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Sample records for potentiates locomotor sensitization

  1. Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

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    Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2014-02-01

    It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Limitations to the Generality of Cocaine Locomotor Sensitization

    OpenAIRE

    Marusich, Julie A.; Branch, Marc N.; Dallery, Jesse

    2008-01-01

    Repeated exposure to cocaine often leads to tolerance to effects on operant behavior, whereas sensitization often develops to effects on locomotor activity. The purpose of the present set of experiments was to examine if locomotor sensitization to cocaine would develop in the presence or absence of an operant contingency in rats. In Experiment 1, rats lever pressed on an FR schedule of reinforcement, and were administered chronic cocaine. Tolerance to effects of cocaine on lever pressing deve...

  3. Locomotor sensitization to ethanol: Contribution of b-Endorphin

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    Stephani eDempsey

    2012-08-01

    Full Text Available Alcohol use disorders, like all drug addictions, involve a constellation of adaptive changes throughout the brain. Neural activity underlying changes in the rewarding properties of alcohol reflect changes in dopamine transmission in mesolimbic and nigrostriatal pathways and these effects are modulated by endogenous opioids such as b-Endorphin. In order to study the role of b-Endorphin in the development of locomotor sensitization to repeated EtOH exposure, we tested transgenic mice that vary in their capacity to synthesize this peptide as a result of constitutive modification of the Pomc gene. Our results indicate that mice deficient in b-Endorphin show attenuated locomotor activation following an acute injection of EtOH (2 g/kg and, in contrast to wildtype mice, fail to demonstrate locomotor sensitization after 12 days of repeated EtOH injections. These data support the idea that b-Endorphin modulates the locomotor effects of EtOH and contributes to the neuroadaptive changes associated with chronic use.

  4. Differential housing and novelty response: Protection and risk from locomotor sensitization.

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    Garcia, Erik J; Haddon, Tara N; Saucier, Donald A; Cain, Mary E

    2017-03-01

    High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce

  5. High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster.

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    Filošević, Ana; Al-Samarai, Sabina; Andretić Waldowski, Rozi

    2018-01-01

    Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila . We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per) , Clock (Clk) , and cycle (cyc) . The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization

  6. High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster

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    Ana Filošević

    2018-02-01

    Full Text Available Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila. We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per, Clock (Clk, and cycle (cyc. The locomotor sensitization that is present in timeless (tim and pigment dispersing factor (pdf mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor

  7. Cocaine locomotor activation, sensitization and place preference in six inbred strains of mice

    Science.gov (United States)

    2011-01-01

    Background The expanding set of genomics tools available for inbred mouse strains has renewed interest in phenotyping larger sets of strains. The present study aims to explore phenotypic variability among six commonly-used inbred mouse strains to both the rewarding and locomotor stimulating effects of cocaine in a place conditioning task, including several strains or substrains that have not yet been characterized for some or all of these behaviors. Methods C57BL/6J (B6), BALB/cJ (BALB), C3H/HeJ (C3H), DBA/2J (D2), FVB/NJ (FVB) and 129S1/SvImJ (129) mice were tested for conditioned place preference to 20 mg/kg cocaine. Results Place preference was observed in most strains with the exception of D2 and 129. All strains showed a marked increase in locomotor activity in response to cocaine. In BALB mice, however, locomotor activation was context-dependent. Locomotor sensitization to repeated exposure to cocaine was most significant in 129 and D2 mice but was absent in FVB mice. Conclusions Genetic correlations suggest that no significant correlation between conditioned place preference, acute locomotor activation, and locomotor sensitization exists among these strains indicating that separate mechanisms underlie the psychomotor and rewarding effects of cocaine. PMID:21806802

  8. Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains.

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    Wiltshire, T; Ervin, R B; Duan, H; Bogue, M A; Zamboni, W C; Cook, S; Chung, W; Zou, F; Tarantino, L M

    2015-03-01

    Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  9. Dentate gyrus neurogenesis ablation via cranial irradiation enhances morphine self-administration and locomotor sensitization.

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    Bulin, Sarah E; Mendoza, Matthew L; Richardson, Devon R; Song, Kwang H; Solberg, Timothy D; Yun, Sanghee; Eisch, Amelia J

    2018-03-01

    Adult dentate gyrus (DG) neurogenesis is important for hippocampal-dependent learning and memory, but the role of new neurons in addiction-relevant learning and memory is unclear. To test the hypothesis that neurogenesis is involved in the vulnerability to morphine addiction, we ablated adult DG neurogenesis and examined morphine self-administration (MSA) and locomotor sensitization. Male Sprague-Dawley rats underwent hippocampal-focused, image-guided X-ray irradiation (IRR) to eliminate new DG neurons or sham treatment (Sham). Six weeks later, rats underwent either MSA (Sham = 16, IRR = 15) or locomotor sensitization (Sham = 12, IRR = 12). Over 21 days of MSA, IRR rats self-administered ~70 percent more morphine than Sham rats. After 28 days of withdrawal, IRR rats pressed the active lever 40 percent more than Sham during extinction. This was not a general enhancement of learning or locomotion, as IRR and Sham groups had similar operant learning and inactive lever presses. For locomotor sensitization, both IRR and Sham rats sensitized, but IRR rats sensitized faster and to a greater extent. Furthermore, dose-response revealed that IRR rats were more sensitive at a lower dose. Importantly, these increases in locomotor activity were not apparent after acute morphine administration and were not a byproduct of irradiation or post-irradiation recovery time. Therefore, these data, along with other previously published data, indicate that reduced hippocampal neurogenesis confers vulnerability for multiple classes of drugs. Thus, therapeutics to specifically increase or stabilize hippocampal neurogenesis could aid in preventing initial addiction as well as future relapse. © 2017 Society for the Study of Addiction.

  10. Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice

    DEFF Research Database (Denmark)

    Schmidt, Lene S; Miller, Anthony D; Lester, Deranda B

    2010-01-01

    showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release......-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M(5) receptor. These results support the concept that the M(5) receptor modulates effects of addictive drugs....

  11. The Rewarding and Locomotor-Sensitizing Effects of Repeated Cocaine Administration are Distinct and Separable in Mice

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    Riday, Thorfinn T.; Kosofsky, Barry E.; Malanga, C.J.

    2011-01-01

    Repeated psychostimulant exposure progressively increases their potency to stimulate motor activity in rodents. This behavioral or locomotor sensitization is considered a model for some aspects of drug addiction in humans, particularly drug craving during abstinence. However, the role of increased motor behavior in drug reward remains incompletely understood. Intracranial self-stimulation (ICSS) was measured concurrently with locomotor activity to determine if acute intermittent cocaine administration had distinguishable effects on motor behavior and perception of brain stimulation-reward (BSR) in the same mice. Sensitization is associated with changes in neuronal activity and glutamatergic neurotransmission in brain reward circuitry. Expression of AMPA receptor subunits (GluR1 and GluR2) and CRE binding protein (CREB) was measured in the ventral tegmental area (VTA), dorsolateral striatum (STR) and nucleus accumbens (NAc) before and after a sensitizing regimen of cocaine, with and without ICSS. Repeated cocaine administration sensitized mice to its locomotor stimulating effects but not its ability to potentiate BSR. ICSS increased GluR1 in the VTA but not NAc or STR, demonstrating selective changes in protein expression with electrical stimulation of discrete brain structures. Repeated cocaine reduced GluR1, GluR2 and CREB expression in the NAc, and reductions of GluR1 and GluR2 but not CREB were further enhanced by ICSS. These data suggest that the effects of repeated cocaine exposure on reward and motor processes are dissociable in mice, and that reduction of excitatory neurotransmission in the NAc may predict altered motor function independently from changes in reward perception. PMID:22197517

  12. A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

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    Zovkic, Iva B; McCormick, Cheryl M

    2017-11-14

    Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

  13. GABAB Receptor Stimulation Accentuates the Locomotor Effects of Morphine in Mice Bred for Extreme Sensitivity to the Stimulant Effects of Ethanol

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    Holstein, Sarah E.; Phillips, Tamara J.

    2006-01-01

    Mice selectively bred for divergent sensitivity to the locomotor stimulant effects of ethanol (FAST and SLOW) also differ in their locomotor response to morphine. The GABAB receptor has been implicated in the mediation of locomotor stimulation to both ethanol and morphine, and a reduction in ethanol-induced stimulation has been found with the GABAB receptor agonist baclofen in FAST mice. We hypothesized that GABAB receptor activation would also attenuate the locomotor stimulant responses to m...

  14. CRFR1 in the ventromedial caudate putamen modulates acute stress-enhanced expression of cocaine locomotor sensitization.

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    Liu, Shuli; Wang, Zhiyan; Li, Yijing; Sun, Xiaowei; Ge, Feifei; Yang, Mingda; Wang, Xinjuan; Wang, Na; Wang, Junkai; Cui, Cailian

    2017-07-15

    Repeated exposure to psychostimulants induces a long-lasting enhancement of locomotor activity called behavioral sensitization, which is often reinforced by stress after drug withdrawal. The mechanisms underlying these phenomena remain elusive. Here we explored the effects of acute stress 3 or 14 days after the cessation of chronic cocaine treatment on the expression of locomotor sensitization induced by a cocaine challenge in rats and the key brain region and molecular mechanism underlying the phenomenon. A single session of forced swimming, as an acute stress (administered 2 days after the cessation of cocaine), significantly enhanced the expression of cocaine locomotor sensitization 14 days after the final cocaine injection (challenge at 12 days after acute stress) but not 3 days after the cessation of cocaine (challenge at 1 day after acute stress). The result indicated that acute stress enhanced the expression of cocaine locomotor sensitization after incubation for 12 days rather than 1 day after the last cocaine injection. Moreover, the enhancement in locomotor sensitization was paralleled by a selective increase in the number of the c-Fos + cells, the level of CRFR1 mRNA in the ventromedial caudate putamen (vmCPu). Furthermore, the enhancement was significantly attenuated by CRFR1 antagonist NBI-27914 into the vmCPu, implying that the up-regulation of CRFR1 in the vmCPu seems to be critical in the acute stress-enhanced expression of cocaine locomotor sensitization. The findings demonstrate that the long-term effect of acute stress on the expression of cocaine locomotor sensitization is partially mediated by CRFR1 in the vmCPu. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Individual differences in ethanol locomotor sensitization are associated with dopamine D1 receptor intra-cellular signaling of DARPP-32 in the nucleus accumbens.

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    Karina Possa Abrahao

    Full Text Available In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as "sensitized" and the 33% with the lowest levels as "non-sensitized". The latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 µg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. The nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. The functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of

  16. Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine

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    Sukhanov, Ilya; Dorofeikova, Mariia; Dolgorukova, Antonina; Dorotenko, Artem; Gainetdinov, Raul R.

    2018-01-01

    Trace amine-associated receptor 1 (TAAR1) has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg). The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted. PMID:29681856

  17. Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine

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    Ilya Sukhanov

    2018-04-01

    Full Text Available Trace amine-associated receptor 1 (TAAR1 has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg. The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted.

  18. Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

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    Giardino, William J; Mark, Gregory P; Stenzel-Poore, Mary P; Ryabinin, Andrey E

    2012-02-01

    Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5-10 mg/kg). While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction.

  19. Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats.

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    Strong, C E; Schoepfer, K J; Dossat, A M; Saland, S K; Wright, K N; Kabbaj, M

    2017-07-15

    Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction. Copyright © 2017. Published by Elsevier Ltd.

  20. Reversal of apomorphine locomotor sensitization by a single post-conditioning trial treatment with a low autoreceptor dose of apomorphine: a memory re-consolidation approach.

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    Carrera, Marinete Pinheiro; Carey, Robert J; Dias, Flávia Regina Cruz; de Matos, Liana Wermelinger

    2011-07-01

    Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of apomorphine (2.0mg/kg). Two days following a 5 session sensitization induction phase, a brief 5min non-drug test for conditioning was conducted. Only the paired groups exhibited locomotor stimulant conditioned response effects. Immediately following this brief test for conditioning, the paired and the unpaired groups received injections of 0.05mg/kg apomorphine, 2.0mg/kg apomorphine or vehicle designed to differentially impact memory re-consolidation of the conditioning. Two days later, all groups received a sensitization challenge test with 2.0mg/kg apomorphine. The 2.0mg/kg apomorphine post-trial treatment potentiated sensitization while the 0.05mg/kg eliminated sensitization. These effects were only observed in the paired groups. The activation of dopaminergic systems by the high dose of apomorphine strengthened the drug/environment association whereas the inhibition of dopamine activity by the low auto-receptor dose eliminated this association. The results point to the importance of conditioning to context specific sensitization and targeting memory re-consolidation of conditioning as a paradigm to modify sensitization. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice.

