range typically observed in behavioural traits. However, there was no indication that the activity level of individuals respond to population density, either directly to actual density or to olfactory

  2. 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

  3. Increase of lipoprotein-lipase activity in skeletal muscle during heavy exercise. Relation to epinephrine excretion.

    PubMed

    Lithell, H; Cedermark, M; Fröberg, J; Tesch, P; Karlsson, J

    1981-11-01

    As part of the training programme for Swedish elite soldiers, a 10 day march is carried out with a heavy pack under active-service conditions. Six soldiers volunteered to take part in an investigation on the energy consumption with special regard to the lipid metabolism at different levels of physical effort. The degree of physical work was evaluated by continuous heart-rate recording and analysis of the excretion of epinephrine and norepinephrine in the urine. Fasting values of triglycerides and free fatty acids in blood plasma were determined and muscle biopsies (taken in the morning and in the afternoon) were analysed for lipoprotein-lipase (LPL) activity. After an overnight fast the free fatty acids were increased only in the mornings following days of heavy physical work. The plasma triglyceride concentrations were lowest in a morning proceeded by 3 days of heavy work. The muscle LPL activity in the morning was highest after a day of heavy work and lowest after days of rest. During days of heavy work this activity increased and was higher in the afternoon than in the morning. Muscle LPL activity in the afternoon was closely related to urinary excretion of epinephrine. The data indicate that LPL activity is elevated in the working skeletal muscle increasing the access of fatty acids. The degree of elevation is related to the degree of effort as described by the urinary excretion of morning. Muscle LPL activity in the afternoon was closely related to urinary excretion of epinephrine. The data indicate that LPL activity is elevated in the working skeletal muscle increasing the access of fatty acids. The degree of elevation is related to the degree of effort as described by the urinary excretion of morning. Muscle LPL activity in the afternoon was closely related to urinary excretion of epinephrine. The data indicate that LPL activity is elevated in the working skeletal muscle increasing the access of fatty acids. The degree of elevation is related to the degree

  4. Ghrelin increases food intake, swimming activity and growth in juvenile brown trout (Salmo trutta).

    PubMed

    Tinoco, Ana B; Näslund, Joacim; Delgado, María J; de Pedro, Nuria; Johnsson, Jörgen I; Jönsson, Elisabeth

    2014-01-30

    Several key functions of ghrelin are well conserved through vertebrate phylogeny. However, some of ghrelin's effects are contradictory and among teleosts only a limited number of species have been used in functional studies on food intake and foraging-related behaviors. Here we investigated the long-term effects of ghrelin on food intake, growth, swimming activity and aggressive contest behavior in one year old wild brown trout (Salmo trutta) using intraperitoneal implants. Food intake and swimming activity were individually recorded starting from day 1, and aggressive behavior was tested at day 11, after ghrelin implantation. Body weight and growth rate were measured from the beginning to the end of the experiment. Triglycerides and lipase activity in muscle and liver; monoaminergic activity in the telencephalon and brainstem; and neuropeptide Y (NPY) mRNA levels in the hypothalamus were analyzed. Ghrelin treatment was found to increase food intake and growth without modifying lipid deposition or lipid metabolism in liver and muscle. Ghrelin treatment led to an increased foraging activity and a trend towards a higher swimming activity. Moreover, ghrelin-treated fish showed a tendency to initiate more conflicts, but this motivation was not reflected in a higher ability to win the conflicts. No changes were observed in monoaminergic activity and NPY mRNA levels in the brain. Ghrelin is therefore suggested to act as an orexigenic hormone regulating behavior in juvenile wild brown trout. These actions are accompanied with an increased growth without the alteration of liver and muscle lipid metabolism and they do not seem to be mediated by changes in brain monoaminergic activity or hypothalamic expression of NPY.

  5. Activity-dependent alternative splicing increases persistent sodium current and promotes seizure

    PubMed Central

    Lin, Wei-Hsiang; Günay, Cengiz; Marley, Richard; Prinz, Astrid A.; Baines, Richard A.

    2012-01-01

    Activity of voltage-gated Na channels (Nav) is modified by alternative splicing. However, whether altered splicing of human Nav’s contributes to epilepsy remains to be conclusively shown. We show here that altered splicing of the Drosophila Nav (paralytic, DmNav) contributes to seizure-like behaviour in identified seizure-mutants. We focus attention on a pair of mutually-exclusive alternate exons (termed K and L), which form part of the voltage sensor (S4) in domain III of the expressed channel. The presence of exon L results in a large, non-inactivating, persistent INap. Many forms of human epilepsy are associated with an increase in this current. In wildtype (WT) Drosophila larvae ~70-80% of DmNav transcripts contain exon L, the remainder contain exon K. Splicing of DmNav to include exon L is increased to ~100% in both the slamdance and easily-shocked seizure-mutants. This change to splicing is prevented by reducing synaptic activity levels through exposure to the antiepileptic phenytoin or the inhibitory transmitter GABA. Conversely, enhancing synaptic activity in WT, by feeding of picrotoxin, is sufficient to increase INap and promote seizure through increased inclusion of exon L to 100%. We also show that the underlying activity-dependent mechanism requires the presence of Pasilla, an RNA-binding protein. Finally, we use computational modelling to show that increasing INap is sufficient to potentiate membrane excitability consistent with a seizure phenotype. Thus, increased synaptic excitation favors inclusion of exon L which, in turn, further increases neuronal excitability. Thus, at least in Drosophila, this self-reinforcing cycle may promote the incidence of seizure. PMID:22623672

  6. 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

  7. 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

  8. Cell Surface Epidermal Growth Factor Receptors Increase Src and c-Cbl Activity and Receptor Ubiquitylation*

    PubMed Central

    Parks, Eileen E.; Ceresa, Brian P.

    2014-01-01

    There is an established role for the endocytic pathway in regulation of epidermal growth factor receptor (EGFR) signaling to downstream effectors. However, because ligand-mediated EGFR endocytosis utilizes multiple “moving parts,” dissecting the spatial versus temporal contributions has been challenging. Blocking all endocytic trafficking can have unintended effects on other receptors as well as give rise to compensatory mechanisms, both of which impact interpretation of EGFR signaling. To overcome these limitations, we used epidermal growth factor (EGF) conjugated to polystyrene beads (EGF beads). EGF beads simultaneously activate the EGFR while blocking its endocytosis and allow analysis of EGFR signaling from the plasma membrane. Human telomerase immortalized corneal epithelial (hTCEpi) cells were used to model normal epithelial cell biology. In hTCEpi cells, both cell surface and intracellular EGFRs exhibited dose-dependent increases in effector activity after 15 min of ligand stimulation, but only the serine phosphorylation of signal transducer and activator of transcription 3 (STAT3) was statistically significant when accounting for receptor phosphorylation. However, over time with physiological levels of receptor phosphorylation, cell surface receptors produced either enhanced or sustained mitogen-activated protein kinase kinase (MEK), Casitas B-lineage lymphoma (c-Cbl), and the pro-oncogene Src activity. These increases in effector communication by cell surface receptors resulted in an increase in EGFR ubiquitylation with sustained ligand incubation. Together, these data indicate that spatial regulation of EGFR signaling may be an important regulatory mechanism in receptor down-regulation. PMID:25074934

  9. 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.

  10. Cocaine increases dopaminergic neuron and motor activity via midbrain α1 adrenergic signaling.

    PubMed

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

    2015-03-13

    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.

  11. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    PubMed Central

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  12. Increased activity of the complement system in the liver of patients with alcoholic hepatitis.

    PubMed

    Shen, Hong; French, Barbara A; Liu, Hui; Tillman, Brittany C; French, Samuel W

    2014-12-01

    Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH.

  13. 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.

  14. 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.

  15. Diabetes Promotes DMH-Induced Colorectal Cancer by Increasing the Activity of Glycolytic Enzymes in Rats

    PubMed Central

    Jia, Yanglei; Xu, Gang; Zhou, Wenjing; Wang, Zhenzheng; Meng, Linlin; Zhou, Songnan; Xu, Xia; Yuan, Huiqing; Tian, Keli

    2014-01-01

    The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats. PMID:25329503

  16. Increasing Play Skills of Children with Autism Using Activity Schedules and Correspondence Training.

    ERIC Educational Resources Information Center

    Morrison, Rebecca S.; Sainato, Diane M.; BenChaaban, Delia; Endo, Sayaka

    2002-01-01

    A study investigated the effectiveness of correspondence training and photographic activity schedules on the on-task and play correspondence behavior of four preschool children with autism in an inclusive setting. Results indicate that all participants' on-task and play correspondence behavior increased, while experimenter prompts gradually…

  17. 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.

  18. 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%.

  19. 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…

  20. 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

  1. 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.

  2. 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…

  3. 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…

  4. Pedometers and Brief E-Counseling: Increasing Physical Activity for Overweight Adults

    ERIC Educational Resources Information Center

    VanWormer, Jeffrey J.

    2004-01-01

    Physical inactivity has emerged as a public health epidemic and is associated with the rising obesity rate. A multiple-treatments reversal design was utilized to test whether pedometer-aided self-monitoring and brief e-counseling could help 3 overweight adults increase their physical activity. Dependent measures were taken for pedometer steps and…

  5. 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…

  6. Pedometers: A Strategy to Promote Increased Physical Activity among College Students

    ERIC Educational Resources Information Center

    Hackmann, Debra J.; Mintah, Joseph K.

    2010-01-01

    Inactive lifestyle behaviors are predominant in society, especially among the adult population. This study examined the issue of inactivity among college students. A pedometer was used as an intervention strategy, to increase awareness of, and motivate college students to achieve the minimum recommended amount of daily physical activity. A…

  7. Glucose deprivation increases tau phosphorylation via P38 mitogen-activated protein kinase.

    PubMed

    Lauretti, Elisabetta; Praticò, Domenico

    2015-12-01

    Alterations of glucose metabolism have been observed in Alzheimer's disease (AD) brain. Previous studies showed that glucose deprivation increases amyloidogenesis via a BACE-1-dependent mechanism. However, no data are available on the effect that this condition may have on tau phosphorylation. In this study, we exposed neuronal cells to a glucose-free medium and investigated the effect on tau phosphorylation. Compared with controls, cells incubated in the absence of glucose had a significant increase in tau phosphorylation at epitopes Ser202/Thr205 and Ser404, which was associated with a selective activation of the P38 mitogen-activated protein kinase. Pharmacological inhibition of this kinase prevented the increase in tau phosphorylation, while fluorescence studies revealed its co-localization with phosphorylated tau. The activation of P38 was secondary to the action of the apoptosis signal-regulating kinase 1, as its down-regulation prevented it. Finally, glucose deprivation induced cell apoptosis, which was associated with a significant increase in both caspase 3 and caspase 12 active forms. Taken together, our studies reveal a new mechanism whereby glucose deprivation can modulate AD pathogenesis by influencing tau phosphorylation and suggest that this pathway may be a new therapeutic target for AD.

  8. Increased activation of the human cerebellum during pitch discrimination: a positron emission tomography (PET) study.

    PubMed

    Petacchi, Augusto; Kaernbach, Christian; Ratnam, Rama; Bower, James M

    2011-12-01

    Recent years have seen a growing debate concerning the function of the cerebellum. Here we used a pitch discrimination task and PET to test for cerebellar involvement in the active control of sensory data acquisition. Specifically, we predicted greater cerebellar activity during active pitch discrimination compared to passive listening, with the greatest activity when pitch discrimination was most difficult. Ten healthy subjects were trained to discriminate deviant tones presented with a slightly higher pitch than a standard tone, using a Go/No Go paradigm. To ensure that discrimination performance was matched across subjects, individual psychometric curves were assessed beforehand using a two-step psychoacoustic procedure. Subjects were scanned while resting in the absence of any sounds, while passively listening to standard tones, and while detecting deviant tones slightly higher in pitch among these standard tones at four different performance levels. Consistent with our predictions, 1) passive listening alone elicited cerebellar activity (lobule IX), 2) cerebellar activity increased during pitch discrimination as compared to passive listening (crus I and II, lobules VI, VIIB, and VIIIB), and 3) this increase was correlated with the difficulty of the discrimination task (lobules V, VI, and IX). These results complement recent findings showing pitch discrimination deficits in cerebellar patients (Parsons et al., 2009) and further support a role for the cerebellum in sensory data acquisition. The data are discussed in the light of anatomical and physiological evidence functionally connecting auditory system and cerebellum.

  9. 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

  10. Increased migration of murine keratinocytes under hypoxia is mediated by induction of urokinase plasminogen activator.

    PubMed

    Daniel, Richard J; Groves, Richard W

    2002-12-01

    One of the key consequences of cutaneous wounding is the development of tissue hypoxia. Recent data have suggested that this is a potent stimulus for increased keratinocyte migration and hence re-epithelialization, although the mechanisms responsible for this remain unclear. In this study we have investigated the relationship between hypoxia, plasminogen activation, and in vitro wound healing. Exposure of keratinocyte cultures to hypoxia resulted in upregulation of urokinase plasminogen activator mRNA and a subsequent increase in urokinase plasminogen activator-mediated plasminogen activation, as determined by indirect chromogenic peptide assay and plasminogen-linked zymography. Analysis of keratinocyte wound healing in vitro confirmed enhanced wound closure in hypoxic cultures compared with normoxic cultures after 16 h. Pretreatment of normoxic and hypoxic cultures with mitomycin C and cytochalasin B indicated that in this system wound closure was due to keratinocyte migration rather than proliferation. Addition of the broad-spectrum serine proteinase inhibitor, p-aminobenzamidine, or the specific urokinase plasminogen activator inhibitors, amiloride and WX-293, significantly reduced wound closure in hypoxic cultures and abrogated the hypoxic enhancement of wound closure. These data indicate a central role for urokinase plasminogen activators in hypoxic keratinocyte migration and suggest a potential mechanism for enhanced re-epithelialization of wounds under low oxygen tensions. PMID:12485432

  11. Effects of Gradual Increases in O2 Concentration on Nodule Activity in Soybean 1

    PubMed Central

    Hunt, Stephen; King, Bryan J.; Layzell, David B.