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    Emil Egecioglu

    Full Text Available The gastrointestinal peptide glucagon-like peptide 1 (GLP-1 is known to regulate consummatory behavior and is released in response to nutrient ingestion. Analogues of this peptide recently emerged as novel pharmacotherapies for treatment of type II diabetes since they reduce gastric emptying, glucagon secretion as well as enhance glucose-dependent insulin secretion. The findings that GLP-1 targets reward related areas including mesolimbic dopamine areas indicate that the physiological role of GLP-1 extends beyond food intake and glucose homeostasis control to include reward regulation. The present series of experiments was therefore designed to investigate the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4, on established nicotine-induced effects on the mesolimbic dopamine system in mice. Specifically, we show that treatment with Ex4, at a dose with no effect per se, attenuate nicotine-induced locomotor stimulation, accumbal dopamine release as well as the expression of conditioned place preference in mice. In accordance, Ex4 also blocks nicotine-induced expression of locomotor sensitization in mice. Given that development of nicotine addiction largely depends on the effects of nicotine on the mesolimbic dopamine system these findings indicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for nicotine cessations in humans.

  2. Local field potentials in the ventral tegmental area during cocaine-induced locomotor activation: Measurements in freely moving rats.

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    Harris Bozer, Amber L; Li, Ai-Ling; Sibi, Jiny E; Bobzean, Samara A M; Peng, Yuan B; Perrotti, Linda I

    2016-03-01

    The ventral tegmental area (VTA) has been established as a critical nucleus for processing behavioral changes that occur during psychostimulant use. Although it is known that cocaine induced locomotor activity is initiated in the VTA, not much is known about the electrical activity in real time. The use of our custom-designed wireless module for recording local field potential (LFP) activity provides an opportunity to confirm and identify changes in neuronal activity within the VTA of freely moving rats. The purpose of this study was to investigate the changes in VTA LFP activity in real time that underlie cocaine induced changes in locomotor behavior. Recording electrodes were implanted in the VTA of rats. Locomotor behavior and LFP activity were simultaneously recorded at baseline, and after saline and cocaine injections. Results indicate that cocaine treatment caused increases in both locomotor behavior and LFP activity in the VTA. Specifically, LFP activity was highest during the first 30 min following the cocaine injection and was most robust in Delta and Theta frequency bands; indicating the role of low frequency VTA activity in the initiation of acute stimulant-induced locomotor behavior. Our results suggest that LFP recording in freely moving animals can be used in the future to provide valuable information pertaining to drug induced changes in neural activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

    Science.gov (United States)

    Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

    2015-01-01

    Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

  4. Potential contributions of training intensity on locomotor performance in individuals with chronic stroke.

    Science.gov (United States)

    Holleran, Carey L; Rodriguez, Kelly S; Echauz, Anthony; Leech, Kristan A; Hornby, T George

    2015-04-01

    Many interventions can improve walking ability of individuals with stroke, although the training parameters that maximize recovery are not clear. For example, the contribution of training intensity has not been well established and may contribute to the efficacy of many locomotor interventions. The purpose of this preliminary study was to evaluate the effects of locomotor training intensity on walking outcomes in individuals with gait deficits poststroke. Using a randomized cross-over design, 12 participants with chronic stroke (>6-month duration) performed either high-intensity (70%-80% of heart rate reserve; n = 6) or low-intensity (30%-40% heart rate reserve; n = 6) locomotor training for 12 or fewer sessions over 4 to 5 weeks. Four weeks following completion, the alternate training intervention was performed. Training intensity was manipulated by adding loads or applying resistance during walking, with similar speeds, durations, and amount of stepping practice between conditions. Greater increases in 6-Minute Walk Test performance were observed following high-intensity training compared with low-intensity training. A significant interaction of intensity and order was also observed for 6-Minute Walk Test and peak treadmill speed, with the largest changes in those who performed high-intensity training first. Moderate correlations were observed between locomotor outcomes and measures of training intensity. This study provides the first evidence that the intensity of locomotor practice may be an important independent determinant of walking outcomes poststroke. In the clinical setting, the intensity of locomotor training can be manipulated in many ways, although this represents only 1 parameter to consider.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A90).

  5. Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization.

    Science.gov (United States)

    Cohen, Ami; Whitfield, Timothy W; Kreifeldt, Max; Koebel, Pascale; Kieffer, Brigitte L; Contet, Candice; George, Olivier; Koob, George F

    2014-01-01

    Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn), are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc) mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV) vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn) or a scrambled shRNA (AAV-shScr) as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST). Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p.), followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition.

  6. Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization.

    Directory of Open Access Journals (Sweden)

    Ami Cohen

    Full Text Available Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn, are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn or a scrambled shRNA (AAV-shScr as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST. Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p., followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition.

  7. Comparative potentialities of X-ray and remote thermographic diagnosis of locomotor system diseases and injuries

    International Nuclear Information System (INIS)

    Rozenfel'd, L.G.; Ternovoj, N.K.; Samokhin, A.V.; Likhosherst, E.K.

    1988-01-01

    The advisability of applying remote infrared tomography to diagnoze locomotor system diseases and injuries is substantiated. 764 patients with different bone and tissue system diseases and injuries are examined. Thermosemiotics in the case of deforming arthrosis of knee and hip joints, inflammatory diseases of joints of various ethiologies, acute chronic osteomyelitis and its exacerbation, is described. The place of remote infrared thermography in the complecx diagnostic examination of a given contingent of patients, is determined. 6 refs.; 4 figs

  8. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

    Directory of Open Access Journals (Sweden)

    Paul Fredrickson

    2014-01-01

    Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

  9. Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

    Science.gov (United States)

    Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

    2015-01-01

    Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. Copyright © 2014. Published by Elsevier Inc.

  10. Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine-stimulated locomotor activity are sensitized by previous sexual experience in female Syrian hamsters.

    Science.gov (United States)

    Bradley, K C; Meisel, R L

    2001-03-15

    Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes neuronal responses in the nucleus accumbens to amphetamine. Using immunocytochemical labeling, c-Fos expression in different subregions (shell vs core at the rostral, middle, and caudal levels) of the nucleus accumbens was examined in female hamsters that had varying amounts of sexual experience. Female hamsters, given either 6 weeks of sexual experience or remaining sexually naive, were tested for sexual behavior by exposure to adult male hamsters. Previous sexual experience increased c-Fos labeling in the rostral and caudal levels but not in the middle levels of the nucleus accumbens. Testing for sexual behavior increased labeling in the core, but not the shell, of the nucleus accumbens. To validate that female sexual behavior can sensitize neurons in the mesolimbic dopamine pathway, the locomotor responses of sexually experienced and sexually naive females to an amphetamine injection were then compared. Amphetamine increased general locomotor activity in all females. However, sexually experienced animals responded sooner to amphetamine than did sexually naive animals. These data indicate that female sexual behavior can activate neurons in the nucleus accumbens and that sexual experience can cross-sensitize neuronal responses to amphetamine. In addition, these results provide additional evidence for functional differences between the shell and core of the nucleus accumbens and across its anteroposterior axis.

  11. Selectively bred crossed high-alcohol-preferring mice drink to intoxication and develop functional tolerance, but not locomotor sensitization during free-choice ethanol access.

    Science.gov (United States)

    Matson, Liana M; Kasten, Chelsea R; Boehm, Stephen L; Grahame, Nicholas J

    2014-01-01

    Crossed high-alcohol-preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines and demonstrate blood ethanol concentrations (BECs) during free-choice drinking reminiscent of those observed in alcohol-dependent humans. In this report, we investigated the relationship between free-choice drinking, intoxication, tolerance, and sensitization in cHAP mice. We hypothesized that initially mice would become ataxic after drinking alcohol, but that increased drinking over days would be accompanied by increasing tolerance to the ataxic effects of ethanol (EtOH). Male and female cHAP mice had free-choice access to 10% EtOH and water (E), while Water mice (W) had access to water alone. In experiment 1, the first drinking experience was monitored during the dark portion of the cycle. Once E mice reached an average intake rate of ≥1.5 g/kg/h, they, along with W mice, were tested for footslips on a balance beam, and BECs were assessed. In experiments 2, 3, and 4, after varying durations of free-choice 10% EtOH access (0, 3, 14, or 21 days), mice were challenged with 20% EtOH and tested for number of footslips on a balance beam or locomotor stimulant response. Blood was sampled for BEC determination. We found that cHAP mice rapidly acquire alcohol intakes that lead to ataxia. Over time, cHAP mice developed behavioral tolerance to the ataxic effects of alcohol, paralleled by escalating alcohol consumption. However, locomotor sensitization did not develop following 14 days of free-choice EtOH access. Overall, we observed increases in free-choice drinking with extended alcohol access paralleled by increases in functional tolerance, but not locomotor sensitization. These data support our hypothesis that escalating free-choice drinking over days in cHAP mice is driven by tolerance to alcohol's behavioral effects. These data are the first to demonstrate that escalating free-choice consumption is accompanied by increasing alcohol tolerance. In

  12. Antimicrobial activities, toxinogenic potential and sensitivity to ...

    African Journals Online (AJOL)

    Antimicrobial activities, toxinogenic potential and sensitivity to antibiotics of ... Bacillus species showed variable ability to inhibit bacterial and/or fungal species. ... to produce Mbuja in order to better control the fermentation process of Mbuja ...

  13. Stress-induced locomotor sensitization to amphetamine in adult, but not in adolescent rats, is associated with increased expression of ΔFosB in the nucleus accumbens.

    Directory of Open Access Journals (Sweden)

    Paulo Eduardo Carneiro de Oliveira

    2016-09-01

    Full Text Available While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively were restrained for 2 hours once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p. and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.

  14. SLO-1-channels of parasitic nematodes reconstitute locomotor behaviour and emodepside sensitivity in Caenorhabditis elegans slo-1 loss of function mutants.

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    Claudia Welz

    2011-04-01

    Full Text Available The calcium-gated potassium channel SLO-1 in Caenorhabditis elegans was recently identified as key component for action of emodepside, a new anthelmintic drug with broad spectrum activity. In this study we identified orthologues of slo-1 in Ancylostoma caninum, Cooperia oncophora, and Haemonchus contortus, all important parasitic nematodes in veterinary medicine. Furthermore, functional analyses of these slo-1 orthologues were performed using heterologous expression in C. elegans. We expressed A. caninum and C. oncophora slo-1 in the emodepside-resistant genetic background of the slo-1 loss-of-function mutant NM1968 slo-1(js379. Transformants expressing A. caninum slo-1 from C. elegans slo-1 promoter were highly susceptible (compared to the fully emodepside-resistant slo-1(js379 and showed no significant difference in their emodepside susceptibility compared to wild-type C. elegans (p = 0.831. Therefore, the SLO-1 channels of A. caninum and C. elegans appear to be completely functionally interchangeable in terms of emodepside sensitivity. Furthermore, we tested the ability of the 5' flanking regions of A. caninum and C. oncophora slo-1 to drive expression of SLO-1 in C. elegans and confirmed functionality of the putative promoters in this heterologous system. For all transgenic lines tested, expression of either native C. elegans slo-1 or the parasite-derived orthologue rescued emodepside sensitivity in slo-1(js379 and the locomotor phenotype of increased reversal frequency confirming the reconstitution of SLO-1 function in the locomotor circuits. A potent mammalian SLO-1 channel inhibitor, penitrem A, showed emodepside antagonising effects in A. caninum and C. elegans. The study combined the investigation of new anthelmintic targets from parasitic nematodes and experimental use of the respective target genes in C. elegans, therefore closing the gap between research approaches using model nematodes and those using target organisms

  15. Cocaine- and amphetamine-regulated transcript peptide in the nucleus accumbens shell inhibits cocaine-induced locomotor sensitization to transient over-expression of α-Ca2+ /calmodulin-dependent protein kinase II.

    Science.gov (United States)

    Xiong, Lixia; Meng, Qing; Sun, Xi; Lu, Xiangtong; Fu, Qiang; Peng, Qinghua; Yang, Jianhua; Oh, Ki-Wan; Hu, Zhenzhen

    2018-01-04

    Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine-induced locomotor activity is related to a reduction in cocaine-enhanced phosphorylated Ca 2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca 2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus-transfected CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca 2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-over-expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine-induced locomotor sensitization. © 2018 International Society for Neurochemistry.

  16. Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Swann Alan C

    2006-01-01

    Full Text Available Abstract Background Methylphenidate (MPD is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA, nucleus accumbens (NAc, and prefrontal cortex (PFC. Methods The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39 rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p. on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10. Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min. Results Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% ± 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% ± 5.9% after 2.5 mg/kg MPD, and 56.5% ± 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of

  17. ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine.

    Science.gov (United States)

    Berezniuk, Iryna; Rodriguiz, Ramona M; Zee, Michael L; Marcus, David J; Pintar, John; Morgan, Daniel J; Wetsel, William C; Fricker, Lloyd D

    2017-11-01

    To identify neuropeptides that are regulated by cocaine, we used a quantitative peptidomic technique to examine the relative levels of neuropeptides in several regions of mouse brain following daily intraperitoneal administration of 10 mg/kg cocaine or saline for 7 days. A total of 102 distinct peptides were identified in one or more of the following brain regions: nucleus accumbens, caudate putamen, frontal cortex, and ventral tegmental area. None of the peptides detected in the caudate putamen or frontal cortex were altered by cocaine administration. Three peptides in the nucleus accumbens and seven peptides in the ventral tegmental area were significantly decreased in cocaine-treated mice. Five of these ten peptides are derived from proSAAS, a secretory pathway protein and neuropeptide precursor. To investigate whether proSAAS peptides contribute to the physiological effects of psychostimulants, we examined acute responses to cocaine and amphetamine in the open field with wild-type (WT) and proSAAS knockout (KO) mice. Locomotion was stimulated more robustly in the WT compared to mutant mice for both psychostimulants. Behavioral sensitization to amphetamine was not maintained in proSAAS KO mice and these mutants failed to sensitize to cocaine. To determine whether the rewarding effects of cocaine were altered, mice were tested in conditioned place preference (CPP). Both WT and proSAAS KO mice showed dose-dependent CPP to cocaine that was not distinguished by genotype. Taken together, these results suggest that proSAAS-derived peptides contribute differentially to the behavioral sensitization to psychostimulants, while the rewarding effects of cocaine appear intact in mice lacking proSAAS. © 2017 International Society for Neurochemistry.

  18. Effects of BDNF receptor antagonist on the severity of physical and psychological dependence, morphine-induced locomotor sensitization and the ventral tegmental area-nucleus accumbens BDNF levels in morphine- dependent and withdrawn rats.

    Science.gov (United States)

    Khalil-Khalili, Masoumeh; Rashidy-Pour, Ali; Bandegi, Ahmad Reza; Yousefi, Behpoor; Jorjani, Hassan; Miladi-Gorji, Hossein

    2018-03-06

    This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and psychological dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert-Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Capacity of novelty-induced locomotor activity and the hole-board test to predict sensitivity to the conditioned rewarding effects of cocaine.

    Science.gov (United States)

    Arenas, M Carmen; Daza-Losada, Manuel; Vidal-Infer, Antonio; Aguilar, Maria A; Miñarro, José; Rodríguez-Arias, Marta

    2014-06-22

    Novelty-seeking in rodents, defined as enhanced specific exploration of novel situations, is considered to predict the response of animals to drugs of abuse and, thus, allow "drug-vulnerable" individuals to be identified. The main objective of this study was to assess the predictive ability of two well-known paradigms of the novelty-seeking trait - novelty-induced locomotor activity (which distinguishes High- and Low-Responder mice, depending on their motor activity) and the hole-board test (which determines High- and Low-Novelty Seeker mice depending on the number of head dips they perform) - to identify subjects that would subsequently be more sensitive to the conditioned rewarding effects of cocaine in a population of young adult (PND 56) and adolescent (PND 35) OF1 mice of both sexes. Conditioned place preference (CPP), a useful tool for evaluating the sensitivity of individuals to the incentive properties of addictive drugs, was induced with a sub-threshold dose of cocaine (1 mg/kg, i.p.). Our results showed that novelty-induced motor activity had a greater predictive capacity to identify "vulnerable-drug" individuals among young-adult mice (PND 56), while the hole-board test was more effective in adolescents (PND 35). High-NR young-adults, which presented higher motor activity in the first ten minutes of the test (novelty-reactivity), were 3.9 times more likely to develop cocaine-induced CPP than Low-NR young-adults. When total activity (1h) was evaluated (novelty-habituation), only High-R (novelty-non-habituating) young-adult male and Low-R (novelty-habituating) female mice produced a high conditioning score. However, only High-Novelty Seeker male and female adolescents and Low-Novelty Seeker female young-adult animals (according to the hole-board test), acquired cocaine-induced CPP. These findings should contribute to the development of screening methods for identifying at-risk human drug users and prevention strategies for those with specific

  20. Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

    Science.gov (United States)

    Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

    2011-12-01

    Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (pbrain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

    Directory of Open Access Journals (Sweden)

    Dimitri Ryczko

    2017-05-01

    Full Text Available In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.

  2. Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats.

    Science.gov (United States)

    Serafine, Katherine M; Labay, Caitlin; France, Charles P

    2016-08-01

    Eating a diet high in fat can lead to obesity, chronic metabolic disease, and increased inflammation in both the central and peripheral nervous systems. Dietary supplements that are high in omega-3 polyunsaturated fatty acids can reduce or prevent these negative health consequences in rats. Eating high fat chow also increases the sensitivity of rats to behavioral effects of drugs acting on dopamine systems (e.g., cocaine), and this effect is greatest in adolescent females. The present experiment tested the hypothesis that dietary supplementation with fish oil prevents high fat chow induced increases in sensitivity to cocaine in adolescent female rats. Female Sprague-Dawley rats (post-natal day 25-27) ate standard laboratory chow (5.7% fat), high fat chow (34.4% fat), or high fat chow supplemented with fish oil (20% w/w). Cocaine dose dependently (1-17.8mg/kg) increased locomotion and induced sensitization across 6 weeks of once-weekly testing in all rats; however, these effects were greatest in rats eating high fat chow. Dietary supplementation with fish oil prevented enhanced locomotion and sensitization in rats eating high fat chow. There were no differences in inflammatory markers in plasma or the hypothalamus among dietary conditions. These results demonstrate that dietary supplementation with fish oil can prevent high fat diet-induced sensitization to cocaine, but they fail to support the view that these effects are due to changes in proinflammatory cytokines. These data add to a growing literature on the relationship between diet and drug abuse and extend the potential health benefits of fish oil to stimulant drug abuse prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Statistical Analysis of Zebrafish Locomotor Response.

    Science.gov (United States)

    Liu, Yiwen; Carmer, Robert; Zhang, Gaonan; Venkatraman, Prahatha; Brown, Skye Ashton; Pang, Chi-Pui; Zhang, Mingzhi; Ma, Ping; Leung, Yuk Fai

    2015-01-01

    Zebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling's T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling's T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure.

  4. Relationship between intrinsic radiation sensitivity and metastatic potential

    International Nuclear Information System (INIS)

    Lewis, Anne M.; Mei, Su; Doty, Jay; Chen Yi; Pardo, Francisco S.

    1996-01-01

    Purpose: Prior studies emphasized genetic modulation of tumorigenicity, and experimental metastatic potential in cells transfected with oncogenes. Whether the intrinsic radiation sensitivity of cells might correlate with parallel changes in metastatic potential is unknown. Methods and Materials: Rat embryo cells (REC) were transfected with the following oncogenes, and where appropriate, with corresponding selection markers: pCMV neopEJ6.6ras, pEJ6.6ras/v-myc, pE1a, and pEJ6-.6ras/E1a. Individual transfectant clones and corresponding pooled cellular populations were propagated in selective medium. In vitro cellular radiation sensitivity was determined via clonogenic assays, a minimum of three, by standard techniques and individual SF 2 and MID parameters determined. Tumorigenicity was defined as the number of tumors forming following the injection of 1 x 10 5 - 1 x 10 6 cells into the axillary pouch of three different strains of immune-deficient mice. Animals were killed once resultant tumors reached a maximum size of 1.5-2.0 cm in maximum diameter. For determination of experimental metastatic potential, between 1 x 10 5 -1 x 10 6 cells were injected into the tail veins of litter-matched sibling mice in parallel to the tumorigenicity studies. Results: Radiobiologic studies indicate similar levels of radiation sensitivity among REC, mock-transfected REC, E1a, and combined E1a/ras transfectants. pEJ6.6ras, and combined ras/myc transfected pooled cellular populations demonstrated increases in radiation resistance when compared to the pooled radiobiologic data from untransfected and mock-transfected corresponding pooled cellular populations (p 2 , MID). Rat embryo cells, E1a, and mock-transfectants were relatively radiation sensitive and nontumorigenic. pE1a/ras was tumorigenic but demonstrated relatively low experimental metastatic potential. Ras, and ras/myc transfectants, demonstrated similar levels of experimental metastatic potential on lung colonization assays

  5. Safety Evaluation of Cosmetic Ingredients Regarding Their Skin Sensitization Potential

    Directory of Open Access Journals (Sweden)

    Winfried Steiling

    2016-03-01

    Full Text Available Up to today, product safety evaluation in the EU is predominantly based on data/information on their individual ingredients. Consequently, the quality and reliability of individual ingredient data is of vital interest. In this context, the knowledge about skin sensitization potential is an explicit need for both hazard and risk assessment. Proper skin sensitization data of the individual chemicals is essential, especially when dermal contact is intended, like for cosmetics. In some cases, e.g., in the presence of irritating chemicals, the combination of individual ingredients may also need to be evaluated to cover possible mixture effects. Today, it seems unlikely or even impossible that skin sensitization in humans can be adequately described by a single test result or even by a simple combination of a few data points (in vivo or in vitro. It is becoming evident that a set of data (including human data and market data and knowledge about the ingredient’s specific sensitizing potency needs to be taken into account to enable a reliable assessment of skin sensitization. A more in-depth understanding on mechanistic details of the Adverse-Outcome-Pathway of skin sensitization could contribute key data for a robust conclusion on skin sensitization.

  6. Forage Potential of Photoperiod-Sensitive millet ( Pennisetum ...

    African Journals Online (AJOL)

    To determine its potential as an annual forage, 'Maiwa', which is a short-day photoperiod-sensitive millet (Pennisetum americanum (Linn.) ... Improvement in the level and seasonal distribution of 'maiwa' herbage production as well as quality can be realised through suitable agronomic practices as well as breeding.

  7. Recording membrane potential changes through photoacoustic voltage sensitive dye

    DEFF Research Database (Denmark)

    Zhang, Haichong K.; Kang, Jeeun; Yan, Ping

    2017-01-01

    Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo...... systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching...... the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize...

  8. Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine.

    Science.gov (United States)

    Parkinson, J A; Olmstead, M C; Burns, L H; Robbins, T W; Everitt, B J

    1999-03-15

    Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.

  9. Listening to membrane potential: photoacoustic voltage-sensitive dye recording

    Science.gov (United States)

    Zhang, Haichong K.; Yan, Ping; Kang, Jeeun; Abou, Diane S.; Le, Hanh N. D.; Jha, Abhinav K.; Thorek, Daniel L. J.; Kang, Jin U.; Rahmim, Arman; Wong, Dean F.; Boctor, Emad M.; Loew, Leslie M.

    2017-04-01

    Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluorescence changes in response to neuronal or muscle electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a near-infrared photoacoustic VSD (PA-VSD), whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.

  10. Recording membrane potential changes through photoacoustic voltage sensitive dye

    Science.gov (United States)

    Zhang, Haichong K.; Kang, Jeeun; Yan, Ping; Abou, Diane S.; Le, Hanh N. D.; Thorek, Daniel L. J.; Kang, Jin U.; Gjedde, Albert; Rahmim, Arman; Wong, Dean F.; Loew, Leslie M.; Boctor, Emad M.

    2017-03-01

    Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. Based on this concept, we synthesized a novel near infrared photoacoustic VSD (PA-VSD) whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. With a 3-9 μM VSD concentration, we measured a PA signal increase in the range of 5.3 % to 18.1 %, and observed a corresponding signal reduction in fluorescence emission of 30.0 % to 48.7 %. A theoretical model successfully accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize the characteristics of improved photoacoustic probes. Together, our results demonstrate photoacoustic sensing as a potential new modality for sub-second recording and external imaging of electrophysiological and neurochemical events in the brain.

  11. Apoptotic potential and cell sensitivity to fractionated radiotherapy

    International Nuclear Information System (INIS)

    Rupnow, Brent A.; Murtha, Albert D.; Alarcon, Rodolfo M.; Giaccia, Amato J.; Knox, Susan J.