    1989-01-01

    The objectives of this study were to determine whether attached nodules of soybean (Glycine max L. Merr.) could adjust to gradual increases in rhizosphere pO2 without nitrogenase inhibition and to determine whether the nitrogenase activity of the nodules is limited by pO2 under ambient conditions. A computer-controlled gas blending apparatus was used to produce linear increases (ramps) in pO2 around attached nodulated roots of soybean plants in an open gas exchange system. Nitrogenase activity (H2 production in N2:O2 and Ar:O2) and respiration (CO2 evolution) were monitored continuously as pO2 was ramped from 20 to 30 kilopascals over periods of 0, 5, 10, 15, and 30 minutes. The 0, 5, and 10 minute ramps caused inhibitions of nitrogenase and respiration rates followed by recoveries of these rates to their initial values within 30 minutes. Distinct oscillations in nitrogenase activity and respiration were observed during the recovery period, and the possible basis for these oscillations is discussed. The 15 and 30 minute ramps did not inhibit nitrogenase activity, suggesting that such inhibition is not a factor in the regulation of nodule diffusion resistance. During the 30 minute ramp, a stimulation of nitrogenase activity was observed, indicating that an O2-based limitation to nitrogenase activity occurs in soybean nodules under ambient conditions. PMID:16667018

  12. 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

  13. Components of the increased circulating proteolytic activity in pediatric burn patients.

    PubMed

    Neely, A N; Warden, G D; Rieman, M; Friedberg, D L; Holder, I A

    1992-12-01

    Total proteolytic activity (PA) is increased in the circulation of pediatric burn patients. The extent of the increase correlates with the percent total body surface area (TBSA) burned and is associated with increased susceptibility to fatal infection. To determine the source or sources of this PA, three factors were evaluated: (1) levels of proteinase inhibitors--antithrombin, alpha 2-antiplasmin, and alpha 1-proteinase inhibitor; (2) levels of proteinase--neutrophil elastase; and (3) activation of circulating proteolytic cascade systems as indicated by changes in levels of system components--plasminogen and prekallikrein. All assays measured functional levels of the proteins. Normal levels were determined in 25 consecutive well children who were seeing their pediatrician for checkups (14 boys, 11 girls, ranging in age from 10 months to 17 years). Twenty-five consecutive burn victims admitted to the Shriners Burns Institute, Cincinnati Unit (19 boys, six girls, aged 10 months to 17 years), with a mean full-thickness burn of 43.2% TBSA (range, 6%-87%) were studied in the first week postburn. Antithrombin, alpha 2-antiplasmin, plasminogen, and prekallikrein levels decreased (p < 0.001) postburn, whereas elastase increased (p < 0.001). We conclude that, in pediatric burn patients, decreased proteinase inhibitors, increased proteinase, and activation of circulating proteinase cascades all contribute to elevated total circulating PA postburn.

  14. 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.

  15. 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

  16. 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.

  17. Increased Asynchronous Release and Aberrant Calcium Channel Activation in Amyloid Precursor Protein Deficient Neuromuscular Synapses

    PubMed Central

    Yang, Li; Wang, Baiping; Long, Cheng; Wu, Gangyi; Zheng, Hui

    2007-01-01

    Despite the critical roles of the amyloid precursor protein (APP) in Alzheimer's disease pathogenesis, its physiological function remains poorly established. Our previous studies implicated a structural and functional activity of the APP family of proteins in the developing neuromuscular junction (NMJ). Here we performed comprehensive analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. We found that APP deletion led to reduced paired-pulse facilitation and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca2+ channels. We propose that APP modulates synaptic transmission at the NMJ by ensuring proper Ca2+ channel function. PMID:17919826

  18. 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.

  19. 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

  20. Dopamine D3 receptor deletion increases tissue plasminogen activator (tPA) activity in prefrontal cortex and hippocampus.

    PubMed

    Castorina, A; D'Amico, A G; Scuderi, S; Leggio, G M; Drago, F; D'Agata, V

    2013-10-10

    Considerable evidence indicates that dopamine (DA) influences tissue plasminogen activator (tPA)-mediated proteolytic processing of the precursor of brain-derived neurotrophic factor (proBDNF) into mature BDNF (mBDNF). However, specific roles in this process for the dopamine D3 receptor (D3R) and the underlying molecular mechanisms are yet to be fully characterized. In the present study, we hypothesized that D3R deletion could influence tPA activity in the prefrontal cortex and hippocampus. Using D3R knockout (D3(-/-)) mice, we show that receptor inactivation is associated with increased tPA expression/activity both in the prefrontal cortex and, to a greater extent, in the hippocampus. Augmented tPA expression in D3(-/-) mice correlated with increased BDNF mRNA levels, plasmin/plasminogen protein ratio and the conversion of proBDNF into mBDNF, as well as enhanced tPA and mBDNF immunoreactivity, as determined by quantitative real time polymerase chain reaction (qRT-PCR), immunoblot and immunohistochemistry. In addition, when compared to wild-type controls, D3(-/-) mice exhibited increased basal activation of the canonical cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-driven Akt/cAMP-response element-binding protein (CREB) signaling cascade, as determined by the increased Akt phosphorylation both at Thr304 and Ser473 residues, of DA and cAMP-regulated protein of 32kDa (DARPP-32) at Thr34 and a phosphorylation state-dependent inhibition of glycogen synthetase kinase-3β (GSK-3β) at Ser9, a substrate of Akt whose constitutive function impairs normal CREB transcriptional activity through phosphorylation at its Ser129 residue. Accordingly, CREB phosphorylation at Ser133 was significantly increased in D3(-/-) mice, whereas the GSK-3β-dependent phosphorylation at Ser129 was diminished. Altogether, our finding reveals that mice lacking D3Rs show enhanced tPA proteolytic activity on BDNF which may involve, at least in part, a potentiated Akt/CREB signaling

  1. Increase of carboxylesterase activity in Fasciola hepatica recovered from triclabendazole treated sheep.

    PubMed

    Scarcella, S; Miranda-Miranda, E; Cossío-Bayúgar, R; Ceballos, L; Fernandez, V; Solana, H

    2012-10-01

    In the present work, we evaluate in vivo the activity of carboxylesterase of Fasciola hepatica exposed to triclabendazole. We observed a statistically significant increase in enzyme activity at 24 and 48 h post treatment (P<0.01 and P<0.001, respectively). The zymogram of cytosolic fractions identified a protein of 170 kDa containing the carboxylesterase activity. The densitograms of the zymograms confirmed the phenomenon of enzyme induction under the experimental conditions of the assay. These results provide not only the understanding of the importance of this metabolic pathway in flukes but carboxylesterase would also be an enzyme that could participate more actively in the development of anthelmintic resistance at TCBZ.

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

    PubMed

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

    2016-02-10

    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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Pulsed Light Stimulation Increases Boundary Preference and Periodicity of Episodic Motor Activity in Drosophila melanogaster

    PubMed Central

    Qiu, Shuang; Xiao, Chengfeng; Robertson, R. Meldrum

    2016-01-01

    There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation) on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally-generated motor pattern (struggling behavior). In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS). Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild-type Canton S (CS) flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification. PMID:27684063

  8. Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain

    NASA Astrophysics Data System (ADS)

    Mintun, Mark A.; Vlassenko, Andrei G.; Rundle, Melissa M.; Raichle, Marcus E.

    2004-01-01

    The factors regulating cerebral blood flow (CBF) changes in physiological activation remain the subject of great interest and debate. Recent experimental studies suggest that an increase in cytosolic NADH mediates increased blood flow in the working brain. Lactate injection should elevate NADH levels by increasing the lactate/pyruvate ratio, which is in near equilibrium with the NADH/NAD+ ratio. We studied CBF responses to bolus lactate injection at rest and in visual stimulation by using positron-emission tomography in seven healthy volunteers. Bolus lactate injection augmented the CBF response to visual stimulation by 38-53% in regions of the visual cortex but had no effect on the resting CBF or the whole-brain CBF. These lactate-induced CBF increases correlated with elevations in plasma lactate/pyruvate ratios and in plasma lactate levels but not with plasma pyruvate levels. Our observations support the hypothesis that an increase in the NADH/NAD+ ratio activates signaling pathways to selectively increase CBF in the physiologically stimulated brain regions.

  9. Protecting cotton photosynthesis during moderate chilling at high light intensity by increasing chloroplastic antioxidant enzyme activity.

    PubMed

    Payton, P; Webb, R; Kornyeyev, D; Allen, R; Holaday, A S

    2001-12-01

    This study examined the effect of increasing chloroplastic superoxide dismutase (SOD), ascorbate peroxidase (APX), or glutathione reductase (GR) activity via plant transformation of cotton on the initial recovery of photosynthesis following exposures to 10 degrees C and high photon flux density (PFD). Growing wild-type or non-expressing segregate plants (controls) and transformants at two PFDs (600 micromol m(-2) s(-1) and full sun) resulted in a range of total antioxidant enzyme activities. Total SOD activities above that for control leaves grown in full sun did not substantially improve the recoveries of CO(2)-saturated photosynthesis, especially for stress treatments lasting more than 1 h, while elevated APX or GR activity did improve recoveries after 1-3 h of the chilling treatment. No synergistic effects were noted when the activities of more than one antioxidant enzyme were elevated in transgenic hybrids. Although these results suggest that the protection of photosynthesis can be realized by reducing either superoxide or H(2)O(2) levels, thereby reducing the possibility of hydroxyl radical formation, the situation is complicated, since elevated APX or GR activity can improve recoveries even when additional SOD activity has no effect. In conclusion, to enhance the protection of photosynthesis using stroma-targeted antioxidant enzymes, enhancing metabolism associated with H(2)O(2) is more effective than enhancing the capacity for superoxide scavenging. Although small, the improvement in the protection of photosynthetic capacity may be sufficient to improve cotton yield in temperate regions with large diurnal temperature fluctuations.

  10. Increased levels of peroxisomal active oxygen-related enzymes in copper-tolerant pea plants

    SciTech Connect

    Palma, J.M.; Gomez, M.; Yanez, J.; Del Rio, L.A.

    1987-10-01

    The effect in vivo of high nutrient levels of copper (240 micromolar) on the activity of different metalloenzymes containing Cu, Mn, Fe, and Zn, distributed in chloroplasts, peroxisomes, and mitochondria, was studied in leaves of two varieties of Pisum sativum L. plants with different sensitivity to copper. The metalloenzymes studied were: cytochrome c oxidase, Mn-superoxide dismutase (Mn-SOD) and Cu,Zn-superoxide dismutase I (Cu,Zn-SOD I), for mitochondria; catalase and Mn-SOD, for peroxisomes; and isozyme Cu,Zn-SOD II for chloroplasts. The activity of mitochondrial SOD isozymes (Mn-SOD and Cu,Zn-SOD I) was very similar in Cu-tolerant and Cu-sensitive plants, whereas cytochrome c oxidase was lower in Cu-sensitive plants. Chloroplastid Cu,Zn-SOD activity was the same in the two plant varieties. In contrast, the peroxisomal Mn-SOD activity was considerably higher in Cu-tolerant than in Cu-sensitive plants, and the activity of catalase was also increased in peroxisomes of Cu-tolerant plants. The higher activities of these peroxisomal active oxygen-related enzymes in Cu-tolerant plants suggest the involvement of reactive oxygen intermediates (O/sub 2//sup -/, OH) in the mechanism of Cu lethality, and also imply a function for peroxisomal Mn-SOD in the molecular mechanisms of plant tolerance to Cu in Pisum sativum L.

  11. Using pedometers to increase physical activity in overweight and obese women: a pilot study

    PubMed Central

    Pal, Sebely; Cheng, Cheryl; Egger, Garry; Binns, Colin; Donovan, Robert

    2009-01-01

    Background Most public health guidelines recommend that adults participate in 30 minutes of moderate intensity physical activity on most days of the week. Establishing new ways to achieve these targets in sedentary populations need to be explored. This research evaluated whether the daily use of pedometers could increase physical activity and improve health outcomes in sedentary overweight and obese women. Methods Twenty six overweight and obese middle-aged women were randomized into two groups: The control group was not able to record their steps daily, whilst the pedometer group, were asked to record the number of steps on a daily basis for 12 weeks. Results Our data showed that the pedometer group significantly increased their steps/day, by 36%, at the end of the 12 weeks, whereas the control group's physical activity levels remained unchanged. There was no significant difference in weight or body fat composition in the pedometer group compared to the control group. However, there was a significant decrease in systolic blood pressure in the pedometer group (112.8 ± 2.44 mm Hg) compared to the control group (117.3 ± 2.03 mm Hg) (p = 0.003). Conclusion In conclusion, this pilot study shows that the combination of having step goals and immediate feedback from using a pedometer was effective in increasing physical activity levels in sedentary overweight and obese women. Trial registration ACTRN12609000176268 PMID:19703317

  12. 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

  13. VASP Increases Hepatic Fatty Acid Oxidation by Activating AMPK in Mice

    PubMed Central

    Tateya, Sanshiro; Rizzo-De Leon, Norma; Handa, Priya; Cheng, Andrew M.; Morgan-Stevenson, Vicki; Ogimoto, Kayoko; Kanter, Jenny E.; Bornfeldt, Karin E.; Daum, Guenter; Clowes, Alexander W.; Chait, Alan; Kim, Francis

    2013-01-01

    Activation of AMP-activated protein kinase (AMPK) signaling reduces hepatic steatosis and hepatic insulin resistance; however, its regulatory mechanisms are not fully understood. In this study, we sought to determine whether vasodilator-stimulated phosphoprotein (VASP) signaling improves lipid metabolism in the liver and, if so, whether VASP’s effects are mediated by AMPK. We show that disruption of VASP results in significant hepatic steatosis as a result of significant impairment of fatty acid oxidation, VLDL-triglyceride (TG) secretion, and AMPK signaling. Overexpression of VASP in hepatocytes increased AMPK phosphorylation and fatty acid oxidation and reduced hepatocyte TG accumulation; however, these responses were suppressed in the presence of an AMPK inhibitor. Restoration of AMPK phosphorylation by administration of 5-aminoimidazole-4-carboxamide riboside in Vasp−/− mice reduced hepatic steatosis and normalized fatty acid oxidation and VLDL-TG secretion. Activation of VASP by the phosphodiesterase-5 inhibitor, sildenafil, in db/db mice reduced hepatic steatosis and increased phosphorylated (p-)AMPK and p-acetyl CoA carboxylase. In Vasp−/− mice, however, sildendafil treatment did not increase p-AMPK or reduce hepatic TG content. These studies identify a role of VASP to enhance hepatic fatty acid oxidation by activating AMPK and to promote VLDL-TG secretion from the liver. PMID:23349495

  14. 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

  15. Chondroitinase enhances cortical map plasticity and increases functionally active sprouting axons after brain injury.

    PubMed

    Harris, Neil G; Nogueira, Marcia S M; Verley, Derek R; Sutton, Richard L

    2013-07-15

    The beneficial effect of interventions with chondroitinase ABC enzyme to reduce axon growth-inhibitory chondroitin sulphate side chains after central nervous system injuries has been mainly attributed to enhanced axonal sprouting. After traumatic brain injury (TBI), it is unknown whether newly sprouting axons that occur as a result of interventional strategies are able to functionally contribute to existing circuitry, and it is uncertain whether maladaptive sprouting occurs to increase the well-known risk for seizure activity after TBI. Here, we show that after a controlled cortical impact injury in rats, chondroitinase infusion into injured cortex at 30 min and 3 days reduced c-Fos⁺ cell staining resulting from the injury alone at 1 week postinjury, indicating that at baseline, abnormal spontaneous activity is likely to be reduced, not increased, with this type of intervention. c-Fos⁺ cell staining elicited by neural activity from stimulation of the affected forelimb 1 week after injury was significantly enhanced by chondroitinase, indicating a widespread effect on cortical map plasticity. Underlying this map plasticity was a larger contribution of neuronal, rather than glial cells and an absence of c-Fos⁺ cells surrounded by perineuronal nets that were normally present in stimulated naïve rats. After injury, chondroitin sulfate proteoglycan digestion produced the expected increase in growth-associated protein 43-positive axons and perikarya, of which a significantly greater number were double labeled for c-Fos after intervention with chondroitinase, compared to vehicle. These data indicate that chondroitinase produces significant gains in cortical map plasticity after TBI, and that either axonal sprouting and/or changes in perineuronal nets may underlie this effect. Chondroitinase dampens, rather than increases nonspecific c-Fos activity after brain injury, and induction of axonal sprouting is not maladaptive because greater numbers are functionally

  16. Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity

    PubMed Central

    Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah

    2014-01-01

    More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1–12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n = 12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n = 39), where a subset (n = 11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P = 0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P = 0.30). Experimental tactile (P = 0.012) and noxious (P = 0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. PMID:25218826

  17. 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.

  18. 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

  19. Prompts to Disrupt Sitting Time and Increase Physical Activity at Work, 2011–2012

    PubMed Central

    Rote, Aubrianne E.; Welch, Whitney A.; Maeda, Hotaka; Hart, Teresa L.; Cho, Young Ik; Strath, Scott J.

    2014-01-01

    Introduction The objective of this study was to assess change in sitting and physical activity behavior in response to a workplace intervention to disrupt prolonged sitting time. Methods Sixty office workers were randomized to either a Stand group (n = 29), which received hourly prompts (computer-based and wrist-worn) to stand up, or a Step group (n = 31), which received the same hourly prompts and an additional prompt to walk 100 steps or more upon standing. An ActivPAL monitor was used to assess sitting and physical activity behavior on the same 3 consecutive workdays during baseline and intervention periods. Mixed-effect models with random intercepts and random slopes for time were performed to assess change between groups and across time. Results Both groups significantly reduced duration of average sitting bouts (Stand group, by 16%; Step group, by 19%) and the number of sitting bouts of 60 minutes or more (Step group, by 36%; Stand group, by 54%). The Stand group significantly reduced total sitting time (by 6.6%), duration of the longest sitting bout (by 29%), and number of sitting bouts of 30 minutes or more (by 13%) and increased the number of sit-to-stand transitions (by 15%) and standing time (by 23%). Stepping time significantly increased in the Stand (by 14%) and Step (by 29%) groups, but only the Step group significantly increased (by 35%) the number of steps per workday. Differences in changes from baseline to intervention between groups were not significant for any outcome. Conclusion Interventions that focus on disrupting sitting time only in the workplace may result in less sitting. When sitting time disruptions are paired with a physical activity prompt, people may be more likely to increase their workday physical activity, but the effect on sitting time may be attenuated. PMID:24784909

  20. Tear fluid hyperosmolality increases nerve impulse activity of cold thermoreceptor endings of the cornea.

    PubMed

    Parra, Andres; Gonzalez-Gonzalez, Omar; Gallar, Juana; Belmonte, Carlos

    2014-08-01

    Dry eye disease (DED) is a multifactorial disorder affecting the composition and volume of tears. DED causes ocular surface dryness, cooling, and hyperosmolality, leading ultimately to corneal epithelium damage and reduced visual performance. Ocular discomfort is the main clinical symptom in DED. However, the peripheral neural source of such unpleasant sensations is still unclear. We analyzed in excised, superfused mouse eyes, the effect of NaCl-induced hyperosmolality (325-1005 mOsm·kg(-1)) on corneal cold thermoreceptor and polymodal nociceptor nerve terminal impulse (NTI) activity. Osmolality elevations at basal corneal temperature (33.6°C) linearly increased the ongoing NTI frequency of cold thermoreceptors, at a mean rate of 0.34 imp·s(-1)/10 mOsm. This frequency increase became significant with osmolality values greater than 340 mOsm. Comparison of cold thermoreceptor activity increase induced by a dynamic temperature reduction of 1.8°C under iso- and hyperosmolal (360-mOsm) conditions provided evidence that more than 50% of the increased firing response was attributable to hyperosmolality. Comparatively, activation of corneal polymodal nociceptor endings by hyperosmolal solutions started with values of 600 mOsm and greater. Sensitization of polymodal nociceptors by continuous perfusion with an "inflammatory soup" (bradykinin, histamine, prostaglandin E2 [PGE2], serotonin, and adenosine triphosphate [ATP]) did not enhance their activation by hyperosmolal solutions. High osmolality also altered the firing pattern and shape of cold and polymodal NTIs, possibly reflecting disturbances in local membrane currents. Results strongly suggest that tear osmolality elevations in the range observed in DED predominantly excite cold thermoreceptors, supporting the hypothesis that dryness sensations experienced by these patients are due, at least in part, to an augmented activity of corneal cold thermoreceptors.

  1. Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase.

    PubMed

    Mathew, T S; Ferris, R K; Downs, R M; Kinsey, S T; Baumgarner, B L

    2014-10-24

    Caffeine has been shown to promote calcium-dependent activation of AMP-activated protein kinase (AMPK) and AMPK-dependent glucose and fatty acid uptake in mammalian skeletal muscle. Though caffeine has been shown to promote autophagy in various mammalian cell lines it is unclear if caffeine-induced autophagy is related to the calcium-dependent activation of AMPK. The purpose of this study was to examine the role of calcium-dependent AMPK activation in regulating caffeine-induced autophagy in mammalian skeletal muscle cells. We discovered that the addition of the AMPK inhibitor Compound C could significantly reduce the expression of the autophagy marker microtubule-associated protein 1 light chain 3b-II (LC3b-II) and autophagic vesicle accumulation in caffeine treated skeletal muscle cells. Additional experiments using pharmacological inhibitors and RNA interference (RNAi) demonstrated that the calcium/calmodulin-activated protein kinases CaMKKβ and CaMKII contributed to the AMPK-dependent expression of LC3b-II and autophagic vesicle accumulation in a caffeine dose-dependent manner. Our results indicate that in skeletal muscle cells caffeine increases autophagy by promoting the calcium-dependent activation of AMPK.

  2. 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

  3. 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

  4. Physical activity associated with increased resting-state functional connectivity in multiple sclerosis.

    PubMed

    Prakash, Ruchika Shaurya; Patterson, Beth; Janssen, Alisha; Abduljalil, Amir; Boster, Aaron

    2011-11-01

    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates.

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

    PubMed

    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; Herrero, Laura

    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

  6. 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.

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

    PubMed

    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; Bozza, Fernando A; Bozza, Patricia T

    2013-11-14

    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.

  8. 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

  9. Increase in alkaline phosphatase activity in calvaria cells cultured with diphosphonates.

    PubMed Central

    Felix, R; Fleisch, H

    1979-01-01

    1. Dichloromethanediphosphonate and to a lesser degree 1-hydroxyethane-1,1-diphosphonate, two compounds characterized by a P-C-P bond, increased the alkaline phosphatase activity of cultured rat calvaria cells up to 30 times in a dose-dependent fashion. 2. Both diphosphonates also slightly inhibited the protein synthesis in these cells. 3. Thymidine, an inhibitor of cell division, did not inhibit the induction of the enzyme, indicating that the increase in enzyme activity was not due to the formation of a specific population of cells with high alkaline phosphatase activity. 4. The effect on alkaline phosphatase was suppressed by the addition of cycloheximide, an inhibitor of protein synthesis. 5. After subculturing the stimulated cells in medium without diphosphonates, the enzyme activity fell almost to the control value. 6. Bovine parathyrin diminished the enzyme activity of the control cells and the cells treated with dichloromethanediphosphonate; however, at high concentration the effect of parathyrin was greater on the diphosphonate-treated cells than on the control cells. 7. The electrophoretic behaviour, heat inactivation, inhibition by bromotetramisole or by phenylalanine, and the Km value of the induced enzyme were identical with that of the control enzyme. PMID:534490

  10. 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

  11. 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

  12. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    PubMed Central

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  13. 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

  14. HIV-1 Tat Protein Increases Microglial Outward K+ Current and Resultant Neurotoxic Activity

    PubMed Central

    Liu, Jianuo; Xu, Peng; Collins, Cory; Liu, Han; Zhang, Jingdong; Keblesh, James P.; Xiong, Huangui

    2013-01-01

    Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders. Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain. To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein. Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-α, IL-1β, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K+ current and Kv1.3 channel expression. Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K+ channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure. Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K+ channel blocker-treated microglia. Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation. These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders. PMID:23738010

  15. 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

  16. 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

  17. 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

  18. Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia

    PubMed Central

    Harper, Angelica R.; Wang, Xiang; Moiseyev, Gennadiy; Ma, Jian-Xing; Summers, Jody A.

    2016-01-01

    Purpose Increases in retinaldehyde dehydrogenase 2 (RALDH2) transcript in the chick choroid suggest that RALDH2 may be responsible for increases observed in all-trans-retinoic acid (atRA) synthesis during recovery from myopic defocus. The purpose of the present study was to examine RALDH2 protein expression, RALDH activity, and distribution of RALDH2 cells in control and recovering chick ocular tissues. Methods Myopia was induced in White Leghorn chicks for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of RALDH isoforms in chick ocular tissues was evaluated by Western blot. Catalytic activity of RALDH was measured in choroidal cytosol fractions using an in vitro atRA synthesis assay together with HPLC quantification of synthesized atRA. Distribution of RALDH2 cells throughout the choroid was evaluated by immunohistochemistry. Results RALDH2 was expressed predominately in the chick choroid (P < 0.001) and increased after 24 hours and 4 days of recovery (76%, 74%, and 165%, respectively; P < 0.05). Activity of RALDH was detected solely in the choroid and was elevated at 3 and 7 days of recovery compared to controls (70% and 48%, respectively; P < 0.05). The number of RALDH2 immunopositive cells in recovering choroids was increased at 24 hours and 4 to 15 days of recovery (P < 0.05) and were concentrated toward the RPE side compared to controls. Conclusions The results of this study suggest that RALDH2 is the major RALDH isoform in the chick choroid and is responsible for the increased RALDH activity seen during recovery. PMID:27654415

  19. Overexpression of α-synuclein simultaneously increases glutamate NMDA receptor phosphorylation and reduces glucocerebrosidase activity.

    PubMed

    Yang, Junfeng; Hertz, Ellen; Zhang, Xiaoqun; Leinartaité, Lina; Lundius, Ebba Gregorsson; Li, Jie; Svenningsson, Per

    2016-01-12

    Progressive accumulation of α-synuclein (α-syn)-containing protein aggregates throughout the nervous system is a pathological hallmark of Parkinson's disease (PD). The mechanisms whereby α-syn exerts neurodegeneration remain to be fully understood. Here we show that overexpression of α-syn in transgenic mice leads to increased phosphorylation of glutamate NMDA receptor (NMDAR) subunits NR1 and NR2B in substantia nigra and striatum as well as reduced glucocerebrosidase (GCase) levels. Similarly, molecular studies performed in mouse N2A cells stably overexpressing human α-syn ((α-syn)N2A) showed that phosphorylation states of the same NMDAR subunits were increased, whereas GCase levels and lysosomal GCase activity were reduced. (α-syn)N2A cells showed an increased sensitivity to neurotoxicity towards 6-hydroxydopamine and NMDA. However, wildtype N2A, but not (α-syn)N2A cells, showed a further reduction in viability when co-incubated with 6-hydroxydopamine and the lysosomal inhibitors NH4Cl and leupeptin, suggesting that α-syn per se perturbs lysosomal functions. NMDA treatment reduced lysosomal GCase activity to the same extent in (α-syn)N2A cells as in wildtype N2A cells, indicating that the α-syn-dependent difference in NMDA neurotoxicity is unrelated to an altered GCase activity. Nevertheless, these data provide molecular evidence that overexpression of α-syn simultaneously induces two potential neurotoxic hits by increasing glutamate NMDA receptor phosphorylation, consistent with increased NMDA receptors functionality, and reducing GCase activity. PMID:26610904

  20. 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.

  1. Antiretroviral Treatment is Associated with Increased Attentional Load-Dependent Brain Activation in HIV Patients

    PubMed Central

    Chang, L.; Yakupov, R.; Nakama, H.; Stokes, B.; Ernst, T.

    2009-01-01

    Objective The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Methods Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n=18), HIV subjects treated with antiretroviral medications (HIV+ ARV, n=12), or not treated with antiretroviral medications (HIV+NARV, n=12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. Results HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected=0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected=0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. Interpretation These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention. PMID:18247124

  2. 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

  3. 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

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

    PubMed

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

    2004-11-26

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

  5. 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

  6. Phagocytic Activity Is Impaired in Type 2 Diabetes Mellitus and Increases after Metabolic Improvement

    PubMed Central

    Petriz, Jordi; Hernández, Cristina; Simó, Rafael

    2011-01-01

    Objective 1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels. Methods 21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry. Results Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029). Conclusions Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization. PMID:21876749

  7. 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

  8. 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.