    1997-01-01

    irradiation resulted in decreased clonogenic survival of Rat-1MycER cells compared to cells treated without c-MycER activation following single doses of radiation from 0 to 10 Gy. The increased radiosensitivity conferred by c-Myc activation was suppressed by Bcl-2 overexpression, suggesting that c-Myc-mediated alterations in clonogenic survival are a result of altered apoptotic potential. While the difference in survival was only 1.22-fold following a single 2 Gy dose between Rat-1MycER cells treated in the presence and absence of c-MycER activation, treatment with 5 fractions of 2 Gy at 12 hour intervals resulted in a 2.99-fold decrease in clonogenic survival. Treatment of cells with 5 fractions of 4 Gy resulted in a 16.4-fold difference in clonogenic survival between cells with activated c-MycER and identical cells with inactive c-MycER, while the difference in survival was only 1.60-fold following a single 4 Gy dose. Bcl-2 overexpression was able to suppress c-Myc-mediated alterations in clonogenic survival following treatment with fractionated radiation. Conclusions: These results argue that increasing the sensitivity of cells to radiation-induced apoptosis can decrease their clonogenic survival in vitro. Furthermore, even small apoptosis-dependent differences in survival following single, small fractions of radiation may result in substantial differences in survival following multiple fractions of radiation. Experiments using Rat-1MycER derived tumor xenografts to test the effects of c-Myc-mediated alterations in apoptotic sensitivity on tumor growth delay following single dose and fractionated radiotherapy, in vivo, are in progress and will be discussed

  12. Locomotor training improves premotoneuronal control after chronic spinal cord injury.

    Science.gov (United States)

    Knikou, Maria; Mummidisetty, Chaithanya K

    2014-06-01

    Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking. Copyright © 2014 the American Physiological Society.

  13. Sensitivity of direct global warming potentials to key uncertainties

    International Nuclear Information System (INIS)

    Weubbles, D.J.; Jain, A.K.; Palten, K.O.; Grant, K.E.

    1995-01-01

    The concept of global warming potential was developed as a relative measure of the potential effects on climate of a greenhouse gas. In this paper a series of sensitivity studies examines several uncertainties in determination of Global Warming Potentials (GWPs). The original evaluation of GWPs did not attempt to account for the possible sinks of carbon dioxide (CO 2 ) that could balance the carbon cycle and produce atmospheric concentrations of CO 2 that match observations. In this study, a balanced carbon cycle model is applied in calculation of the radiative forcing from CO 2 . Use of the balanced model produces up to 21% enhancement of the GWPs for most trace gases compared with the IPCC (1990) values for time horizons up to 100 years, but a decreasing enhancement with longer time horizons. Uncertainty limits of the fertilization feedback parameter contribute a 20% range in GWP values. Another systematic uncertainty in GWPs is the assumption of an equilibrium atmosphere (one in which the concentration of trace gases remains constant) versus a disequilibrium atmosphere (one in which the concentration of trace gases varies with time). The latter gives GWPs that are 19 to 32% greater than the former for a 100 year time horizons, depending upon the carbon dioxide emission scenario chosen. Five scenarios are employed: constant-concentration, constant-emission past 1990 and the three IPCC (1992) emission scenarios. For the analysis of uncertainties in atmospheric lifetime (tor) of the GWP changes in direct proportion to (tor) for short-lived gases, but to a lesser extent for gases with (tor) greater than the time horizontal for the GWP calculation. 40 refs., 7 figs., 13 tabs

  14. Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential

    International Nuclear Information System (INIS)

    Pucheu-Haston, Cherie M.; Copeland, Lisa B.; Vallanat, Beena; Boykin, Elizabeth; Ward, Marsha D.W.

    2010-01-01

    Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in naive individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of ∼ 100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1 increased from 6-24 h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.

  15. An in vitro human skin test for assessing sensitization potential.

    Science.gov (United States)

    Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

    2016-05-01

    Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Sensitivity of direct global warming potentials to key uncertainties

    International Nuclear Information System (INIS)

    Wuebbles, D.J.; Patten, K.O.; Grant, K.E.; Jain, A.K.

    1992-07-01

    A series of sensitivity studies examines the effect of several uncertainties in Global Wanning Potentials (GWPs). For example, the original evaluation of GWPs for the Intergovernmental Panel on Climate Change (EPCC, 1990) did not attempt to account for the possible sinks of carbon dioxide (CO 2 ) that could balance the carbon cycle and produce atmospheric concentrations of C0 2 that match observations. In this study, a balanced carbon cycle model is applied in calculation of the radiative forcing from C0 2 . Use of the balanced model produces up to 20 percent enhancement of the GWPs for most trace gases compared with the EPCC (1990) values for time horizons up to 100 years, but a decreasing enhancement with longer time horizons. Uncertainty limits of the fertilization feedback parameter contribute a 10 percent range in GWP values. Another systematic uncertainty in GWPs is the assumption of an equilibrium atmosphere (one in which the concentration of trace gases remains constant) versus a disequilibrium atmosphere. The latter gives GWPs that are 15 to 30 percent greater than the former, dependening upon the carbon dioxide emission scenario chosen. Seven scenarios are employed: constant emission past 1990 and the six EPCC (1992) emission scenarios. For the analysis of uncertainties in atmospheric lifetime (τ), the GWP changes in direct proportion to τ for short-lived gases, but to a lesser extent for gases with τ greater than the time horizon for the GWP calculation

  17. The potential effectiveness of nanoparticles as radio sensitizers for radiotherapy

    Directory of Open Access Journals (Sweden)

    Mohammad Babaei

    2014-03-01

    Full Text Available Introduction: Application of nanoparticles as radio sensitizer is a promising field to improve efficiency of radiotherapy.Methods:This study was conducted to review nano radio sensitizers. PubMed, Ovid Medline, Science Direct, Scopus, ISI web of knowledge, and Springer databases were searched from 2000 to May 2013 to identify relevant studies. Search was restricted to English language. Results: We included any study that evaluated nanoparticles, volunteer of radio enhancement at radiotherapy on animals or cell lines. Nanoparticles can increase radio sensitivity of tumor cells. This effect was shown in vivo and in vitro, at kilovltage or megavoltage energies, in 24 reviewed studies. Focus of studies was on gold nanoparticles. Radio sensitizing effects of nanoparticles depend on nanoparticles’ size, type, concentration, intracellular localization, used irradiation energy and tested cell line.Conclusion: Literature suggests potency of nanoparticles for increasing cell radio sensitivity. Reviewed results are promising and warrant future clinical trials.

  18. Dermal Sensitization Potential of Triethyleneglycol Dinitrate (TEGDN) in Guinea Pigs

    Science.gov (United States)

    1989-01-01

    mutagenicity assay, acute oral toxicity tests in rats and mice, acute dermal toxicity in rabbits, dermal and ocular irritation studies in rabbits, and...conditions: 85E0102 had diffuse tracheitis, mild endocarditis , mild hepatitis, and diffuse pigment granules in the small intestine; 85E0103 had mild...severe ulceration progressing to necrosis. Sensitization is manifested as indirect inflammation mediated by components of the immune system in

  19. Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules.

    Directory of Open Access Journals (Sweden)

    Konda Leela Sarath Kumar

    Full Text Available Skin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage.The key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with 'High' reliability scoring, DEREK (accuracy = 72.73% and CCR = 71.44% and TOPKAT (accuracy = 60.00% and CCR = 61.67%. Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%, the coverage was very low (only 10 out of 77 molecules were predicted reliably.Owing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre-screening their molecules, and reducing time, cost and animal testing.

  20. Error signals driving locomotor adaptation

    DEFF Research Database (Denmark)

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo

    2016-01-01

    Locomotor patterns must be adapted to external forces encountered during daily activities. The contribution of different sensory inputs to detecting perturbations and adapting movements during walking is unclear. Here we examined the role of cutaneous feedback in adapting walking patterns to force...... walking (Choi et al. 2013). Sensory tests were performed to measure cutaneous touch threshold and perceptual threshold of force perturbations. Ankle movement were measured while subjects walked on the treadmill over three periods: baseline (1 min), adaptation (1 min) and post-adaptation (3 min). Subjects...

  1. Intestinal microflora as potential modifiers of sensitizer activity in vivo

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Clarke, C.; Dawson, K.B.; Simpson, W.; Simmons, D.J.C.

    1984-01-01

    Treatment of mice (some bearing Lewis lung tumors), with penicillin (PEN) at 500 mg/l drinking water for one week prior to treatment with misonidazole (MIS), resulted in: the elimination of their anaerobic cecal flora; a decrease in MIS-induced neurotoxicity; an increase in pharmacological exposure to MIS; a decrease in MIS chemopotentiation; a probable increase in MIS radiosensitization; an increase in MIS induced hypothermia. Assuming no chemical interaction between PEN and MIS, these observations indicate that the intestinal microflora can influence the activity of MIS in vivo. The observed reduction in the neurotoxic but not the radiosensitizing potential of MIS following PEN treatment indicates a therapeutic benefit

  2. Phytochemicals with radioprotection and radio-sensitizing potential

    Energy Technology Data Exchange (ETDEWEB)

    Tripathi, Yamini B., E-mail: yaminiok@yahoo.com [Dept. of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi (India)

    2012-07-01

    Ionizing radiation induces DNA damage and are harmful to mankind. They act through free radical generation, which target the double bonds of all cellular macromolecules. The radiation damage may be classified as probabilistic or deterministic, depending on the dose of radiation exposure. Since radiation affects multiple organs so those drugs which protect many organs, would be more beneficial. In this process herbal extracts, which are cocktail of several phyto-chemicals, would be more promising. Initially sulphur containing bio-molecules were identified as radio-protector, but now many secondary metabolites from plant kingdom, have been reported to be radio-protective. They have different mechanism of action, but most of them either prevent the FR induced DNA damage or accelerate the DNA repair process. Aminofostine, WR-2721, 159243, 2926 are some of the examples. However they have limited use because of associated cytotoxicity. Eicosanoids, topoisornerase inhibitors (e.g. camptothecin, topotecan), and the hypoxia-activated anthraquinone AQ4N have shown radioprotecting potential. Several plant products, derived from Tulsi, Vinca alkaloids, taxans, turmeric, Rubia cordifolia, Semecarpus anacardium and several plants rich in polyphenols and flavones have shown hemotherapeutic potential. Similarly, Hippophae, rhodiola imbricata, Podophyllum hexandrum, Ocimum sancturn, Plumbago zeylanica etc have shown radioprotection. Rubia cordifolia has shown both chemotherapeutic and radioprotective property in rats and A-431 cells. Similarly Semecarpus anacardium extract has shown cell cycle arrest in DU-145 cells. (author)

  3. Phytochemicals with radioprotection and radio-sensitizing potential

    International Nuclear Information System (INIS)

    Tripathi, Yamini B.

    2012-01-01

    Ionizing radiation induces DNA damage and are harmful to mankind. They act through free radical generation, which target the double bonds of all cellular macromolecules. The radiation damage may be classified as probabilistic or deterministic, depending on the dose of radiation exposure. Since radiation affects multiple organs so those drugs which protect many organs, would be more beneficial. In this process herbal extracts, which are cocktail of several phyto-chemicals, would be more promising. Initially sulphur containing bio-molecules were identified as radio-protector, but now many secondary metabolites from plant kingdom, have been reported to be radio-protective. They have different mechanism of action, but most of them either prevent the FR induced DNA damage or accelerate the DNA repair process. Aminofostine, WR-2721, 159243, 2926 are some of the examples. However they have limited use because of associated cytotoxicity. Eicosanoids, topoisornerase inhibitors (e.g. camptothecin, topotecan), and the hypoxia-activated anthraquinone AQ4N have shown radioprotecting potential. Several plant products, derived from Tulsi, Vinca alkaloids, taxans, turmeric, Rubia cordifolia, Semecarpus anacardium and several plants rich in polyphenols and flavones have shown hemotherapeutic potential. Similarly, Hippophae, rhodiola imbricata, Podophyllum hexandrum, Ocimum sancturn, Plumbago zeylanica etc have shown radioprotection. Rubia cordifolia has shown both chemotherapeutic and radioprotective property in rats and A-431 cells. Similarly Semecarpus anacardium extract has shown cell cycle arrest in DU-145 cells. (author)

  4. Genetic deletion of GPR52 enhances the locomotor-stimulating effect of an adenosine A2A receptor antagonist in mice: A potential role of GPR52 in the function of striatopallidal neurons.