  9. Nicotine-induced locomotor activity is increased by preexposure of rats to prenatal stress.

    PubMed

    Koehl, M; Bjijou, Y; Le Moal, M; Cador, M

    2000-11-01

    Genetic factors are believed to play a predominant role in the individual differences observed in behavioral and pharmacological responses to drugs of abuse. An increasing literature indicates, however, that epigenetic factors can be involved as well. In this report we examined whether developmental changes induced by prenatal stress could alter the way animals respond to the psychostimulant effect of nicotine when adults. The results show that nicotine induces a dose-dependent increase of locomotor activity in both groups, and that prenatally-stressed animals exhibit a higher behavioral response at all doses. This study emphasizes the importance of early environment in the later development of drug-related behavior. PMID:11056199

  10. Endolymphatic Sac Tumor Showing Increased Activity on 68Ga DOTATATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga DOTA-conjugated peptides in the workup and management of these patients. PMID:27454593

  11. 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

  12. Increased muscle activation following motor imagery during the rehabilitation of the anterior cruciate ligament.

    PubMed

    Lebon, Florent; Guillot, Aymeric; Collet, Christian

    2012-03-01

    Motor imagery (MI) is the mental representation of an action without any concomitant movement. MI has been used frequently after peripheral injuries to decrease pain and facilitate rehabilitation. However, little is known about the effects of MI on muscle activation underlying the motor recovery. This study aimed to assess the therapeutic effects of MI on the activation of lower limb muscles, as well as on the time course of functional recovery and pain after surgery of the anterior cruciate ligament (ACL). Twelve patients with a torn ACL were randomly assigned to a MI or control group, who both received a series of physiotherapy. Electromyographic activity of the quadriceps, pain, anthropometrical data, and lower limb motor ability were measured throughout a 12-session therapy. The data provided evidence that MI elicited greater muscle activation, even though imagery practice did not result in pain decrease. Muscle activation increase might originate from a redistribution of the central neuronal activity, as there was no anthropometric change in lower limb muscles after imagery practice. This study confirmed the effectiveness of integrating MI in a rehabilitation process by facilitating muscular properties recovery following motor impairment. MI may thus be considered a reliable adjunct therapy to help injured patients to recover motor functions after reconstructive surgery of ACL.

  13. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  14. 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

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

    PubMed

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

    2015-03-01

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

  16. 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

  17. 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

  18. Paliperidone increases spontaneous and evoked firing of mesocortical dopaminergic neurons by activating a hyperpolarization-activated inward current.

    PubMed

    Dong, Haiman; Wang, Qian; Zhu, Dexiao; Gao, Fei; Wang, Hui; Bao, Lihua; Zhang, Jing; Hu, Yanlai; Ding, Zhaoxi; Sun, Jinhao

    2016-10-01

    Mesocortical dopaminergic (DA) subtype neurons specifically project to the prefrontal cortex, which is closely related with schizophrenia. Mesocortical DA neurons have unique physiological characteristics that are different from those of mesostriatal and mesolimbic DA neurons. Paliperidone, an atypical antipsychotic, is currently used to treat schizophrenia and has better therapeutic effects than typical antipsychotics. However, the underlying physiological mechanism remains unclear. To explore the effects of paliperidone on mesocortical DA neuron activity, here, we retrogradely labeled these cells with fluorescent microsphere retrobeads, and the electrophysiological changes were recorded in whole-cell recordings in rat midbrain slices with or without paliperidone. The data showed that paliperidone (20μmol/L) increased the spontaneous firing rates of labeled mesocortical neurons (P<0.05). Moreover, paliperidone also increased the frequency of evoked action potentials by current injection stimulation (P<0.05), whereas the accompanying amplitude decreased. Furthermore, to explore the mechanisms of paliperidone's effect, Ih currents were detected, and the results showed that hyperpolarizing voltage pulses evoked instantaneous Ih inward currents and paliperidone increased the maximum Ih current. In addition, paliperidone decreased the spontaneous inhibitory postsynaptic currents. Thus, paliperidone increased the spontaneous and evoked firing of mesocortical neurons, possibly by activating the Ih inward current and reducing the inhibitory synaptic transmission, which provides an underlying mechanism of paliperidone's application in schizophrenia. PMID:27435059

  19. 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

  20. 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.

  1. Use of pedometers to increase physical activity among children and adolescents with chronic kidney disease

    PubMed Central

    Akber, Aalia; Portale, Anthony A.; Johansen, Kirsten L.

    2014-01-01

    Background Children and adolescents with chronic kidney disease (CKD) are inactive relative to their peers. Methods Forty-four children and adolescents aged 7-20 years with CKD, end-stage renal disease (ESRD) on dialysis or a kidney transplant participated in a12-week pedometer-based intervention to increase physical activity. Patients recorded daily step counts and reported them weekly. Pediatric Quality of Life Inventory (PedsQL) and six-minute walk (6MW) were administered at baseline and after 12 weeks. Results Age was 15.1±3.4 years; 27% had CKD, 16% were receiving dialysis, and 57% had received a kidney transplant. Mean daily step count did not change significantly (+48, 95% CI −48 to +145 steps/day per week). Transplant recipients and patients with CKD increased their activity by 100 steps/day (95% CI −14 to 208) and 73 steps/day (95% CI −115 to 262) each week, respectively, and patients on dialysis decreased by 133 steps/day (95% CI −325 to 58; p-value for interaction 0.03) in multivariable analysis. Change in physical activity was associated with change in 6MW distance (r=0.74, p<0.001) and change in physical functioning (r=0.53, p=0.001). Conclusions Youths with CKD did not significantly increase their activity over 12 weeks of a pedometer-based intervention. However, changes in physical activity were associated with changes in physical functioning and performance. PMID:24648129

  2. 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

  3. The effect of increased physical activity on pulmonary diffusing capacity in unfit women.

    PubMed

    Flaherty, Joseph M; Smoliga, James M; Zavorsky, Gerald S

    2014-03-01

    The purpose of the study was to determine whether short-term high-intensity aerobic interval training improves resting pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). Twenty-eight sedentary women [mean (SD) age 32 (11) years, body mass index 24.3 (5.7) kg m(-2)] were randomly assigned to either a self-directed moderate-intensity physical activity (n = 14) group or a supervised high-intensity aerobic interval training group (n = 14). The moderate physical activity group and the aerobic interval training group increased weekly physical activity energy expenditure by 800 and 1600 kcal week(-1), respectively. After 6 weeks, aerobic capacity increased to a similar exent in both groups (mean improvement 8%, effect size 0.39). The DLNO, but not DLCO, increased to a similar extent in both groups, by 4% or 3.0 (5.7) [95% confidence interval 0.8, 5.2] ml min(-1) mmHg(-1) m(-2) from pre- to post-training (effect size 0.27). There was no correlation between the change in aerobic capacity and the change in DLNO (P > 0.05) or between the change in aerobic capacity and the change in total weekly physical activity energy expenditure (P > 0.05). Interval training does not provide additional improvements in DLNO or aerobic capacity compared with self-directed moderate-intensity physical activity (4-6 metabolic equivalent tasks, 800 kcal week(-1), for 6 weeks) in unfit women. Despite the slight improvement in both DLNO and aerobic capacity, true meaningful physiological changes in these parameters remain questionable.

  4. 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

  5. Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

    PubMed

    Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

    2009-12-01

    Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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 24 h following neonatal alcohol exposure (postnatal days (PDs) 4-9, 5.25 g/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

  11. 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.

  12. Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

    PubMed

    Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

    2013-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

  13. 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.

  14. Increased cloud activation potential of secondary organic aerosol for atmospheric mass loadings

    NASA Astrophysics Data System (ADS)

    King, S. M.; Rosenoern, T.; Shilling, J. E.; Chen, Q.; Martin, S. 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. A sensitivity analysis suggests that a drop in surface tension must be invoked to explain quantitatively the CCN observations at low SOA particle mass loadings. Other factors, such as decreased molecular weight, increased density, or increased van't Hoff factor, can contribute to the explanation but are quantitatively insufficient as the full explanation.

  15. Pedometers and brief e-counseling: increasing physical activity for overweight adults.

    PubMed Central

    VanWormer, Jeffrey J

    2004-01-01

    Physical inactivity has emerged as a public health epidemic and is associated with the rising obesity rate. A multiple-treatments reversal design was utilized to test whether pedometer-aided self-monitoring and brief e-counseling could help 3 overweight adults increase their physical activity. Dependent measures were taken for pedometer steps and weight. Two participants approximately doubled their daily step totals and lost a modest amount of weight by study end. PMID:15529901

  16. 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

  17. 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

  18. 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

  19. The Evidence for Increased L1 Activity in the Site of Human Adult Brain Neurogenesis

    PubMed Central

    Kurnosov, Alexey A.; Ustyugova, Svetlana V.; Nazarov, Vadim I.; Minervina, Anastasia A.; Komkov, Alexander Yu.; Shugay, Mikhail; Pogorelyy, Mikhail V.; Khodosevich, Konstantin V.; Mamedov, Ilgar Z.; Lebedev, Yuri B.

    2015-01-01

    Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus—the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory. PMID:25689626

  20. Glucocorticoid hormones increase the activity of plasma membrane alkaline phosphodiesterase I in rat hepatoma cells.

    PubMed Central

    Rousseau, G G; Amar-Costesec, A; Verhaegen, M; Granner, D K

    1980-01-01

    In rat hepatoma cells the synthetic glucocorticoid dexamethasone causes a 3-fold increase in the activity of the plasma membrane enzyme alkaline phosphodiesterase I (oligonucleat 5'-nucleotidohydrolase, EC 3.1.4.1). The data are consistent with an induction phenomenon mediated by the glucocorticoid receptor involved in tyrosine aminotransferase induction. The effect on alkaline phosphodiesterase I is not a reflection of a general membrane effect of dexamethasone, because the activity of three other enzymes of the plasma membrane is unaffected. On the other hand, nucleoside diphosphatase (nucleoside diphosphate phosphohydrolase acting on ADP) activity is inhibited. Thus, two more enzymes sensitive to glucocorticoids have been identified in a cell line in which these hormones influence only very few gene products. This paper describes enzymatic changes in the plasma membrane of rat hepatoma cells in which glucocorticoids normalize a number of membrane-associated processes that are considered to be characteristic of transformed cells. PMID:6102383

  1. 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

  2. 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

  3. Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

    PubMed

    Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

    2016-09-01

    This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

  4. Activation of NMDA receptors increases proliferation and differentiation of hippocampal neural progenitor cells.

    PubMed

    Joo, Jae-Yeol; Kim, Byung-Woo; Lee, Jeong-Sik; Park, Jin-Yong; Kim, Sunoh; Yun, Young-Joo; Lee, Sang-Hun; Lee, Suk-Ho; Rhim, Hyewhon; Son, Hyeon

    2007-04-15

    The prolonged effects of N-methyl-D-aspartate (NMDA) receptor activation on the proliferation and differentiation of hippocampal neural progenitor cells (NPCs) were studied. Under conditions of mitogen-mediated proliferation, a single NMDA pulse (5 microM) increased the fraction of 5-bromo-2-deoxyuridine (BrdU)-positive (BrdU(+)) cells after a delay of 72 hours. Similarly, a single systemic injection of NMDA (100 mg/kg) increased the number of BrdU(+) cells in the dentate gyrus (DG) after 28 days, but not after 3 days. NMDA receptor activation induced an immediate influx of Ca(2+) into the NPCs and the NPCs expressed and released vascular endothelial growth factor (VEGF) in an NMDA receptor-dependent manner within 72 hours. With repetitive stimulation at the same dose, NMDA stimulated the acquisition of a neuronal phenotype accompanied by an increase in the expression of proneural basic helix-loop-helix (bHLH) factors. Together these findings suggest that neurogenesis in the developing brain is likely to be both directly and indirectly regulated by complex interactions between Ca(2+) influx and excitation-releasable cytokines, even at mild levels of excitation. In addition, our results are the first to show that stimulation of NPCs may lead to either proliferation or neuronal differentiation, depending on the level of NMDA receptor activation.

  5. Brassinolide alleviates salt stress and increases antioxidant activity of cowpea plants (Vigna sinensis).

    PubMed

    El-Mashad, Ali Abdel Aziz; Mohamed, Heba Ibrahim

    2012-07-01

    Soil salinity is one of the most severe factors limiting growth and physiological response in Vigna sinensis plants. Plant salt stress tolerance requires the activation of complex metabolic activities including antioxidative pathways, especially reactive oxygen species and scavenging systems within the cells which can contribute to continued growth under water stress. The present investigation was carried out to study the role of brassinolide in enhancing tolerance of cowpea plants to salt stress (NaCl). Treatment with 0.05 ppm brassinolide as foliar spray mitigated salt stress by inducing enzyme activities responsible for antioxidation, e.g., superoxide dismutase, peroxidase, polyphenol oxidase, and detoxification as well as by elevating contents of ascorbic acid, tocopherol, and glutathione. On the other hand, total soluble proteins decreased with increasing NaCl concentrations in comparison with control plants. However, lipid peroxidation increased with increasing concentrations of NaCl. In addition to, the high concentrations of NaCl (100 and 150 mM) decreased total phenol of cowpea plants as being compared with control plants. SDS-PAGE of protein revealed that NaCl treatments alone or in combination with 0.05 ppm brassinolide were associated with the disappearance of some bands or appearance of unique ones in cowpea plants. Electrophoretic studies of α-esterase, β-esterase, polyphenol oxidase, peroxidase, acid phosphatase, and superoxide dismutase isoenzymes showed wide variations in their intensities and densities among all treatments.

  6. Muscle activity patterns during quick increase of movement amplitude in rapid elbow extensions.

    PubMed

    Takatoku, Nozomi; Fujiwara, Motoko

    2010-04-01

    In this study, we investigated a motor strategy for increasing the amplitude of movement in rapid extensions at the elbow joint. This study focused on the changes in a triphasic electromyographic (EMG) pattern, i.e., the first agonist burst (AG1), the second agonist burst (AG2) and the antagonist burst (ANT), for increasing the amplitude of movement required after the initiation of movement. Subjects performed 40 degrees (Basic task) and 80 degrees of extension (Wide task). These tasks were performed under two conditions; performing a predetermined task (SF condition) and performing a task in response to a visual stimulus immediately after movement commencement (ST condition). Kinematic parameters and EMG activity from the agonist (triceps brachii) and the antagonist (biceps brachii) muscles were recorded. As a result, the onset latency of AG1 and AG2 and the duration of AG1 were longer under the ST condition than the SF condition. No difference was observed between the SF and ST condition with respect to ANT activity. It is concluded that the motor strategy for increasing the amplitude of movement after the initiation of movement was to control the movement velocity and the timing to stop movement by the coactivation duration of AG1 and ANT and to stop the desired position accurately by AG2 activity.

  7. 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

  8. 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

  9. 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.

  10. [Dietary and physical activity factors as determinants of the increase in overweight/obesity in Brazil].

    PubMed

    Mendonça, Cristina Pinheiro; dos Anjos, Luiz Antonio

    2004-01-01

    Data from Brazilian national surveys conducted since the 1970s have indicated an increase in the prevalence of overweight/obesity. The two most frequently cited causes of this trend have been dietary changes and reduction in physical activity, characterizing a "contemporary Western lifestyle". The objective of this paper is to identify and assess some indicators associated with changes in eating habits and physical activity patterns in the Brazilian population in the last 30 years. Despite the lack of detailed data, the following factors appear to play an important role in the process: internal migration; dining out; increased consumption of fast food; labor changes; transportation; and the use of home appliances. More information on dietary and physical activity patterns in association with anthropometric data on the Brazilian population are needed for a better understanding of each factor's role in these relationships. Meanwhile, inter-sector programs and projects with well-defined targets and outcomes are needed for the population's adherence to a healthier lifestyle, in order to control the increase in overweight/obesity. PMID:15263980

  11. Increased error-related thalamic activity during early compared to late cocaine abstinence

    PubMed Central

    Li, Chiang-shan R.; Luo, Xi; Sinha, Rajita; Rounsaville, Bruce J.; Carroll, Kathleen M.; Malison, Robert T.; Ding, Yu-Shin; Zhang, Sheng; Ide, Jaime S.

    2010-01-01

    Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control. PMID:20163923

  12. Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI)

    PubMed Central

    Westfall, Daniel R.; West, John D.; Bailey, Jessica N.; Arnold, Todd W.; Kersey, Patrick A.; Saykin, Andrew J.; McDonald, Brenna C.

    2016-01-01

    Purpose The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. Methods Nineteen adolescents (mean age 14.7 years) who experienced mTBI 3–12 months previously (mean 7.5 months) and 19 matched healthy controls (mean age 14.0 years) completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. Results No between-group differences were found for cognition, behavior, or N-back task performance, though the expected decreased accuracy and increased reaction time as task difficulty increased were apparent. However, the mTBI group showed significantly greater brain activation than controls during the most difficult working memory task condition. Conclusion Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of natural recovery, which could have important clinical implications. PMID:26684070

  13. 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.

  14. 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

  15. 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

  16. Permeability-increasing activity in hereditary angioneurotic edema plasma. II. Mechanism of formation and partial characterization.

    PubMed

    Donaldson, V H; Ratnoff, O D; Dias Da Silva, W; Rosen, F S

    1969-04-01

    Plasma from persons with hereditary angioneurotic edema readily developed the capacity to increase vascular permeability and to induce the isolated rat uterus to contract. Both activities resided in a small, heat-stable molecule that was apparently a polypeptide. Crude preparations of the polypeptide were inactivated during incubation with trypsin. They also failed to produce pain and erythema, but caused markedly increased vascular permeability in human skin. These characteristics differ from those of bradykinin, from which crude preparations of the polypeptide could also be distinguished by electrophoretic mobility and paper chromatographic behavior. Proof that the polypeptide is truly different from bradykinin must await its further purification. Histamine played no role in the activities observed. Although the enzymes functioning to release the permeability factor and kinin activities in hereditary angioneurotic edema plasma were not clearly defined, one or more plasma enzymes other than C'1 esterase presumably participated either in conjunction with C'1 esterase or in pari passu events to release the polypeptide mediating these activities. PMID:5813121

  17. Evidence for increased peroxidative activity in muscles from streptozotocin-diabetic rats

    SciTech Connect

    Lammi-Keefe, C.J.; Swan, P.B.; Hegarty, P.V.J.

    1984-05-01

    The ability of cardiac and skeletal muscles from diabetic rats to metabolize superoxide and hydrogen peroxide was determined by the activities of superoxide dismutase (SOD) and catalase, respectively. Male and female Sprague-Dawley rats, 43 days old, were made diabetic with a single intravenous injection of streptozotocin (70 mg/kg body weight). On the 80th day after injection the blood glucose concentration of these rats was increased fourfold, and the plasma insulin concentration was decreased four- to fivefold compared to controls. Body weights of male diabetic rats were 61% and those of female diabetic rats were 66% of their ad libitum-fed controls. The seven different skeletal muscles examined weighed less in the diabetic rats than in controls of the same age and body weight. Comparison to the body weight controls allowed the distinction of specific effects due to lack of insulin from effects due to retardation in muscle growth. Increased catalase activity in all muscles examined from diabetic rats (plantaris, gastrocnemius, and heart) suggested a response in catalase activity similar to that of starved rats. SOD activity was not altered in the diabetic rat skeletal muscles and erythrocytes, but was somewhat decreased in the heart.

  18. Prolonged CD154 Expression on Pediatric Lupus CD4 T Cells Correlates with Increased CD154 Transcription, Increased NFAT Activity, and Glomerulonephritis

    PubMed Central

    Mehta, Jay; Genin, Anna; Brunner, Michael; Scalzi, Lisabeth V; Mishra, Nilamadhab; Beukelman, Timothy; Cron, Randy Q

    2010-01-01

    Objective To assess CD154 expression in pediatric lupus and explore a transcriptional mechanism explaining dysregulated CD154 expression. Methods Cell surface CD154 expression was examined, pre- and post-activation, on peripheral blood CD4 T cells from 29 children with lupus and matched controls by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on lupus CD4 T cells was correlated with CD154 message and transcription rates by real-time RT-PCR and nuclear run-on assays, respectively. NFAT transcriptional activity and NFAT mRNA levels in lupus CD4 T cells were explored by reporter gene analysis and real-time RT-PCR, respectively. Results CD154 surface protein levels were increased 1.44-fold on lupus CD4 T cells compared to controls at one day post-activation ex vivo. This increase correlated clinically with the presence of nephritis and elevated erythrocyte sedimentation rate. Increased CD154 protein also correlated with increased CD154 mRNA levels and rates of CD154 transcription, particularly at later time-points post-T cell activation. Reporter gene analyses revealed a trend for increased NFAT, but decreased AP-1 and similar NFκB, activity in lupus CD4 T cell compared to controls. Moreover, NFAT1 and, in particular, NFAT2 mRNA levels were notably increased in lupus CD4 T cells compared to controls. Conclusion Following activation, cell surface CD154 is increased on pediatric lupus CD4 T cells compared to controls, and this correlates with the presence of nephritis, increased CD154 transcription rates, and NFAT activity. These results suggest that NFAT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in treating lupus nephritis. PMID:20506525

  19. 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.

  20. 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

  1. Intranasal dopamine application increases dopaminergic activity in the neostriatum and nucleus accumbens and enhances motor activity in the open field.

    PubMed

    de Souza Silva, M A; Topic, B; Huston, J P; Mattern, C

    2008-03-01

    Dopamine (DA) plays an important role in a number of behavioral processes and neurological disorders. The intranasal administration of DA provides improved brain penetrability in comparison to systemic administration. We investigated the effects of intranasal administration of DA on the activity of dopaminergic neurons of the mesostriatal and mesolimbic systems and on motor activity. Rats previously implanted with guide-cannulae in the neostriatum (NS) and nucleus accumbens (NAc) were submitted to microdialysis procedure under urethane anesthesia. Vehicle or DA (0.03, 0.3, or 3.0 mg/kg) was administered bilaterally into the nostrils. In a separate study, animals received an intraperitoneal (i.p.) injection of vehicle or DA (0.03, 0.3, 3.0, or 30.0 mg/kg). Samples were collected every 10 min and analyzed for the content of DA and metabolites using high-performance liquid chromatography. For the open field study, rats were given intranasal vehicle or DA (0.03, 0.3, or 3.0 mg/kg) and placed into the field for 30 min. Motor activity (locomotion and rearing) and grooming were analyzed in blocks of 10 min using Ethovision. Intranasal DA (3.0 mg/kg) significantly increased DA levels in the NS and NAc immediately after administration. A comparable effect was obtained only after i.p. administration of 30 mg/kg DA. In the open field, the 3.0 mg/kg dose significantly decreased grooming behavior in the second 10 min interval and significantly increased locomotor activity in the third 10 min interval. The data indicate that intranasal administration of DA can influence dopaminergic functions and motor activity, and has a potential application in the therapy of diseases affecting the dopaminergic system.

  2. Oxidative stress increases hepatocyte iNOS gene transcription and promoter activity.

    PubMed

    Kuo, P C; Abe, K Y; Schroeder, R A

    1997-05-19

    Hepatocyte expression of inducible nitric oxide synthase (iNOS) is initiated by the presence of pro-inflammatory cytokines, such as interleukin-1beta (IL-1). In the presence of oxidative stress, IL-1beta mediated hepatocyte iNOS expression and NO synthesis are significantly increased. To determine the underlying molecular mechanism responsible for oxidative stress augmentation of hepatocyte iNOS expression, rat hepatocytes in primary culture were stimulated with IL-1beta (250 U/mL) in the presence and absence of benzenetriol (BZT, 0-100 microM), an autocatalytic source of superoxide at physiologic pH. Nuclear runon analysis demonstrated that BZT was associated with increased iNOS gene transcription in the setting of IL-1 stimulation. Transient transfection of a plasmid construct composed of the rat hepatocyte iNOS promoter and a chloramphenicol transferase reporter gene demonstrated that the combination of BZT and IL-1 significantly increased iNOS promoter activity in comparison to that of IL-1beta alone. These data indicate that BZT-mediated oxidative stress increases IL-1beta induced iNOS gene transcription and iNOS promoter activity.

  3. Improvement of Processing Speed in Executive Function Immediately following an Increase in Cardiovascular Activity

    PubMed Central

    Tam, Nicoladie D.

    2013-01-01

    This study aims to identify the acute effects of physical exercise on specific cognitive functions immediately following an increase in cardiovascular activity. Stair-climbing exercise is used to increase the cardiovascular output of human subjects. The color-naming Stroop Test was used to identify the cognitive improvements in executive function with respect to processing speed and error rate. The study compared the Stroop results before and immediately after exercise and before and after nonexercise, as a control. The results show that there is a significant increase in processing speed and a reduction in errors immediately after less than 30 min of aerobic exercise. The improvements are greater for the incongruent than for the congruent color tests. This suggests that physical exercise induces a better performance in a task that requires resolving conflict (or interference) than a task that does not. There is no significant improvement for the nonexercise control trials. This demonstrates that an increase in cardiovascular activity has significant acute effects on improving the executive function that requires conflict resolution (for the incongruent color tests) immediately following aerobic exercise more than similar executive functions that do not require conflict resolution or involve the attention-inhibition process (for the congruent color tests). PMID:24187613

  4. 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.

  5. 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.…

  6. 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

  7. 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

  8. Warming and increased precipitation have differential effects on soil extracellular enzyme activities in a temperate grassland.

    PubMed

    Zhou, Xiaoqi; Chen, Chengrong; Wang, Yanfen; Xu, Zhihong; Han, Hongyan; Li, Linghao; Wan, Shiqiang

    2013-02-01

    Few studies have conducted the responses of soil extracellular enzyme activities (EEA) to climate change, especially over the long term. In this study, we investigated the six-year responses of soil EEA to warming and increased precipitation in a temperate grassland of northern China at two depths of 0-10 and 10-20 cm. These extracellular enzymes included carbon-acquisition enzymes (β-glucosidase, BG), nitrogen-acquisition enzymes (N-acetylglucosaminidase, NAG; Leucine aminopeptidase, LAP) and phosphorus-acquisition enzymes (acid and alkaline phosphatases). The results showed that warming significantly increased acid phosphatase at the 0-10 cm depth and NAG at the 10-20 cm depth, but dramatically decreased BG and acid phosphatase in the subsurface. In contrast, increased precipitation significantly increased NAG, LAP and alkaline phosphatase in the surface and NAG, LAP and acid phosphatase in the subsurface. There was a significant warming and increased precipitation interaction on BG in the subsurface. Redundancy analysis indicated that the patterns of EEA were mainly driven by soil pH and NH(4)(+)-N and NO(3)(-)-N in the surface, while by NH(4)(+)-N and microbial biomass in the subsurface. Our results suggested that soil EEA responded differentially to warming and increased precipitation at two depths in this region, which may have implications for carbon and nutrient cycling under climate change.

  9. 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

  10. Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis.

    PubMed

    Farese, R V; Konda, T S; Davis, J S; Standaert, M L; Pollet, R J; Cooper, D R

    1987-05-01

    The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances.

  11. 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.

  12. 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

    2014-03-03

    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.