    Science.gov (United States)

    Nishiyama, Keiji; Suzuki, Hirobumi; Maruyama, Minoru; Yoshihara, Tomoki; Ohta, Hiroyuki

    2017-09-01

    G protein-coupled receptor 52 (GPR52) is largely co-expressed with dopamine D 2 receptor (DRD2) in the striatum and nucleus accumbens, and this expression pattern is similar to that of adenosine A 2A receptor (ADORA2A). GPR52 has been proposed as a therapeutic target for positive symptoms of schizophrenia, based on observations from pharmacological and transgenic mouse studies. However, the physiological role of GPR52 in dopaminergic functions in the basal ganglia remains unclear. Here, we used GPR52 knockout (KO) mice to examine the role of GPR52 in dopamine receptor-mediated and ADORA2A-mediated locomotor activity and dopamine receptor signaling. High expression of GPR52 protein in the striatum, nucleus accumbens, and lateral globus pallidus of wild type (WT) littermates was confirmed by immunohistochemical analysis. GPR52 KO and WT mice exhibited almost identical locomotor responses to the dopamine releaser methamphetamine and the N-methyl-d-aspartate antagonist MK-801. In contrast, the locomotor response to the ADORA2A antagonist istradefylline was significantly augmented in GPR52 KO mice compared to WT mice. Gene expression analysis revealed that striatal expression of DRD2, but not of dopamine D 1 receptor and ADORA2A, was significantly decreased in GPR52 KO mice. Moreover, a significant reduction in the mRNA expression of enkephalin, a marker of the activity of striatopallidal neurons, was observed in the striatum of GPR52 KO mice, suggesting that GPR52 deletion could enhance DRD2 signaling. Taken together, these results imply the physiological relevance of GPR52 in modulating the function of striatopallidal neurons, possibly by interaction of GPR52 with ADORA2A and DRD2. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Woodlouse locomotor behavior in the assessment of clean and contaminated field sites

    Energy Technology Data Exchange (ETDEWEB)

    Bayley, M.; Baatrup, E. [Aarhus Univ. (Denmark). Inst. of Biological Sciences; Bjerregaard, P. [Odense Univ. (Denmark). Inst. of Biology

    1997-11-01

    Specimens of the woodlouse Oniscus asellus were collected at four clean field sites and from a recently closed iron foundry heavily contaminated with zinc, lead, chromium, and nickel. Each of the 30 woodlice per group was housed individually and acclimatized to laboratory conditions for 2 d on a humid plaster of paris substrate. Thereafter, the locomotor behavior of each animal was measured for 4 h employing automated computer-aided video tracking. Linear discriminant analysis of five locomotor parameters revealed average velocity and path length as the principle components separating the polluted site and control animals. Post hoc analysis of the discriminant variable for animals from all five sites showed that the animals from the polluted site where significantly hyperactive when compared to all controls. Further, control animals collected from sites separated by several hundred kilometers were remarkably similar in their locomotor behavior. This preliminary study highlights the potential utility of quantitative analysis of animal locomotor behavior in environmental monitoring.

  6. Evaluation of human skin tests for potential dermal irritant and contact sensitizing products: a position paper

    NARCIS (Netherlands)

    Loveren H van; Jong WH de; Garssen J; LPI

    1998-01-01

    Prediction of human cutaneous irritation and sensitization in view of hazard identification has primarily relied on the use of laboratory animals. Such studies in laboratory animals have been very instrumental in the detection of potential contact sensitizing agents. There are however many

  7. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

    Science.gov (United States)

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2016-02-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PsycINFO Database Record (c) 2016 APA, all rights reserved.

  8. Classification of sensitizing and irritative potential in a combined in-vitro assay

    International Nuclear Information System (INIS)

    Wanner, Reinhard; Sonnenburg, Anna; Quatchadze, Maria; Schreiner, Maximilian; Peiser, Matthias; Zuberbier, Torsten; Stahlmann, Ralf

    2010-01-01

    We have developed a coculture system which in parallel indicates the sensitizing and irritative potential of xenobiotics. The assay is named loose-fit coculture-based sensitization assay (LCSA) and may be performed within 5 days. The system is composed of human monocytes that differentiate to a kind of dendritic cells by 2-day culturing in the presence of allogenic keratinocytes. The culture medium is enriched by a cocktail of recombinant cytokines. On day 3, concentration series of probes are added. On day 5, cells are harvested and analyzed for expression range of CD86 as a marker of sensitizing potential and for uptake of the viability stain 7-AAD as a marker of irritative potential. Estimation of the concentration required to cause a half-maximal increase in CD86 expression allowed quantification of sensitizing potential, and estimation of the concentration required to reduce viability to 50% allowed quantification of irritative potential. Examination of substances with known potential resulted in categorization of test scores. To evaluate our data, we have compared results with those of the validated animal-based sensitization test, the murine local lymph node assay (LLNA, OECD TG 429). To a large extent, results from LCSA and from LLNA achieved analogous grouping of allergens into categories like weak-moderate-strong. However, the new assay showed an improved capacity to distinguish sensitizers from non-sensitizers and irritants. In conclusion, the LCSA contains potential to fulfil the requirements of the EU's programme for the safety of chemicals 'Registration, Evaluation, Authorisation and Restriction of chemical substances' (REACH, 2006) to replace animal models.

  9. Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

    Science.gov (United States)

    Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

    2013-12-01

    Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

  10. A stochastic locomotor control model for the nurse shark, Ginglymostoma cirratum.

    Science.gov (United States)

    Gerald, K B; Matis, J H; Kleerekoper, H

    1978-06-12

    The locomotor behavior of the nurse shark (Ginglymostoma cirratum) is characterized by 17 variables (frequency and ratios of left, right, and total turns; their radians; straight paths (steps); distance travelled; and velocity) Within each of these variables there is an internal time dependency the structure of which was elaborated together with an improved statistical model predicting their behavior within 90% confidence limits. The model allows for the sensitive detection of subtle locomotor response to sensory stimulation as values of variables may exceed the established confidence limits within minutes after onset of the stimulus. The locomotor activity is well described by an autoregression time series model and can be predicted by only seven variables. Six of these form two independently operating clusters. The first one consists of: the number of right turns, the distance travelled and the mean velocity; the second one of: the mean size of right turns, of left turns, and of all turns. The same clustering is obtained independently by a cluster analysis of cross-sections of the seven time series. It is apparent that, among a total of 17 locomotor variables, seven behave as individually independent agents, presumably controlled by seven separate and independent centers. The output of each center can only be predicted by its own behavior. In spite of the individual of the seven variables, their internal structure is similar in important aspects which may result from control by a common command center. The shark locomotor model differs in important aspects from the previously constructed for the goldfish. The interdependence of the locomotor variables in both species may be related to the control mechanisms postulated by von Holst for the coordination of rhythmic fin movements in fishes. A locomotor control model for the nurse shark is proposed.

  11. On the sensitivity of nucleon-nucleon correlations to the form of short-range potential

    International Nuclear Information System (INIS)

    Gmitro, M.; Kvasil, J.; Lednicky, R.; Lyuboshitz, V.L.

    1986-01-01

    Nucleon-nucleon correlation characteristics are calculated for several phenomenological and realistic strong potentials. The results show that a square-well potential reasonably well approximates the nucleon-nucleon interaction if one calculates the correlations between nucleons generated in a region with an r.m.s. radius larger than 1.5-2 fm. Vice versa, the correlations of nucleons emitted from a smaller generation region are sensitive to the form of the assumed nucleon-nucleon potential. (author)

  12. Determination of aerodynamic sensitivity coefficients based on the three-dimensional full potential equation

    Science.gov (United States)

    Elbanna, Hesham M.; Carlson, Leland A.

    1992-01-01

    The quasi-analytical approach is applied to the three-dimensional full potential equation to compute wing aerodynamic sensitivity coefficients in the transonic regime. Symbolic manipulation is used to reduce the effort associated with obtaining the sensitivity equations, and the large sensitivity system is solved using 'state of the art' routines. Results are compared to those obtained by the direct finite difference approach and both methods are evaluated to determine their computational accuracy and efficiency. The quasi-analytical approach is shown to be accurate and efficient for large aerodynamic systems.

  13. Sensitivity of radiation methods of diagnosis of electric potentials in dielectric materials

    International Nuclear Information System (INIS)

    Sapozhkov, Yu.I.; Smekalin, L.F.; Yagushkin, N.I.

    1985-01-01

    On the base of the albedo method the characteristics of radiation methods of diagnosis of electric potentials inside dielectrics, such as sensitivity and resolution are considered. Investigations are carried out for electron energies of tens keV. It is shown that with energy growth the sensitivity to electric field in the dielectrics volume drops. The target atomic number growth reduces the sensitivity approximately 1/lnz. The albedo method resolution in the investigated energy range is constant. The results obtained testify to the usability radiation methods of the diagnosis for control of electric fields of dielectric structural materials in the course of their operation

  14. Sensitivity of the elastic scattering matrix elements to the range of the inelastic potentials

    International Nuclear Information System (INIS)

    Rawitscher, G.H.; Rasoanaivo, R.Y.

    1983-01-01

    The solution to a system of coupled equations is examined with regard to the effect of the long range part of the inelastic potentials upon the elastic phase shifts. It is found that those parts of the inelastic potentials which occur beyond the range of the elastic to inelastic transition potentials affect the elastic phase shifts in only a minor way. The proof is given theoretically by means of a Green's function formulation which includes the long range part of the inelastic potentials perturbatively. When applied to the calculation of the effect of breakup on the deuteron-nucleus elastic scattering, the argument confirms the finding that errors in the long range part of the potentials in the breakup channels do not sensitively affect the elastic deuteron scattering cross section. This result explains why the elastic scattering is not very sensitive to the choice of the discretization procedure of the breakup space

  15. Footwear and locomotor skill performance in preschoolers.

    Science.gov (United States)

    Robinson, Leah E; Rudisill, Mary E; Weimar, Wendi H; Breslin, Casey M; Shroyer, Justin F; Morera, Maria

    2011-10-01

    The effect of footwear on locomotor skill performance was examined. 12 children (4 boys, 8 girls; M age = 56.3 mo., SD = 3.3) served as participants. Participants were randomly assigned to perform the locomotor subscale of Ulrich's Test of Gross Motor Development in two shoe conditions (Condition 1: Stride Rite athletic shoes, and Condition 2: flip flop sandals). Children scored significantly higher when wearing athletic shoes than flip-flop sandals. This finding is relevant for motor performance and safety in physical education and movement programs.

  16. Sensitivity and Discovery Potential of CUORE to Neutrinoless Double-Beta Decay

    Energy Technology Data Exchange (ETDEWEB)

    Alessandria, F; Ardito, R; Artusa, DR; III, FTA; Azzolini, O; Balata, M; Banks, TI; Bari, G; Beeman, J; Bellini, F; Bersani, A; Biassoni, M; Bloxham, T; Brofferio, C; Bucci, C; Cai, XZ; Canonica, L; Cao, X; Capelli, S; Carbone, L; Cardani, L; Carrettoni, M; Casali, N; Chiesa, D; Chott, N; Clemenza, M; Cosmelli, C; Cremonesi, O; Creswick, RJ; Dafinei, I; Dally, A; Datskov, V; Biasi, AD; Deninno, MM; Domizio, SD; Vacri, MLD; Ejzak, L; Faccini, R; Fang, DQ; Farach, HA; Faverzani, M; Fernandes, G; Ferri, E; Ferroni, F; Fiorini, E; Franceschi, MA; Freedman, SJ; Fujikawa, BK; Giachero, A; Gironi, L; Giuliani, A; Goett, J; Gorla, P; Gotti, C; Guardincerri, E; Gutierrez, TD; Haller, EE; Han, K; Heeger, KM; Huang, HZ; Kadel, R; Kazkaz, K; Keppel, G; Kogler, L; Kolomensky, YG; Lenz, D; Li, YL; Ligi, C; Liu, X; Ma, YG; Maiano, C; Maino, M; Martinez, M; Maruyama, RH; Mei, Y; Moggi, N; Morganti, S; Napolitano, T; Newman, S; Nisi, S; Nones, C; Norman, EB; Nucciotti, A; O' Donnell, T; Orio, F; Orlandi, D; Ouellet, JL; Pallavicini, M; Palmieri, V; Pattavina, L; Pavan, M; Pedretti, M; Pessina, G; Piperno, G; Pirro, S; Previtali, E; Rampazzo, V; Rimondi, F; Rosenfeld, C; Rusconi, C; Sala, E; Sangiorgio, S; Scielzo, ND; Sisti, M; Smith, AR; Stivanello, F; Taffarello, L; Tenconi, M; Tian, WD; Tomei, C; Trentalange, S; Ventura, G; Vignati, M; Wang, BS; Wang, HW; Wise, T; Woodcraft, A; Zanotti, L; Zarra, C; Zhu, BX; Zucchelli, S

    2017-07-06

    We present a study of the sensitivity and discovery potential of CUORE, a bolometric double-beta decay experiment under construction at the Laboratori Nazionali del Gran Sasso in Italy. Two approaches to the computation of experimental sensitivity for various background scenarios are presented, and an extension of the sensitivity formulation to the discovery potential case is also discussed. Assuming a background rate of 10-2 cts/(keV kg y), we find that, after 5 years of live time, CUORE has a 1 sigma sensitivity to the neutrinoless double-beta decay half-life of T$0v\\atop{1/2}$(1θ) = 1.6 \\times 1026 y and thus a potential to probe the effective Majorana neutrino mass down to 40-100 meV; the sensitivity at 1.64 sigma, which corresponds to 90% C.L., will be T$0v\\atop{1/2}$(1.64θ) = 9.5 \\times 1025 y. This range is compared with the claim of observation of neutrinoless double-beta decay in 76Ge and the preferred range of the neutrino mass parameter space from oscillation results.

  17. A simple in chemico method for testing skin sensitizing potential of chemicals using small endogenous molecules.

    Science.gov (United States)

    Nepal, Mahesh Raj; Shakya, Rajina; Kang, Mi Jeong; Jeong, Tae Cheon

    2018-06-01

    Among many of the validated methods for testing skin sensitization, direct peptide reactivity assay (DPRA) employs no cells or animals. Although no immune cells are involved in this assay, it reliably predicts the skin sensitization potential of a chemical in chemico. Herein, a new method was developed using endogenous small-molecular-weight compounds, cysteamine and glutathione, rather than synthetic peptides, to differentiate skin sensitizers from non-sensitizers with an accuracy as high as DPRA. The percent depletion of cysteamine and glutathione by test chemicals was measured by an HPLC equipped with a PDA detector. To detect small-size molecules, such as cysteamine and glutathione, a derivatization by 4-(4-dimethylaminophenylazo) benzenesulfonyl chloride (DABS-Cl) was employed prior to the HPLC analysis. Following test method optimization, a cut-off criterion of 7.14% depletion was applied to differentiate skin sensitizers from non-sensitizers in combination of the ratio of 1:25 for cysteamine:test chemical with 1:50 for glutathione:test chemical for the best predictivity among various single or combination conditions. Although overlapping HPLC peaks could not be fully resolved for some test chemicals, high levels of sensitivity (100.0%), specificity (81.8%), and accuracy (93.3%) were obtained for 30 chemicals tested, which were comparable or better than those achieved with DPRA. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Neuronal control of locomotor handedness in Drosophila.

    Science.gov (United States)

    Buchanan, Sean M; Kain, Jamey S; de Bivort, Benjamin L

    2015-05-26

    Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality.

  19. Sensitivity of the International Skating Union's Mathematical Criteria to Flag Potential Scoring Anomalies

    Science.gov (United States)

    Looney, Marilyn A.; Howell, Steven M.

    2015-01-01

    This article describes the "mathematical criteria" employed by the International Skating Union (ISU) to identify potential judging anomalies within competitive figure skating. The mathematical criteria have greater sensitivity to identify scoring anomalies for technical element scores than for the program component scores. This article…

  20. Sensitivity of the amplitude of the single muscle fibre action potential to microscopic volume conduction parameters

    NARCIS (Netherlands)

    Alberts, B.A.; Rutten, Wim; Wallinga, W.; Boom, H.B.K.

    1988-01-01

    A microscopic model of volume conduction was applied to examine the sensitivity of the single muscle fibre action potential to variations in parameters of the source and of the volume conductor, such as conduction velocity, intracellular conductivity and intracellular volume fraction. The model

  1. An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

    Science.gov (United States)

    Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

    2017-01-01

    We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

  2. Off-shell sensitivity, repulsive correlations and the pion-nucleus optical potential

    Energy Technology Data Exchange (ETDEWEB)

    Keister, B D [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA). Dept. of Physics

    1977-07-01

    Repulsive nucleon-nucleon correlations tend to reduce the dependence of pion-nucleus elastic scattering upon the off-shell pion-nucleon dynamics. However, optical potential calculations can in practice be quite sensitive to the particular choice of off-shell model parameters. It is argued that this sensitivity results from the nature of the optical potential as a one-body operator which introduces extra off-shell dependence not found in physical many-body process itself. Thus, one must be very careful in any attempt to extract correlation or off-shell information, or to predict pion-nucleus phase shifts, by means of an optical potential theory. Results of model calculations are presented for purposes of illustration.

  3. Parametric sensitivity analysis for the helium dimers on a model potential

    Directory of Open Access Journals (Sweden)

    Nelson Henrique Teixeira Lemes

    2012-01-01

    Full Text Available Potential parameters sensitivity analysis for helium unlike molecules, HeNe, HeAr, HeKr and HeXe is the subject of this work. Number of bound states these rare gas dimers can support, for different angular momentum, will be presented and discussed. The variable phase method, together with the Levinson's theorem, is used to explore the quantum scattering process at very low collision energy using the Tang and Toennies potential. These diatomic dimers can support a bound state even for relative angular momentum equal to five, as in HeXe. Vibrational excited states, with zero angular momentum, are also possible for HeKr and HeXe. Results from sensitive analysis will give acceptable order of magnitude on potentials parameters.

  4. The number of postsynaptic currents necessary to produce locomotor- related cyclic information in neurons in the neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Raastad, Morten; Johnson, Bruce R.; Kiehn, Ole

    1996-01-01

    To understand better how synaptic signaling contributes to network activity, we analyzed the potential contribution of putative unitary postsynaptic currents (PSCs) to locomotor-related information received by spinal interneurons in neonatal rats. The average cyclic modulation of the whole-cell c......-5) of the synapses contributing to the cyclic information need to be active simultaneously. This suggests that individual presynaptic cells in a central locomotor network can have a powerful influence on other neurons....

  5. Using a Split-belt Treadmill to Evaluate Generalization of Human Locomotor Adaptation.

    Science.gov (United States)

    Vasudevan, Erin V L; Hamzey, Rami J; Kirk, Eileen M

    2017-08-23

    Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. However, studying human locomotor learning can be challenging. During infancy and childhood, the neuromuscular system is quite immature, and it is unlikely that locomotor learning during early stages of development is governed by the same mechanisms as in adulthood. By the time humans reach maturity, they are so proficient at walking that it is difficult to come up with a sufficiently novel task to study de novo locomotor learning. The split-belt treadmill, which has two belts that can drive each leg at a different speed, enables the study of both short- (i.e., immediate) and long-term (i.e., over minutes-days; a form of motor learning) gait modifications in response to a novel change in the walking environment. Individuals can easily be screened for previous exposure to the split-belt treadmill, thus ensuring that all experimental participants have no (or equivalent) prior experience. This paper describes a typical split-belt treadmill adaptation protocol that incorporates testing methods to quantify locomotor learning and generalization of this learning to other walking contexts. A discussion of important considerations for designing split-belt treadmill experiments follows, including factors like treadmill belt speeds, rest breaks, and distractors. Additionally, potential but understudied confounding variables (e.g., arm movements, prior experience) are considered in the discussion.

  6. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Avonto, Cristina; Chittiboyina, Amar G. [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Rua, Diego [The Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD 20740 (United States); Khan, Ikhlas A., E-mail: ikhan@olemiss.edu [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States)

    2015-12-01

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

  7. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    International Nuclear Information System (INIS)

    Avonto, Cristina; Chittiboyina, Amar G.; Rua, Diego; Khan, Ikhlas A.

    2015-01-01

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

  8. Evaluation of the Potential Sensitization of Chlorogenic Acid: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mingbao Lin

    2013-01-01

    Full Text Available Chlorogenic acid (CGA widely exists in many plants, which are used as medicinal substances in traditional Chinese medicine injectables (TCMIs that have been widely applied in clinical treatments. However, it is still controversial whether CGA is responsible for TCMIs-related hypersensitivity. Several studies have been performed to evaluate its potential sensitization property, but the results were inconclusive. Therefore, the aim of this study was to evaluate its potential sensitization systematically using meta-analysis based on data extracted from literatures, searching databases of PubMed, EMBASE, ISI Web of Knowledge, CNKI, VIP, and CHINAINFO from January 1979 to October 2012, a total of 108 articles were retrieved by electronic search strategy, out of which 13 studies met the inclusion criteria. In ASA test, odds ratio of behavior changes was 4.33 (1.62, 11.60, showing significant changes after CGA treatment (P=0.004. Serum IgG, serum histamine, PLN cellularity, and IgG1 AFCs were significantly enhanced after CGA treatment (P<0.05. Totally, these results indicated that CGA could induce a positive reaction in potential sensitization, and intravenous administration of it might be a key factor for sensitization triggering, which could at least warrant more careful application of TCMIs containing CGA in clinical practices.

  9. Potential development in dye-sensitized solar cells for renewable energy

    CERN Document Server

    Pandikumar, Alagarsamy

    2013-01-01

    The development of photovoltaic technology is expected to solve problems related to energy shortages and environmental pollution caused by the use of fossil fuels. Dye-sensitizedsolar cells (DSSCs) are promising next-generation alternatives to conventional silicon-based photovoltaic devices owing to their low manufacturing cost and potentially high conversion efficiency. This special topic volume addresses recent advances in the research on dye-sensitized solar cells. The focus of this special topic volume is on materials development (sensitizers, nanostructured oxide films, and electrolyte),

  10. Exploring the potential of context-sensitive CADe in screening mammography

    International Nuclear Information System (INIS)

    Tourassi, Georgia D.; Mazurowski, Maciej A.; Harrawood, Brian P.; Krupinski, Elizabeth A.

    2010-01-01

    Purpose: Conventional computer-assisted detection (CADe) systems in screening mammography provide the same decision support to all users. The aim of this study was to investigate the potential of a context-sensitive CADe system which provides decision support guided by each user's focus of attention during visual search and reporting patterns for a specific case. Methods: An observer study for the detection of malignant masses in screening mammograms was conducted in which six radiologists evaluated 20 mammograms while wearing an eye-tracking device. Eye-position data and diagnostic decisions were collected for each radiologist and case they reviewed. These cases were subsequently analyzed with an in-house knowledge-based CADe system using two different modes: Conventional mode with a globally fixed decision threshold and context-sensitive mode with a location-variable decision threshold based on the radiologists' eye dwelling data and reporting information. Results: The CADe system operating in conventional mode had 85.7% per-image malignant mass sensitivity at 3.15 false positives per image (FPsI). The same system operating in context-sensitive mode provided personalized decision support at 85.7%-100% sensitivity and 0.35-0.40 FPsI to all six radiologists. Furthermore, context-sensitive CADe system could improve the radiologists' sensitivity and reduce their performance gap more effectively than conventional CADe. Conclusions: Context-sensitive CADe support shows promise in delineating and reducing the radiologists' perceptual and cognitive errors in the diagnostic interpretation of screening mammograms more effectively than conventional CADe.

  11. Myeloid differentiation-2 is a potential biomarker for the amplification process of allergic airway sensitization in mice

    Directory of Open Access Journals (Sweden)

    Daisuke Koyama

    2015-09-01

    Conclusions: Our data suggest MD-2 is a critical regulator of the establishment of allergic airway sensitization to HDM in mice. Serum MD-2 may represent a potential biomarker for the amplification of allergic sensitization and allergic inflammation.

  12. Neuromodulation of the lumbar spinal locomotor circuit.

    Science.gov (United States)

    AuYong, Nicholas; Lu, Daniel C

    2014-01-01

    The lumbar spinal cord contains the necessary circuitry to independently drive locomotor behaviors. This function is retained following spinal cord injury (SCI) and is amenable to rehabilitation. Although the effectiveness of task-specific training and pharmacologic modulation has been repeatedly demonstrated in animal studies, results from human studies are less striking. Recently, lumbar epidural stimulation (EDS) along with locomotor training was shown to restore weight-bearing function and lower-extremity voluntary control in a chronic, motor-complete human SCI subject. Related animal studies incorporating EDS as part of the therapeutic regiment are also encouraging. EDS is emerging as a promising neuromodulatory tool for SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Chromatic spatial contrast sensitivity estimated by visual evoked cortical potential and psychophysics

    Science.gov (United States)

    Barboni, M.T.S.; Gomes, B.D.; Souza, G.S.; Rodrigues, A.R.; Ventura, D.F.; Silveira, L.C.L.