  13. The QTL GNP1 Encodes GA20ox1, Which Increases Grain Number and Yield by Increasing Cytokinin Activity in Rice Panicle Meristems

    PubMed Central

    Mi, Xue-Fei; Shan, Jun-Xiang; Xu, Jian-Long

    2016-01-01

    Cytokinins and gibberellins (GAs) play antagonistic roles in regulating reproductive meristem activity. Cytokinins have positive effects on meristem activity and maintenance. During inflorescence meristem development, cytokinin biosynthesis is activated via a KNOX-mediated pathway. Increased cytokinin activity leads to higher grain number, whereas GAs negatively affect meristem activity. The GA biosynthesis genes GA20oxs are negatively regulated by KNOX proteins. KNOX proteins function as modulators, balancing cytokinin and GA activity in the meristem. However, little is known about the crosstalk among cytokinin and GA regulators together with KNOX proteins and how KNOX-mediated dynamic balancing of hormonal activity functions. Through map-based cloning of QTLs, we cloned a GA biosynthesis gene, Grain Number per Panicle1 (GNP1), which encodes rice GA20ox1. The grain number and yield of NIL-GNP1TQ were significantly higher than those of isogenic control (Lemont). Sequence variations in its promoter region increased the levels of GNP1 transcripts, which were enriched in the apical regions of inflorescence meristems in NIL-GNP1TQ. We propose that cytokinin activity increased due to a KNOX-mediated transcriptional feedback loop resulting from the higher GNP1 transcript levels, in turn leading to increased expression of the GA catabolism genes GA2oxs and reduced GA1 and GA3 accumulation. This rebalancing process increased cytokinin activity, thereby increasing grain number and grain yield in rice. These findings uncover important, novel roles of GAs in rice florescence meristem development and provide new insights into the crosstalk between cytokinin and GA underlying development process. PMID:27764111

  14. Development and Usability Testing of an Internet Intervention to Increase Physical Activity in Overweight Adolescents

    PubMed Central

    Løndal, Knut; Ommundsen, Yngvar; Sundar, Turid; Helseth, Sølvi

    2013-01-01

    Background Internet interventions may provide opportunities for low threshold counseling using feedback to guide and support health behavior, including increased physical activity. Research shows that overweight and obese adolescents are less physically active than their peers of normal weight. There are good reasons to believe that Internet-based interventions may be particularly suitable for motivating adolescents to increase physical activity, but we need to gain further knowledge of what features are effective and how to design such interventions. Objective To describe the process of development and evaluation of usability of a Web-based program for increasing physical activity in overweight adolescents. Methods Informed by the self-determination theory, motivational interviewing, and perspectives on self-regulation, this intervention was developed in a stepwise process by an interdisciplinary team of researchers, designers, developers, and representatives from the target group. An iterative qualitative usability testing approach (observation, survey, and interview) was applied in 2 sequences, first in the lab and second in the field, to assess how adolescents (aged 12-16 years) used and experienced the program and to make adjustments to the program based on evaluation of their response. Results The following components were included in the program: self-monitoring through planning and registration of physical activity and graphical response on progress, autonomy supportive individual Web-based counseling, forum for social support, and relevant age-adjusted information about physical activity. The first usability test resulted in adjustments related mainly to making the content and aim of the different features more visible and explicit. The second test evaluated the program with adjustments from the first test, revealing that the program was well accepted by the participants and only small aesthetic adjustments had to be made to complete the final version of

  15. 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

  16. 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

  17. Grape Polyphenols Increase the Activity of HDL Enzymes in Old and Obese Rats

    PubMed Central

    Zagayko, Andriy L.; Kravchenko, Ganna B.; Krasilnikova, Oksana A.; Ogai, Yuri O.

    2013-01-01

    HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from “Enoant” obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG) levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON) and lecithin:cholesterol acyltransferase (LCAT) activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP) activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After “Enoant” administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats. PMID:23936611

  18. Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity.

    PubMed

    Jensen-Otsu, Elsbeth; Austin, Gregory L

    2015-11-01

    Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09-2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use. PMID:26610562

  19. Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity.

    PubMed

    Jensen-Otsu, Elsbeth; Austin, Gregory L

    2015-11-20

    Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09-2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.

  20. Actively using clopidogrel correlates with an increased risk of acute pancreatitis in Taiwan.

    PubMed

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

    2015-03-15

    The aim of this study is to assess whether there is an association between clopidogrel use and risk of acute pancreatitis in Taiwan. We conducted a case-control study using the database of the Taiwan National Health Insurance Program from 2000 to 2011. There were 5644 subjects aged 20-84 years with a first-time attack of acute pancreatitis as the case group and 22,576 randomly selected sex-matched and age-matched subjects without acute pancreatitis as the control group. We defined clopidogrel use as "actively using" if the final clopidogrel prescription was filled between 0 and 7 days before the date of diagnosing acute pancreatitis, or "not actively using" if the final clopidogrel prescription was filled ≧ 8 days before the date of diagnosing acute pancreatitis. Subjects who never used clopidogrel were defined as never used. The multivariable logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute pancreatitis associated with clopidogrel use. Comparing the subjects actively using clopidogrel to those who never used clopidogrel, the adjusted OR of acute pancreatitis was 8.46 (95%CI 5.25, 13.7). The adjusted OR decreased to 1.16 among subjects not actively using clopidogrel (95%CI 0.95, 1.43). Persons actively using clopidogrel are at an increased risk of acute pancreatitis. Further studies are necessary to prove the causal relationship.

  1. Grape polyphenols increase the activity of HDL enzymes in old and obese rats.

    PubMed

    Zagayko, Andriy L; Kravchenko, Ganna B; Krasilnikova, Oksana A; Ogai, Yuri O

    2013-01-01

    HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from "Enoant" obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG) levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON) and lecithin:cholesterol acyltransferase (LCAT) activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP) activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After "Enoant" administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats. PMID:23936611

  2. Increased production of penicillin-binding protein 2, increased detection of other penicillin-binding proteins, and decreased coagulase activity associated with glycopeptide resistance in Staphylococcus aureus.

    PubMed Central

    Moreira, B; Boyle-Vavra, S; deJonge, B L; Daum, R S

    1997-01-01

    The mechanism of glycopeptide resistance in the genus Staphylococcus is unknown. Since these antimicrobial compounds act by binding the peptidoglycan precursor terminus, the target of transglycosylase and transpeptidase enzymes, it was hypothesized that resistance might be mediated in Staphylococcus aureus by increased production or activity of these enzymes, commonly called penicillin-binding proteins (PBPs). To evaluate this possibility, glycopeptide-resistant mutants were prepared by passage of several clinical isolates of this species in nutrient broth containing successively increasing concentrations of the glycopeptide vancomycin or teicoplanin. Decreased coagulase activity and increased resistance to lysostaphin were uniformly present in the vancomycin-resistant mutants. Peptidoglycan cross-linking increased in one resistant isolate and decreased in two resistant isolates. The amounts of radioactive penicillin that bound to each PBP in susceptible and resistant strains were compared; PBP2 production was also evaluated by Western blotting. Increased penicillin labeling and production of PBP2 were found in all resistant derivatives selected by either vancomycin or teicoplanin. Moreover, the increase in PBP2 penicillin labeling occurred early in a series of vancomycin-selected derivatives and was strongly correlated (r > 0.9) with the increase in vancomycin and teicoplanin MIC. An increase in penicillin labeling also occurred, variably, in PBP1, PBP3, and/or PBP4. These data demonstrate a strong correlation between resistance to glycopeptides and increased PBP activity and/or production in S. aureus. Such an increase could allow PBPs to better compete with glycopeptides for the peptidoglycan precursor. PMID:9257762

  3. Triglyceride concentration and waist circumference influence alcohol-related plasminogen activator inhibitor-1 activity increase in black South Africans.

    PubMed

    Pieters, Marlien; de Lange, Zelda; Hoekstra, Tiny; Ellis, Suria M; Kruger, Annamarie

    2010-12-01

    We investigated the association between alcohol consumption and plasminogen activator inhibitor-1 activity (PAI-1act) and fibrinogen concentration in a black South African population presenting with lower PAI-1act and higher fibrinogen than what is typically observed in white populations. We, furthermore, wanted to investigate the effect of urbanization, sex, central obesity, increased triglycerides, 4G/5G polymorphism (PAI-1 only) and BMI on the association of alcohol with PAI-1act and fibrinogen. Data from 2010 apparently healthy, randomly collected black South African volunteers from the Prospective Urban and Rural Epidemiological (PURE) study were cross-sectionally analyzed. Alcohol consumption was recorded using quantitative food frequency questionnaires and fasting blood samples were collected for biochemical analysis including PAI-1act and fibrinogen. Heavy alcohol consumption is associated with significantly increased PAI-1act, in the total population as well as in the women separately, and tended to be so in men. This alcohol-related PAI-1act increase was observed in volunteers with increased triglycerides and central obesity but not in volunteers with normal levels and waist circumference. Urbanization, the 4G/5G polymorphism and BMI did not affect the association of alcohol with PAI-1act. Moderate alcohol consumption is associated with decreased fibrinogen concentration. Sex and level of urbanization did not affect the association of alcohol with fibrinogen. Fibrinogen decreased in normal and overweight volunteers but not in obese and centrally obese volunteers following moderate alcohol consumption. Triglyceride levels and waist circumference influence alcohol-related PAI-1act increase potentially through modulating adipocyte and triglyceride-induced PAI-1 production. Obesity prevented alcohol-related fibrinogen decrease possibly by counteracting the anti-inflammatory effect of moderate alcohol consumption.

  4. 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

  5. Increased brain cortical activity during parabolic flights has no influence on a motor tracking task.

    PubMed

    Schneider, Stefan; Brümmer, Vera; Mierau, Andreas; Carnahan, Heather; Dubrowski, Adam; Strüder, Heiko K

    2008-03-01

    Previous studies showed that changing forces of gravity as they typically occur during parabolic flights might be responsible for adaptional processes of the CNS. However, until now it has not been differentiated between primary influences of weightlessness and secondary influences due to psycho-physiological factors (e.g., physical or mental strain). With the aim of detecting parabolic flight related changes in central cortical activity, a resting EEG was deduced in 16 subjects before, during and after parabolic flights. After subdividing EEG into alpha-, beta-,delta- and theta-wave bands, an increase in beta-power was noticeable inflight, whereas alpha(1)-power was increased postflight. No changes could be observed for the control group. To control possible effects of cortical activation, a manual tracking task with mirror inversion was performed during either the phase of weightlessness or during the normal gravity phase of a parabolic flight. No differences in performance nor in adaptation could be observed between both groups. A third group, performing under normal and stress-free conditions in a lab showed similar tracking values. We assume that the specific increase in brain activity is a sign of an increase in arousal inflight. This does support previous assumptions of non-specific stressors during parabolic flights and has to be considered as a relevant factor for experiments on central nerve adaptation. Although no influences of stress and/or weightlessness on motor performance and adaptation could be observed, we suggest that an "inflight" control group seems to be more adequate than a laboratory control group to investigate gravity-dependent changes in motor control.

  6. Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals

    PubMed Central

    van Rooij, Sanne J. H.; Stevens, Jennifer S.; Ely, Timothy D.; Fani, Negar; Smith, Alicia K.; Kerley, Kimberly A.; Lori, Adriana; Ressler, Kerry J.; Jovanovic, Tanja

    2016-01-01

    Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes. PMID:27683563

  7. Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals.

    PubMed

    van Rooij, Sanne J H; Stevens, Jennifer S; Ely, Timothy D; Fani, Negar; Smith, Alicia K; Kerley, Kimberly A; Lori, Adriana; Ressler, Kerry J; Jovanovic, Tanja

    2016-01-01

    Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.

  8. Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals.

    PubMed

    van Rooij, Sanne J H; Stevens, Jennifer S; Ely, Timothy D; Fani, Negar; Smith, Alicia K; Kerley, Kimberly A; Lori, Adriana; Ressler, Kerry J; Jovanovic, Tanja

    2016-01-01

    Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes. PMID:27683563

  9. Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals

    PubMed Central

    van Rooij, Sanne J. H.; Stevens, Jennifer S.; Ely, Timothy D.; Fani, Negar; Smith, Alicia K.; Kerley, Kimberly A.; Lori, Adriana; Ressler, Kerry J.; Jovanovic, Tanja

    2016-01-01

    Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Activation in the VTA and Nucleus Accumbens Increases in Anticipation of Both Gains and Losses

    PubMed Central

    Carter, R. McKell; MacInnes, Jeff J.; Huettel, Scott A.; Adcock, R. Alison

    2009-01-01

    To represent value for learning and decision making, the brain must encode information about both the motivational relevance and affective valence of anticipated outcomes. The nucleus accumbens (NAcc) and ventral tegmental area (VTA) are thought to play key roles in representing these and other aspects of valuation. Here, we manipulated the valence (i.e., monetary gain or loss) and personal relevance (i.e., self-directed or charity-directed) of anticipated outcomes within a variant of the monetary incentive delay task. We scanned young-adult participants using functional magnetic resonance imaging (fMRI), utilizing imaging parameters targeted for the NAcc and VTA. For both self-directed and charity-directed trials, activation in the NAcc and VTA increased to anticipated gains, as predicted by prior work, but also increased to anticipated losses. Moreover, the magnitude of responses in both regions was positively correlated for gains and losses, across participants, while an independent reward-sensitivity covariate predicted the relative difference between and gain- and loss-related activation on self-directed trials. These results are inconsistent with the interpretation that these regions reflect anticipation of only positive-valence events. Instead, they indicate that anticipatory activation in reward-related regions largely reflects the motivational relevance of an upcoming event. PMID:19753142

  20. [Novel compounds increasing chaperone Hsp70 expression and their biological activity].

    PubMed

    Eremenko, E M; Antimonova, O I; Shekalova, O G; Polonik, S G; Margulis, B A; Guzhova, I V

    2010-01-01

    Hsp70 possesses chaperonic activity, the property associated with the protective function that was demonstrated in experiments on a great number of cell and animal models. Therefore, it seems important to search for the substances able to innocuously elevate the chaperone concentration in an organism cells and tissues. In our work, we screened of more that 60 compounds and found two chemicals, derivatives of shikonin and echinochrome that able to increase the chaperone level in a variety of human cells. It was shown that in human erythroleukemia K562 cells treated with the both substances concomitantly with elevation of Hsp70 level the absolute chaperonic activity was also increased; this can indicate mobilization of the whole cellular chaperonic machinery by above mentioned compounds. Estimating biological activity of the two substances, we demonstrated that treatments of cells by them prior to hard heat stress, hydrogen peroxide or staurosporine reduced cell mortality by 20-50 % depending on a cytotoxic factor. The results show that after simple chemical modifications these compounds might be taken as a basis of pharmaceuticals for therapy of wide range of disorders.

  1. Increased oxidative stress in pemphigus vulgaris is related to disease activity and HLA-association.

    PubMed

    Shah, Amit Aakash; Dey-Rao, Rama; Seiffert-Sinha, Kristina; Sinha, Animesh A

    2016-06-01

    Pemphigus vulgaris (PV) is a rare blistering skin disorder characterized by the disadhesion of keratinocytes due to autoantibody attack against epidermal targets including desmoglein (Dsg) 3, Dsg 1 and possibly other adhesion and non-adhesion molecules. The mechanisms leading to immune-mediated pathology in PV are multifactorial and not fully understood. Recently, oxidative stress (antioxidant/oxidant disequilibrium) has been proposed as a contributory mechanism of autoimmune skin diseases, including PV. In this study, we directly assessed oxidative stress via measurement of total antioxidant capacity (TAC) using ELISA in 47 PV patients, 25 healthy controls and 18 bullous pemphigoid (BP) patients. We also performed microarray gene expression analysis on a separate set of 21 PV patients and 10 healthy controls to evaluate transcriptional dysregulation in oxidative stress-related pathways. Our data indicate that there is a significant reduction in TAC levels in PV patients compared with healthy controls, as well as BP patients. Furthermore, PV patients with active disease have significantly lower TAC levels than PV patients in remission. We also find that HLA allele status has a significant influence on oxidative stress. These findings are corroborated by microarray analysis showing differentially expressed genes involved in oxidative stress between the aforementioned groups. Collectively, our findings provide support for a role of oxidative stress in PV. Whether increased oxidative stress leads to disease manifestation and/or activity, or if disease activity leads to increased oxidative stress remains unknown. Future longitudinal studies may help to further elucidate the relationship between PV and oxidative stress.

  2. 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

  3. Intracellular Modulation, Extracellular Disposal and Serum Increase of MiR-150 Mark Lymphocyte Activation

    PubMed Central

    de Candia, Paola; Torri, Anna; Gorletta, Tatiana; Fedeli, Maya; Bulgheroni, Elisabetta; Cheroni, Cristina; Marabita, Francesco; Crosti, Mariacristina; Moro, Monica; Pariani, Elena; Romanò, Luisa; Esposito, Susanna; Mosca, Fabio; Rossetti, Grazisa; Rossi, Riccardo L.; Geginat, Jens; Casorati, Giulia; Dellabona, Paolo; Pagani, Massimiliano; Abrignani, Sergio

    2013-01-01

    Activated lymphocytes release nano-sized vesicles (exosomes) containing microRNAs that can be monitored in the bloodstream. We asked whether elicitation of immune responses is followed by release of lymphocyte-specific microRNAs. We found that, upon activation in vitro, human and mouse lymphocytes down-modulate intracellular miR-150 and accumulate it in exosomes. In vivo, miR-150 levels increased significantly in serum of humans immunized with flu vaccines and in mice immunized with ovalbumin, and this increase correlated with elevation of antibody titers. Immunization of immune-deficient mice, lacking MHCII, resulted neither in antibody production nor in elevation of circulating miR-150. This study provides proof of concept that serum microRNAs can be detected, with minimally invasive procedure, as biomarkers of vaccination and more in general of adaptive immune responses. Furthermore, the prompt reduction of intracellular level of miR-150, a key regulator of mRNAs critical for lymphocyte differentiation and functions, linked to its release in the external milieu suggests that the selective extracellular disposal of microRNAs can be a rapid way to regulate gene expression during lymphocyte activation. PMID:24205408

  4. 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.

  5. Increased sleep spindle activity in patients with Costello syndrome (HRAS gene mutation).

    PubMed

    Della Marca, Giacomo; Leoni, Chiara; Dittoni, Serena; Battaglia, Domenica; Losurdo, Anna; Testani, Elisa; Colicchio, Salvatore; Gnoni, Valentina; Gambardella, Maria L; Mariotti, Paolo; Alfieri, Paolo; Tartaglia, Marco; Zampino, Giuseppe

    2011-06-01

    Costello syndrome is a congenital disorder because of HRAS gene mutation, frequently associated with neurologic impairment and sleep disorders. The aims of the study were to evaluate the sleep EEG, and particularly the sleep spindles, in a population of patients with Costello syndrome and to compare them with those characterizing unaffected subjects. Eleven subjects (5 men and 6 women) with Costello syndrome were included in the study; age ranged between 18 months and 31 years (mean, 9.6 ± 9.4 years). The diagnosis was posed on the basis of established clinical criteria and confirmed molecularly. Sleep EEG was studied by means of full-night, laboratory-based video-polysomnography, performed overnight, during hospitalization. Sleep activity was quantified by means of power spectral analysis. Patients heterozygous for an HRAS mutation exhibited increased EEG power in 12- to 15-Hz activity band compared with age-matched control subjects. In conclusion, the authors observed a consistent increase in the amplitude of cortical sleep spindles in all our subjects with an HRAS mutation. These "giant" spindles were not associated with any evidence of structural damage of the cortex or the thalami and should be considered as phenotypic feature of sleep EEG activity in Costello syndrome because of HRAS mutation.

  6. Increased anterior cingulate cortex and hippocampus activation in Complex PTSD during encoding of negative words.

    PubMed

    Thomaes, Kathleen; Dorrepaal, Ethy; Draijer, Nel; de Ruiter, Michiel B; Elzinga, Bernet M; Sjoerds, Zsuzsika; van Balkom, Anton J; Smit, Johannes H; Veltman, Dick J

    2013-02-01

    Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients--compared to controls--encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.

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

    PubMed

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

    1995-03-01

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

  8. Increased cerebral activity suppresses baroreflex control of heart rate in freely moving mice.

    PubMed

    Masuki, Shizue; Nose, Hiroshi

    2009-12-01

    We assessed whether increased cerebral activity suppressed baroreflex control of heart rate (HR) and, if so, whether this occurred prior to the onset of locomotion in daily activity of mice. We measured mean arterial pressure (MAP, arterial catheter), cerebral blood flow in the motor cortex (CBF, laser-Doppler flowmetry), and electroencephalogram in free-moving mice (n = 8) during 12 daytime hours. The contribution of baroreflex control of HR to MAP regulation was determined during a total resting period for approximately 8 h from the cross-correlation function (R(t)) between spontaneous changes in HR (HR) and MAP (MAP) every 4 s and the sensitivity was determined from HR/MAP where R(t) was significant (P < 0.05). The power density ratio of theta to delta wave band in electroencephalogram (theta/delta), determined every 4 s as an index of cerebral activity, was positively correlated with CBF during 73 +/- 3% of the total resting period (P < 0.05) and with R(t) during 59 +/- 2% (P < 0.05). When each measurement during the resting period was divided into seven bins according to the level of theta/delta, CBF was 91 +/- 2% in the lowest bin and 118 +/- 3% in the highest bin (P < 0.001), R(t) was 0.69 +/- 0.06 and 0.27 +/- 0.04 (P < 0.001) and HR/MAP (beats min(1) mmHg(1)) was 12.4 +/- 0.9 and 7.5 +/- 0.9 (P < 0.001), respectively, with significant correlations with theta/delta (all P < 0.002). Moreover, mice started to move in approximately 30 sec after the sequential increases of theta/delta and R(t), mice started to move at 5 times higher probability than after a given time, followed by a rapid increase in MAP by approximately 10 mmHg. These results suggest that increased cerebral activity suppresses baroreflex control of HR and this might be related to the start of voluntary locomotion with a rapid increase in MAP. PMID:19805749

  9. Increased cerebral activity suppresses baroreflex control of heart rate in freely moving mice.

    PubMed

    Masuki, Shizue; Nose, Hiroshi

    2009-12-01

    We assessed whether increased cerebral activity suppressed baroreflex control of heart rate (HR) and, if so, whether this occurred prior to the onset of locomotion in daily activity of mice. We measured mean arterial pressure (MAP, arterial catheter), cerebral blood flow in the motor cortex (CBF, laser-Doppler flowmetry), and electroencephalogram in free-moving mice (n = 8) during 12 daytime hours. The contribution of baroreflex control of HR to MAP regulation was determined during a total resting period for approximately 8 h from the cross-correlation function (R(t)) between spontaneous changes in HR (HR) and MAP (MAP) every 4 s and the sensitivity was determined from HR/MAP where R(t) was significant (P < 0.05). The power density ratio of theta to delta wave band in electroencephalogram (theta/delta), determined every 4 s as an index of cerebral activity, was positively correlated with CBF during 73 +/- 3% of the total resting period (P < 0.05) and with R(t) during 59 +/- 2% (P < 0.05). When each measurement during the resting period was divided into seven bins according to the level of theta/delta, CBF was 91 +/- 2% in the lowest bin and 118 +/- 3% in the highest bin (P < 0.001), R(t) was 0.69 +/- 0.06 and 0.27 +/- 0.04 (P < 0.001) and HR/MAP (beats min(1) mmHg(1)) was 12.4 +/- 0.9 and 7.5 +/- 0.9 (P < 0.001), respectively, with significant correlations with theta/delta (all P < 0.002). Moreover, mice started to move in approximately 30 sec after the sequential increases of theta/delta and R(t), mice started to move at 5 times higher probability than after a given time, followed by a rapid increase in MAP by approximately 10 mmHg. These results suggest that increased cerebral activity suppresses baroreflex control of HR and this might be related to the start of voluntary locomotion with a rapid increase in MAP.

  10. 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

  11. 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

  12. Acclimation of microalgae to wastewater environments involves increased oxidative stress tolerance activity.

    PubMed

    Osundeko, Olumayowa; Dean, Andrew P; Davies, Helena; Pittman, Jon K

    2014-10-01

    A wastewater environment can be particularly toxic to eukaryotic microalgae. Microalgae can adapt to these conditions but the specific mechanisms that allow strains to tolerate wastewater environments are unclear. Furthermore, it is unknown whether the ability to acclimate microalgae to tolerate wastewater is an innate or species-specific characteristic. Six different species of microalgae (Chlamydomonas debaryana, Chlorella luteoviridis, Chlorella vulgaris, Desmodesmus intermedius, Hindakia tetrachotoma and Parachlorella kessleri) that had never previously been exposed to wastewater conditions were acclimated over an 8-week period in secondary-treated municipal wastewater. With the exception of C. debaryana, acclimation to wastewater resulted in significantly higher growth rate and biomass productivity. With the exception of C. vulgaris, total chlorophyll content was significantly increased in all acclimated strains, while all acclimated strains showed significantly increased photosynthetic activity. The ability of strains to acclimate was species-specific, with two species, C. luteoviridis and P. kessleri, able to acclimate more efficiently to the stress than C. debaryana and D. intermedius. Metabolic fingerprinting of the acclimated and non-acclimated microalgae using Fourier transform infrared spectroscopy was able to differentiate strains on the basis of metabolic responses to the stress. In particular, strains exhibiting greater stress response and altered accumulation of lipids and carbohydrates could be distinguished. The acclimation to wastewater tolerance was correlated with higher accumulation of carotenoid pigments and increased ascorbate peroxidase activity.

  13. Formative evaluation of a motivational intervention for increasing physical activity in underserved youth.

    PubMed

    Wilson, Dawn K; Griffin, Sarah; Saunders, Ruth P; Evans, Alexandra; Mixon, Gary; Wright, Marcie; Beasley, Amelia; Umstattd, M Renee; Lattimore, Diana; Watts, Ashley; Freelove, Julie

    2006-08-01

    The present study was designed to develop an innovative motivational intervention (based on Self-Determination Theory and Social Cognitive Theory) to increase physical activity (PA) in underserved adolescents. Sixty-four adolescents (35 females, 29 males; 50% minority; 65% on reduced lunch program; ages 11-13 yr) participated in either an 8-week motivational intervention after-school (n = 32) or a typical after-school program (n = 32). The conceptual framework for the intervention targeted the social environment (perceived autonomy, perceived social support, participation, fun), cognitive mediators (perceived choice, self-efficacy, and relatedness/belongingness), and motivational orientation (intrinsic motivation, commitment, positive self-concept). Formative evaluation data was collected by staff through daily forms throughout the 8-week program and through observational data completed by independent objective observers during 2 weeks of the program. The major themes that were identified addressed theoretical concepts regarding the intervention and logistical issues in delivering the intervention. The data revealed information regarding the importance of the cognitive appropriateness of the PA and motivational activities, the environmental climate for promoting nurturing relationships, developing specific strategies for increasing intrinsic rather than extrinsic reinforcement, and developing methods for preventing social "cliques" and gender conflicts to maintain an appropriate level of support in the social climate. Themes for training staff included focusing on team building, leadership, and nurturing. This formative evaluation is being used to formalize a randomized trial to test the effects of a student-centered motivational intervention on increasing PA in underserved 6th graders.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity.

    PubMed

    Zhang, Yan; Kim, Ji-Yeon; Horst, Orapin; Nakano, Yukiko; Zhu, Li; Radlanski, Ralf J; Ho, Sunita; Den Besten, Pamela K

    2014-01-01

    Dental fluorosis is characterized by subsurface hypomineralization and increased porosity of enamel, associated with a delay in the removal of enamel matrix proteins. To investigate the effects of fluoride on ameloblasts, A/J mice were given 50 ppm sodium fluoride in drinking water for four weeks, resulting serum fluoride levels of 4.5 µM, a four-fold increase over control mice with no fluoride added to drinking water. MicroCT analyses showed delayed and incomplete mineralization of fluorosed incisor enamel as compared to control enamel. A microarray analysis of secretory and maturation stage ameloblasts microdissected from control and fluorosed mouse incisors showed that genes clustered with Mmp20 appeared to be less downregulated in maturation stage ameloblasts of fluorosed incisors as compared to control maturation ameloblasts. One of these Mmp20 co-regulated genes was the global chromatin organizer, special AT-rich sequence-binding protein-1 (SATB1). Immunohistochemical analysis showed increased SATB1 protein present in fluorosed ameloblasts compared to controls. In vitro, exposure of human ameloblast-lineage cells to micromolar levels of both NaF and AlF3 led to a significantly increase in SATB1 protein content, but not levels of Satb1 mRNA, suggesting a fluoride-induced mechanism protecting SABT1 from degradation. Consistent with this possibility, we used immunohistochemistry and Western blot to show that fluoride exposed ameloblasts had increased phosphorylated PKCα both in vivo and in vitro. This kinase is known to phosphorylate SATB1, and phosphorylation is known to protect SATB1 from degradation by caspase-6. In addition, production of cellular diacylglycerol (DAG) was significantly increased in fluorosed ameloblasts, suggesting that the increased phosphorylation of SATB1 may be related to an effect of fluoride to enhance Gαq activity of secretory ameloblasts.