    2013-01-01

    The purpose of the present study was to measure contrast sensitivity to equiluminant gratings using steady-state visual evoked cortical potential (ssVECP) and psychophysics. Six healthy volunteers were evaluated with ssVECPs and psychophysics. The visual stimuli were red-green or blue-yellow horizontal sinusoidal gratings, 5° × 5°, 34.3 cd/m2 mean luminance, presented at 6 Hz. Eight spatial frequencies from 0.2 to 8 cpd were used, each presented at 8 contrast levels. Contrast threshold was obtained by extrapolating second harmonic amplitude values to zero. Psychophysical contrast thresholds were measured using stimuli at 6 Hz and static presentation. Contrast sensitivity was calculated as the inverse function of the pooled cone contrast threshold. ssVECP and both psychophysical contrast sensitivity functions (CSFs) were low-pass functions for red-green gratings. For electrophysiology, the highest contrast sensitivity values were found at 0.4 cpd (1.95 ± 0.15). ssVECP CSF was similar to dynamic psychophysical CSF, while static CSF had higher values ranging from 0.4 to 6 cpd (P chromatic functions showed no specific tuning shape; however, at high spatial frequencies the evoked potentials showed higher contrast sensitivity than the psychophysical methods (P chromatic red-green CSFs in agreement with psychophysical thresholds, mainly if the same temporal properties are applied to the stimulus. For blue-yellow CSF, correlation between electrophysiology and psychophysics was poor at high spatial frequency, possibly due to a greater effect of chromatic aberration on this kind of stimulus. PMID:23369980

  14. A case study for evaluating potential soil sensitivity in aridland systems.

    Science.gov (United States)

    Peterman, Wendy L; Ferschweiler, Ken

    2016-04-01

    Globally, ecosystems are subjected to prolonged droughts and extreme heat events, leading to forest die-offs and dominance shifts in vegetation. Some scientists and managers view soil as the main resource to be considered in monitoring ecosystem responses to aridification. As the medium through which precipitation is received, stored, and redistributed for plant use, soil is an important factor in the sensitivity of ecosystems to a drying climate. This study presents a novel approach to evaluating where on a landscape soils may be most sensitive to drying, making them less resilient to disturbance, and where potential future vegetation changes could lead to such disturbance. The drying and devegetation of arid lands can increase wind erosion, contributing to aerosol and dust emissions. This has implications for air quality, human health, and water resources. This approach combines soil data with vegetation simulations, projecting future vegetation change, to create maps of potential areas of concern for soil sensitivity and dust production in a drying climate. Consistent with recent observations, the projections show shifts from grasslands and woodlands to shrublands in much of the southwestern region. An increase in forested area occurs, but shifts in the dominant types and spatial distribution of the forests also are seen. A net increase in desert ecosystems in the region and some changes in alpine and tundra ecosystems are seen. Approximately 124,000 km(2) of soils flagged as "sensitive" are projected to have vegetation change between 2041 and 2050, and 82,927 km(2) of soils may become sensitive because of future vegetation changes. These maps give managers a way to visualize and identify where soils and vegetation should be investigated and monitored for degradation in a drying climate, so restoration and mitigation strategies can be focused in these areas. © 2015 SETAC.

  15. Identification of a compound isolated from German chamomile (Matricaria chamomilla) with dermal sensitization potential

    International Nuclear Information System (INIS)

    Avonto, Cristina; Rua, Diego; Lasonkar, Pradeep B.; Chittiboyina, Amar G.; Khan, Ikhlas A.

    2017-01-01

    German chamomile is one of the most popular herbal ingredients used in cosmetics and personal care products. Allergic skin reactions following topical application of German chamomile have been occasionally reported, although it is not fully understood which of the chemical constituents is responsible for this adverse effect. In the present work, three candidate sensitizers were isolated from German chamomile based on activity-guided fractionation of chamomile extracts tested using the in vitro KeratinoSens™ assay. The compounds were identified as the polyacetylene tonghaosu (1), and both trans- and cis-glucomethoxycinnamic acids (2 and 3). These three compounds were classified as non- to weakly reactive using in chemico methods; however, aged tonghaosu was found to be more reactive when compared to freshly isolated tonghaosu. The polyacetylene (1) constituent was determined to be chemically unstable, generating a small electrophilic spirolactone, 1,6-dioxaspiro[4.4]non-3-en-2-one (4), upon aging. This small lactone (4) was strongly reactive in both in chemico HTS- and NMR-DCYA methods and further confirmed as a potential skin sensitizer by Local Lymph Node Assay (LLNA). - Highlights: • Fractions of German chamomile tested positive in the KeratinoSens™ assay. • Three compounds containing structural alerts were isolated and tested with in chemico methods. • The polyacetylene tonghaosu was found to be unstable and categorized as potential pre-hapten. • A degradation product of tonghaosu tested as positive dermal sensitizer in animal studies.

  16. Identification of a compound isolated from German chamomile (Matricaria chamomilla) with dermal sensitization potential

    Energy Technology Data Exchange (ETDEWEB)

    Avonto, Cristina [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677 (United States); Rua, Diego [The Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD 20740 (United States); Lasonkar, Pradeep B.; Chittiboyina, Amar G. [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677 (United States); Khan, Ikhlas A., E-mail: ikhan@olemiss.edu [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677 (United States); Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, MS 38677 (United States)

    2017-03-01

    German chamomile is one of the most popular herbal ingredients used in cosmetics and personal care products. Allergic skin reactions following topical application of German chamomile have been occasionally reported, although it is not fully understood which of the chemical constituents is responsible for this adverse effect. In the present work, three candidate sensitizers were isolated from German chamomile based on activity-guided fractionation of chamomile extracts tested using the in vitro KeratinoSens™ assay. The compounds were identified as the polyacetylene tonghaosu (1), and both trans- and cis-glucomethoxycinnamic acids (2 and 3). These three compounds were classified as non- to weakly reactive using in chemico methods; however, aged tonghaosu was found to be more reactive when compared to freshly isolated tonghaosu. The polyacetylene (1) constituent was determined to be chemically unstable, generating a small electrophilic spirolactone, 1,6-dioxaspiro[4.4]non-3-en-2-one (4), upon aging. This small lactone (4) was strongly reactive in both in chemico HTS- and NMR-DCYA methods and further confirmed as a potential skin sensitizer by Local Lymph Node Assay (LLNA). - Highlights: • Fractions of German chamomile tested positive in the KeratinoSens™ assay. • Three compounds containing structural alerts were isolated and tested with in chemico methods. • The polyacetylene tonghaosu was found to be unstable and categorized as potential pre-hapten. • A degradation product of tonghaosu tested as positive dermal sensitizer in animal studies.

  17. Comparison of sensitivity of magnetic resonance imaging and evoked potentials in the detection of brainstem involvement in multiple sclerosis

    International Nuclear Information System (INIS)

    Comi, G.; Martinelli, V.; Medaglini, S.; Locatelli, T.; Magnani, G.; Poggi, A.; Triulzi, F.

    1988-01-01

    A comparison was made of the sensitivity of magnetic resonance imaging and the combined use of Brainstem Auditory Evoked Potential and Median Somatosensory Evoked Potential in the detection of brainstem dysfunction in 54 multiple sclerosis patients. 10 refs.; 2 tabs

  18. Application of the KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations.

    Science.gov (United States)

    Settivari, Raja S; Gehen, Sean C; Amado, Ricardo Acosta; Visconti, Nicolo R; Boverhof, Darrell R; Carney, Edward W

    2015-07-01

    Assessment of skin sensitization potential is an important component of the safety evaluation process for agrochemical products. Recently, non-animal approaches including the KeratinoSens™ assay have been developed for predicting skin sensitization potential. Assessing the utility of the KeratinoSens™ assay for use with multi-component mixtures such as agrochemical formulations has not been previously evaluated and is a significant need. This study was undertaken to evaluate the KeratinoSens™ assay prediction potential for agrochemical formulations. The assay was conducted for 8 agrochemical active ingredients (AIs) including 3 sensitizers (acetochlor, meptyldinocap, triclopyr), 5 non-sensitizers (aminopyralid, clopyralid, florasulam, methoxyfenozide, oxyfluorfen) and 10 formulations for which in vivo sensitization data were available. The KeratinoSens™ correctly predicted the sensitization potential of all the AIs. For agrochemical formulations it was necessary to modify the standard assay procedure whereby the formulation was assumed to have a common molecular weight. The resultant approach correctly predicted the sensitization potential for 3 of 4 sensitizing formulations and all 6 non-sensitizing formulations when compared to in vivo data. Only the meptyldinocap-containing formulation was misclassified, as a result of high cytotoxicity. These results demonstrate the promising utility of the KeratinoSens™ assay for evaluating the skin sensitization potential of agrochemical AIs and formulations. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

    Science.gov (United States)

    Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Hyeok Choi, Byeong; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon; Son, Sang Wook

    2011-07-01

    The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

  20. Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

    International Nuclear Information System (INIS)

    Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Choi, Byeong Hyeok; Son, Sang Wook; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon

    2011-01-01

    The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO 2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO 2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

  1. In vitro assessment of skin sensitization, photosensitization and phototoxicity potential of commercial glyphosate-containing formulations.

    Science.gov (United States)

    de Ávila, Renato Ivan; Teixeira, Gabriel Campos; Veloso, Danillo Fabrini Maciel Costa; Moreira, Larissa Cleres; Lima, Eliana Martins; Valadares, Marize Campos

    2017-12-01

    This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm 2 ) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Development of Testing Methodologies to Evaluate Postflight Locomotor Performance

    Science.gov (United States)

    Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Bloomberg, J. J.

    2006-01-01

    Crewmembers experience locomotor and postural instabilities during ambulation on Earth following their return from space flight. Gait training programs designed to facilitate recovery of locomotor function following a transition to a gravitational environment need to be accompanied by relevant assessment methodologies to evaluate their efficacy. The goal of this paper is to demonstrate the operational validity of two tests of locomotor function that were used to evaluate performance after long duration space flight missions on the International Space Station (ISS).

  3. Assessing potential impacts associated with contamination events in water distribution systems : a sensitivity analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M. J.; Janke, R.; Taxon, T. N. (Decision and Information Sciences); ( EVS); (EPA)

    2010-11-01

    An understanding of the nature of the adverse effects that could be associated with contamination events in water distribution systems is necessary for carrying out vulnerability analyses and designing contamination warning systems. This study examines the adverse effects of contamination events using models for 12 actual water systems that serve populations ranging from about 104 to over 106 persons. The measure of adverse effects that we use is the number of people who are exposed to a contaminant above some dose level due to ingestion of contaminated tap water. For this study the number of such people defines the impact associated with an event. We consider a wide range of dose levels in order to accommodate a wide range of potential contaminants. For a particular contaminant, dose level can be related to a health effects level. For example, a dose level could correspond to the median lethal dose, i.e., the dose that would be fatal to 50% of the exposed population. Highly toxic contaminants may be associated with a particular response at a very low dose level, whereas contaminants with low toxicity may only be associated with the same response at a much higher dose level. This report focuses on the sensitivity of impacts to five factors that either define the nature of a contamination event or involve assumptions that are used in assessing exposure to the contaminant: (1) duration of contaminant injection, (2) time of contaminant injection, (3) quantity or mass of contaminant injected, (4) population distribution in the water distribution system, and (5) the ingestion pattern of the potentially exposed population. For each of these factors, the sensitivities of impacts to injection location and contaminant toxicity are also examined. For all the factors considered, sensitivity tends to increase with dose level (i.e., decreasing toxicity) of the contaminant, with considerable inter-network variability. With the exception of the population distribution (factor 4

  4. Sensitivity of reproductive potential to environmental factors in sheep and goats

    International Nuclear Information System (INIS)

    Chemineau, P.; Terqui, M.

    1986-01-01

    Ovulation rate, embryo survival, postnatal mortality, interval from parturition to conception, age at first parturition, number of parturitions before culling, and age at culling collectively declineate the ability of a breed to cope with the local environment and management which are often harsh and suboptimal. In tropical and subtropical countries, the reproductive performance of goat and sheep is low and far from their maximum potential. Identification of the main limiting factors and determination of the breed's sensitivity to these factors are essential preliminary steps before choosing the method(s) to improve reproductive performance in such countries. (author)

  5. Effects of pinealectomy on the neuroendocrine reproductive system and locomotor activity in male European sea bass, Dicentrarchus labrax.