  20. Fluorosed Mouse Ameloblasts Have Increased SATB1 Retention and Gαq Activity

    PubMed Central

    Zhang, Yan; Kim, Ji-Yeon; Horst, Orapin; Nakano, Yukiko; Zhu, Li; Radlanski, Ralf J.; Ho, Sunita; Besten, Pamela K. Den

    2014-01-01

    Dental fluorosis is characterized by subsurface hypomineralization and increased porosity of enamel, associated with a delay in the removal of enamel matrix proteins. To investigate the effects of fluoride on ameloblasts, A/J mice were given 50 ppm sodium fluoride in drinking water for four weeks, resulting serum fluoride levels of 4.5 µM, a four-fold increase over control mice with no fluoride added to drinking water. MicroCT analyses showed delayed and incomplete mineralization of fluorosed incisor enamel as compared to control enamel. A microarray analysis of secretory and maturation stage ameloblasts microdissected from control and fluorosed mouse incisors showed that genes clustered with Mmp20 appeared to be less downregulated in maturation stage ameloblasts of fluorosed incisors as compared to control maturation ameloblasts. One of these Mmp20 co-regulated genes was the global chromatin organizer, special AT-rich sequence-binding protein-1 (SATB1). Immunohistochemical analysis showed increased SATB1 protein present in fluorosed ameloblasts compared to controls. In vitro, exposure of human ameloblast-lineage cells to micromolar levels of both NaF and AlF3 led to a significantly increase in SATB1 protein content, but not levels of Satb1 mRNA, suggesting a fluoride-induced mechanism protecting SABT1 from degradation. Consistent with this possibility, we used immunohistochemistry and Western blot to show that fluoride exposed ameloblasts had increased phosphorylated PKCα both in vivo and in vitro. This kinase is known to phosphorylate SATB1, and phosphorylation is known to protect SATB1 from degradation by caspase-6. In addition, production of cellular diacylglycerol (DAG) was significantly increased in fluorosed ameloblasts, suggesting that the increased phosphorylation of SATB1 may be related to an effect of fluoride to enhance Gαq activity of secretory ameloblasts. PMID:25090413

  1. Increased activity of chondroitin sulfate-synthesizing enzymes during proliferation of arterial smooth muscle cells

    SciTech Connect

    Hollmann, J.; Thiel, J.; Schmidt, A.; Buddecke, E.

    1986-12-01

    Cultured arterial smooth muscle cells incorporate (/sup 35/S)sulfate into the extracellular chondroitin sulfate/dermatan sulfate containing proteoglycans at a higher rate in the phase of logarithmic growth than do non-dividing cells. The cell growth-dependent decrease in /sup 35/S incorporation with increasing cell density is accompanied by a decrease in the activity of chondroitin sulfate-synthesizing enzymes. The specific activity of xylosyl transferase, N-acetylgalactosaminyl transferase I and chondroitin sulfotransferase declines as the cells proceed from low to high densities. The corresponding correlation coefficients are 0.86, 0.91 and 0.89. The ratio of C-60H/C-40H sulfation of chondroitin shows a cell proliferation-dependent decrease indicating an inverse correlation of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase activity. The observed changes in the expression of enzyme activities are thought to have some implications in the pathogenesis of arteriosclerosis, the initial stages of which are characterized by proliferation of arterial smooth muscle cells.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Rapamycin protects against Aβ-induced synaptotoxicity by increasing presynaptic activity in hippocampal neurons.

    PubMed

    Ramírez, A E; Pacheco, C R; Aguayo, L G; Opazo, C M

    2014-09-01

    The mammalian target of rapamycin (mTOR) is involved in the regulation of learning and memory. Recently, rapamycin has been shown to be neuroprotective in models for Alzheimer's disease in an autophagy-dependent manner. Here we show that rapamycin exerts neuroprotection via a novel mechanism that involves presynaptic activation. Rapamycin increases the frequency of miniature excitatory postsynaptic currents and calcium transients of rat hippocampal primary neurons by a mechanism that involves the up regulation of SV2, a presynaptic vesicular protein linked to neurotransmitter release. Under these conditions, rapamycin-treated hippocampal neurons are resistant to the synaptotoxic effect induced by Aβ oligomers, suggesting that enhancers of presynaptic activity can be therapeutic agents for Alzheimer's disease. PMID:24794719

  8. Terminal complement activation is increased and associated with disease severity in CIDP.

    PubMed

    Quast, Isaak; Keller, Christian W; Hiepe, Falk; Tackenberg, Björn; Lünemann, Jan D

    2016-09-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. While both cell-mediated and humoral mechanisms contribute to its pathogenesis, the rapid clinical response to plasmapheresis implicates a circulating factor responsible for peripheral nerve injury. We report that treatment-naïve patients with CIDP show increased serum and CSF levels of the anaphylatoxin C5a and the soluble terminal complement complex (sTCC). Systemic terminal complement activation correlates with clinical disease severity as determined by the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. These data indicate that complement activation contributes to peripheral nerve injury and suggest that complement inhibition should be explored for its potential therapeutic merit in CIDP. PMID:27648461

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Yin Yang-1 increases apoptosis through Bax activation in pancreatic cancer cells

    PubMed Central

    Yang, Chuang; Liu, Xian; Peng, Yun-Peng; Jiang, Kui-Rong; Miao, Yi; Xu, Ze-Kuan

    2016-01-01

    The transcriptional regulator Yin Yang-1 (YY1) is a tumor suppressor known to be overexpressed in pancreatic cancer. We found that overexpression of YY1 promoted apoptosis and increased the expression and mitochondrial localization of the pro-apoptotic Bax protein in pancreatic cancer cell lines. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the BAX promoter. Moreover, YY1 promoted pancreatic cancer cell apoptosis through Bax transcriptional activation and subsequent translocation of Bax to the mitochondrial membrane, leading to cytochrome c release, and caspase activation.YY1 and BAX are co-expressed in pancreatic cancer tissues and higher BAX expression predicts better outcomes for patients. The ability of YY1 to promote apoptosis in pancreatic cancer cells suggests it may represent a valuable diagnostic and therapeutic target. PMID:27074573

  14. 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

  15. Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice

    PubMed Central

    Blednov, Y.A.; Benavidez, J.M.; Geil, C.; Perra, S.; Morikawa, H.; Harris, R.A.

    2011-01-01

    Previous studies showed that mice with genetic predisposition for high alcohol consumption as well as human alcoholics show changes in brain expression of genes related to immune signaling. In addition, mutant mice lacking genes related to immune function show decreased alcohol consumption (Blednov et al., in press), suggesting that immune signaling promotes alcohol consumption. To test the possibility that activation of immune signaling will increase alcohol consumption, we treated mice with lipopolysaccaride (LPS; 1 mg/kg, i.p.) and tested alcohol consumption in the continuous two-bottle choice test. To take advantage of the long-lasting activation of brain immune signaling by LPS, we measured drinking beginning one week or one month after LPS treatment and continued the studies for several months. LPS produced persistent increases in alcohol consumption in C57/Bl6 J (B6) inbred mice, FVBxB6F1 and B6xNZBF1 hybrid mice, but not in FVB inbred mice. To determine if this effect of LPS is mediated through binding to TLR4, we tested mice lacking CD14, a key component of TLR4 signaling. These null mutants showed no increase of alcohol intake after treatment with LPS. LPS treatment decreased ethanol-conditioned taste aversion but did not alter ethanol-conditioned place preference (B6xNZBF1 mice). Electro-physiological studies of dopamine neurons in the ventral tegmental area showed that pretreatment of mice with LPS decreased the neuronal firing rate. These results suggest that activation of immune signaling promotes alcohol consumption and alters certain aspects of alcohol reward/aversion. PMID:21266194

  16. 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.

  17. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    PubMed

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. PMID:25720500

  18. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans

    PubMed Central

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-01-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MSE, we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. PMID:25720500

  19. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    PubMed

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.

  20. 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

  1. Increased Plasma Dipeptidyl Peptidase-4 Activities in Patients with Coronary Artery Disease

    PubMed Central

    Yang, Guang; Li, Yuzi; Cui, Lan; Jiang, Haiying; Li, Xiang; Jin, Chunzi; Jin, Dehao; Zhao, Guangxian; Jin, Jiyong; Sun, Rui; Piao, Limei; Xu, Wenhu; Fang, Chenghu; Lei, Yanna; Yuan, Kuichang; Xuan, Chunhua; Ding, Dazi

    2016-01-01

    Dipeptidyl peptidase-4 (DPP4) is one of the most potent mammalian serine proteases participated in the pathogenesis of subclinical atherosclerosis. Here we investigated whether the plasma soluble form of DPP4 is associated with the prevalence of coronary artery disease (CAD) with and without diabetes mellitus (DM). A cross-sectional study was conducted of 496 aged 26–81 years with (n = 362) and without (n = 134) CAD. Plasma DPP4 activity, high sensitive C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein levels were measured. The coronary atherosclerotic plaques were evaluated by coronary angiography. The CAD patients with (n = 84) and without (n = 278) DM had significantly higher DPP4 levels (11.8 ± 3.1 vs. 6.9 ± 3.5 ng/mL, P<0.01) than the nonCAD subjects. The acute coronary syndrome patients (n = 299) had elevated DPP4 levels than those with stable angina patients (n = 83). CAD patients even without DM had increased plasma DPP4 activities as compared with nonCAD subjects (10.9 ± 4.9 vs. 6.4 ± 3.1, ng/L, P< 0.01). A linear regression analysis revealed that overall, the DPP4 levels were positively associated with LCL-C and hs-CRP levels as well as syntax scores. A multiple logistic regression analysis demonstrated that plasma DPP4 activity was independent predictor of CAD (odds ratio, 1.56; 95% CI, 1.19–1.73; P<0.01). Our study shows that increased DPP4 activity levels are associated with the presence of CAD and that the plasma DPP4 level serves as a novel biomarker for CAD even without DM. PMID:27654253

  2. Increase of mesenchymal stem cell migration by cannabidiol via activation of p42/44 MAPK.

    PubMed

    Schmuhl, Ellen; Ramer, Robert; Salamon, Achim; Peters, Kirsten; Hinz, Burkhard

    2014-02-01

    Migration and differentiation of mesenchymal stem cells (MSCs) are known to be involved in various regenerative processes such as bone healing. However, little is known about the pharmacotherapeutical options aiming at the mobilization and differentiation of MSCs. The present study therefore focussed on cannabinoids which have been demonstrated to exhibit tissue healing properties. Using Boyden chamber assays, the non-psychoactive phytocannabinoid cannabidiol (CBD) was found to increase the migration of adipose-derived MSCs in a time- and concentration-dependent manner. CBD-induced migration was inhibited by AM-630 (CB₂ receptor antagonist) and O-1602 (G protein-coupled receptor 55 [GRP55] agonist). Moreover, the promigratory effect of CBD was antagonized by inhibition of the p42/44 mitogen-activated protein kinase (MAPK) pathway which became activated upon CBD treatment. In line with this data, AM-630 and O-1602 attenuated CBD-induced p42/44 MAPK phosphorylation. A p42/44 MAPK-dependent promigratory effect was likewise demonstrated for the GPR55 antagonist O-1918 and the selective CB₂ receptor agonist JWH-133. Additional evidence for a functional effect of CBD on MSCs was provided by experiments demonstrating long-term stimulation with CBD to induce differentiation of MSCs into the osteoblastic lineage as evidenced by increased mineralization assessed by cresolphthalein complexone assay and enhanced activity of alkaline phosphatase. Collectively, this study demonstrates CBD to promote the migration of MSCs via activation of the CB₂ receptor and inhibition of GPR55 and to induce osteoblastic differentiation. CBD may therefore recruit MSCs to sites of calcifying tissue regeneration and subsequently support bone regeneration via an osteoanabolic action on MSCs.

  3. Tonic activity of carotid body chemoreceptors contributes to the increased sympathetic drive in essential hypertension.

    PubMed

    Siński, Maciej; Lewandowski, Jacek; Przybylski, Jacek; Bidiuk, Joanna; Abramczyk, Piotr; Ciarka, Agnieszka; Gaciong, Zbigniew

    2012-05-01

    Carotid chemoreceptors provoke an increase in muscle sympathetic nerve activation (MSNA) in response to hypoxia; they are also tonically active during normoxic breathing. The contribution of peripheral chemoreceptors to sympathetic activation in hypertension is incompletely understood. The aim of our study was to investigate the effect of chemoreceptor deactivation on sympathetic activity in untreated patients with hypertension. A total of 12 untreated hypertensive males and 11 male controls participated in this randomized, crossover, placebo-controlled study. MSNA, systolic blood pressure(BP), diastolic BP, heart rate (HR), electrocardiogram, hemoglobin oxygen saturation (Sat%) and respiratory movements were measured during repeated 10-min periods of respiration with 100% oxygen or 21% oxygen in a blinded fashion. Compared with controls, hypertensives had higher resting MSNA (38 ± 10 vs. 29 ± 0.9 burst per min, P<0.05), systolic BP (150 ± 12 vs. 124 ± 10 mm Hg, P< 0.001) and diastolic BP (92 ± 10 vs. 77 ± 9 mm Hg, P<0.005). Breathing 100% oxygen caused significant decrease in MSNA in hypertensive patients (38 ± 10 vs. 26 ± 8 burst per min and 100 ± 0 vs. 90 ± 10 arbitrary units, P<0.05) and no change in controls (29 ± 9 vs. 27 ± 7 burst per min and 100 ± 0 vs. 96 ± 11 arbitrary units). BP, respiratory frequency and end tidal CO(2) did not change during chemoreceptor deactivation with hyperoxia. HR decreased and Sat% increased in both the study groups. These results confirm the role of tonic chemoreceptor drive in the development of sympathetic overactivity in hypertension.

  4. Impaired long-term habituation is dissociated from increased locomotor activity after sensorimotor cortex compression.

    PubMed

    Moreira, Tiago; Cebers, Gvido; Salehi, Mehdi; Wägner, Anna; Liljequist, Sture

    2006-02-15

    Behavioural habituation to a novel environment is a simple form of learning in rodents. We studied the habituation and locomotor activity (LMA) of Wistar rats subjected to unilateral, transient (30min) extradural compression (EC) of the right sensorimotor cortex. One group of rats was tested every 24h during the first 5 days (D1-D5) post-EC. Two other groups were tested for the first time in the LMA boxes on D3 and D6 post-EC and their performance was compared with the group tested on D1 (activity in a novel environment). Total and center locomotion, vertical activity and time spent in the center of the LMA box were reduced on D1 post-EC and normalized by D2. The EC-induced motor paresis was undetectable on the rotarod by D2 and on the beam-walking by D3. Total locomotion, vertical activity and time spent in the center of EC-rats significantly increased from D1 to D3. EC caused neurodegeneration in the cortex, caudate putamen and thalamus as detected by Fluoro-Jade staining. The size of the cortical damage decreased from D2 to D5 in the medial and caudal regions of the compressed hemisphere, in accordance with recovery of motor function. LMA provided additional information in the follow-up of recovery from brain injury and habituation to the environment. Thus, long-term, inter-session habituation was impaired from D1 to D3 but dissociated from increased LMA intra-session on D3, when the motor deficits pro