    Science.gov (United States)

    Cowan, Mairi; Paullada-Salmerón, José A; López-Olmeda, José Fernando; Sánchez-Vázquez, Francisco Javier; Muñoz-Cueto, José A

    2017-05-01

    The seasonally changing photoperiod controls the timing of reproduction in most fish species, however, the transduction of this photoperiodic information to the reproductive axis is still unclear. This study explored the potential role of two candidate neuropeptide systems, gonadotropin-inhibitory hormone (Gnih) and kisspeptin, as mediators between the pineal organ (a principle transducer of photoperiodic information) and reproductive axis in male European sea bass, Dicentrarchus labrax. Two seven-day experiments of pinealectomy (Px) were performed, in March (end of reproductive season) and August (resting season). Effects of Px and season on the brain expression of gnih (sbgnih) and its receptor (sbgnihr), kisspeptins (kiss1, kiss2) and their receptors (kissr2, kissr3) and gonadotropin-releasing hormone (gnrh1, gnrh2, gnrh3) and the main brain receptor (gnrhr-II-2b) genes, plasma melatonin levels and locomotor activity rhythms were examined. Results showed that Px reduced night-time plasma melatonin levels. Gene expression analyses demonstrated a sensitivity of the Gnih system to Px in March, with a reduction in sbgnih in the mid-hindbrain, a region with bilateral connections to the pineal organ. In August, kiss2 levels increased in Px animals but not in controls. Significant differences in expression were observed for diencephalic sbgnih, sbgnihr, kissr3 and tegmental gnrh2 between seasons. Recordings of locomotor activity following surgery revealed a change from light-synchronised to free-running rhythmic behavior. Altogether, the Gnih and Kiss2 sensitivity to Px and seasonal differences observed for Gnih and its receptor, Gnrh2, and the receptor for Kiss2 (Kissr3), suggested they could be mediators involved in the relay between environment and seasonal reproduction. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Neuropharmacology of light-induced locomotor activation.

    Science.gov (United States)

    Amato, Davide; Pum, Martin E; Groos, Dominik; Lauber, Andrea C; Huston, Joseph P; Carey, Robert J; de Souza Silva, Maria A; Müller, Christian P

    2015-08-01

    Presentation of non-aversive light stimuli for several seconds was found to reliably induce locomotor activation and exploratory-like activity. Light-induced locomotor activity (LIA) can be considered a convenient simple model to study sensory-motor activation. LIA was previously shown to coincide with serotonergic and dopaminergic activation in specific cortical areas in freely moving and anesthetized animals. In the present study we explore the neuropharmacology of LIA using a receptor antagonist/agonist approach in rats. The non-selective 5-HT2-receptor antagonist ritanserin (1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. Selective antagonism of either the 5-HT2A-receptor by MDL 11,939 (0.1-0.4 mg/kg, i.p.), or the 5-HT2C-receptor by SDZ SER 082 (0.125-0.5 mg/kg, i.p.), alone or in combination, had no significant influence on LIA. Also the selective 5-HT1A-receptor antagonist, WAY 100635 (0.4 mg/kg, i.p.) did not affect LIA. Neither did the preferential dopamine D2-receptor antagonist, haloperidol (0.025-0.1 mg/kg, i.p.) nor the D2/D3-receptor agonist, quinpirole (0.025-0.5 mg/kg, i.p.) affect the expression of LIA. However, blocking the glutamatergic NMDA-receptor with phencyclidine (PCP, 1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. This effect was also observed with ketamine (10 mg/kg, i.p.). These findings suggest that serotonin and dopamine receptors abundantly expressed in the cortex do not mediate light-stimulus triggered locomotor activity. PCP and ketamine effects, however, suggest an important role of NMDA receptors in LIA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Serotonin‐induced bistability of turtle motoneurones caused by a nifedipine‐sensitive calcium plateau potential

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1989-01-01

    1. The effect of serotonin on the firing properties of motoneurones was studied in transverse sections of the adult turtle spinal cord in vitro with intracellular recording techniques. 2. In normal medium, turtle motoneurones adapt from an initial high frequency to a low steady firing during...... of the frequency jump was shortened as the amplitude of the activation pulse was increased. From a positive holding potential the after‐depolarization exceeded spike threshold and its duration increased with an increase in steady bias current. The effect of serotonin on turtle motoneurones could be blocked....... It is concluded that serotonin induces a Ca2+‐dependent and nifedipine‐sensitive plateau potential in turtle motoneurones primarily by reducing a K+‐current responsible for the slow after‐hyperpolarization....

  8. The precision of locomotor odometry in humans.

    Science.gov (United States)

    Durgin, Frank H; Akagi, Mikio; Gallistel, Charles R; Haiken, Woody

    2009-03-01

    Two experiments measured the human ability to reproduce locomotor distances of 4.6-100 m without visual feedback and compared distance production with time production. Subjects were not permitted to count steps. It was found that the precision of human odometry follows Weber's law that variability is proportional to distance. The coefficients of variation for distance production were much lower than those measured for time production for similar durations. Gait parameters recorded during the task (average step length and step frequency) were found to be even less variable suggesting that step integration could be the basis for non-visual human odometry.

  9. Cocaine-induced locomotor activity in rats selectively bred for low and high voluntary running behavior.

    Science.gov (United States)

    Brown, Jacob D; Green, Caroline L; Arthur, Ian M; Booth, Frank W; Miller, Dennis K

    2015-02-01

    The rewarding effects of physical activity and abused drugs are caused by stimulation of similar brain pathways. Low (LVR) and high (HVR) voluntary running lines were developed by selectively breeding Wistar rats on running distance performance on postnatal days 28-34. We hypothesized that LVR rats would be more sensitive to the locomotor-activating effects of cocaine than HVR rats due to their lower motivation for wheel running. We investigated how selection for LVR or HVR behavior affects inherited activity responses: (a) open field activity levels, (b) habituation to an open field environment, and (c) the locomotor response to cocaine. Open field activity was measured for 80 min on three successive days (days 1-3). Data from the first 20 min were analyzed to determine novelty-induced locomotor activity (day 1) and the habituation to the environment (days 1-3). On day 3, rats were acclimated to the chamber for 20 min and then received saline or cocaine (10, 20, or 30 mg/kg) injection. Dopamine transporter (DAT) protein in the nucleus accumbens was measured via Western blot. Selecting for low and high voluntary running behavior co-selects for differences in inherent (HVR > LVR) and cocaine-induced (LVR > HVR) locomotor activity levels. The differences in the selected behavioral measures do not appear to correlate with DAT protein levels. LVR and HVR rats are an intriguing physical activity model for studying the interactions between genes related to the motivation to run, to use drugs of abuse, and to exhibit locomotor activity.

  10. Potential of roselle and blue pea in the dye-sensitized solar cell

    Science.gov (United States)

    Dayang, S.; Irwanto, M.; Gomesh, N.; Ismail, B.

    2017-09-01

    This paper discovers the use of natural dyes from Roselle flower and Blue Pea flower which act as a sensitizer in DSSC and in addition has a potential in absorbing visible light spectrum. The dyes were extracted using distilled water (DI) and ethanol (E) extract solvent in an ultrasonic cleaner for 30 minutes with a frequency of 37 Hz by using `degas' mode at the temperature of 30°C. Absorption spectra of roselle dye and blue pea dye with different extract solvent were tested using Evolution 201 UV-Vis Spectrophotometer. It was found that Roselle dye absorbs at a range of 400 nm - 620 nm and Blue Pea absorbs at the range of wavelength 500 nm - 680 nm. Fourier-Transform Infrared (FTIR) was used to identify the functional active group in extract dye. The concept of Dye-Sensitized Solar Cell (DSSC) similar to photosynthesis process has attracted much attention since it demonstrates a great potential due to the use of low-cost materials and environmentally friendly sources of technology.

  11. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

    Science.gov (United States)

    Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

    2017-09-01

    S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

  12. The evolution of locomotor rhythmicity in tetrapods.

    Science.gov (United States)

    Ross, Callum F; Blob, Richard W; Carrier, David R; Daley, Monica A; Deban, Stephen M; Demes, Brigitte; Gripper, Janaya L; Iriarte-Diaz, Jose; Kilbourne, Brandon M; Landberg, Tobias; Polk, John D; Schilling, Nadja; Vanhooydonck, Bieke

    2013-04-01

    Differences in rhythmicity (relative variance in cycle period) among mammal, fish, and lizard feeding systems have been hypothesized to be associated with differences in their sensorimotor control systems. We tested this hypothesis by examining whether the locomotion of tachymetabolic tetrapods (birds and mammals) is more rhythmic than that of bradymetabolic tetrapods (lizards, alligators, turtles, salamanders). Species averages of intraindividual coefficients of variation in cycle period were compared while controlling for gait and substrate. Variance in locomotor cycle periods is significantly lower in tachymetabolic than in bradymetabolic animals for datasets that include treadmill locomotion, non-treadmill locomotion, or both. When phylogenetic relationships are taken into account the pooled analyses remain significant, whereas the non-treadmill and the treadmill analyses become nonsignificant. The co-occurrence of relatively high rhythmicity in both feeding and locomotor systems of tachymetabolic tetrapods suggests that the anatomical substrate of rhythmicity is in the motor control system, not in the musculoskeletal components. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  13. Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.

    Science.gov (United States)

    Arkusz, Joanna; Stępnik, Maciej; Sobala, Wojciech; Dastych, Jarosław

    2010-11-10

    The aim of this study was to find differentially regulated genes in THP-1 monocytic cells exposed to sensitizers and nonsensitizers and to investigate if such genes could be reliable markers for an in vitro predictive method for the identification of skin sensitizing chemicals. Changes in expression of 35 genes in the THP-1 cell line following treatment with chemicals of different sensitizing potential (from nonsensitizers to extreme sensitizers) were assessed using real-time PCR. Verification of 13 candidate genes by testing a large number of chemicals (an additional 22 sensitizers and 8 nonsensitizers) revealed that prediction of contact sensitization potential was possible based on evaluation of changes in three genes: IL8, HMOX1 and PAIMP1. In total, changes in expression of these genes allowed correct detection of sensitization potential of 21 out of 27 (78%) test sensitizers. The gene expression levels inside potency groups varied and did not allow estimation of sensitization potency of test chemicals. Results of this study indicate that evaluation of changes in expression of proposed biomarkers in THP-1 cells could be a valuable model for preliminary screening of chemicals to discriminate an appreciable majority of sensitizers from nonsensitizers. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Second and third generation voltage-sensitive fluorescent proteins for monitoring membrane potential

    Directory of Open Access Journals (Sweden)

    Amelie Perron

    2009-06-01

    Full Text Available Over the last decade, optical neuroimaging methods have been enriched by engineered biosensors derived from fluorescent protein (FP reporters fused to protein detectors that convert physiological signals into changes of intrinsic FP fluorescence. These FP-based indicators are genetically encoded, and hence targetable to specific cell populations within networks of heterologous cell types. Among this class of biosensors, the development of optical probes for membrane potential is both highly desirable and challenging. A suitable FP voltage sensor would indeed be a valuable tool for monitoring the activity of thousands of individual neurons simultaneously in a non-invasive manner. Previous prototypic genetically-encoded FP voltage indicators achieved a proof of principle but also highlighted several difficulties such as poor cell surface targeting and slow kinetics. Recently, we developed a new series of FRET-based Voltage-Sensitive Fluorescent Proteins (VSFPs, referred to as VSFP2s, with efficient targeting to the plasma membrane and high responsiveness to membrane potential signaling in excitable cells. In addition to these FRET-based voltage sensors, we also generated a third series of probes consisting of single FPs with response kinetics suitable for the optical imaging of fast neuronal signals. These newly available genetically-encoded reporters for membrane potential will be instrumental for future experimental approaches directed toward the understanding of neuronal network dynamics and information processing in the brain. Here, we review the development and current status of these novel fluorescent probes.

  15. Pore helix domain is critical to camphor sensitivity of transient receptor potential vanilloid 1 channel.

    Science.gov (United States)

    Marsakova, Lenka; Touska, Filip; Krusek, Jan; Vlachova, Viktorie

    2012-04-01

    The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1. The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5-bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C. The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5-bisphosphate on the inner leaflet of the plasma membrane. The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo.

  16. Sensitivity analysis and parameter estimation for distributed hydrological modeling: potential of variational methods

    Directory of Open Access Journals (Sweden)

    W. Castaings

    2009-04-01

    Full Text Available Variational methods are widely used for the analysis and control of computationally intensive spatially distributed systems. In particular, the adjoint state method enables a very efficient calculation of the derivatives of an objective function (response function to be analysed or cost function to be optimised with respect to model inputs.

    In this contribution, it is shown that the potential of variational methods for distributed catchment scale hydrology should be considered. A distributed flash flood model, coupling kinematic wave overland flow and Green Ampt infiltration, is applied to a small catchment of the Thoré basin and used as a relatively simple (synthetic observations but didactic application case.

    It is shown that forward and adjoint sensitivity analysis provide a local but extensive insight on the relation between the assigned model parameters and the simulated hydrological response. Spatially distributed parameter sensitivities can be obtained for a very modest calculation effort (~6 times the computing time of a single model run and the singular value decomposition (SVD of the Jacobian matrix provides an interesting perspective for the analysis of the rainfall-runoff relation.

    For the estimation of model parameters, adjoint-based derivatives were found exceedingly efficient in driving a bound-constrained quasi-Newton algorithm. The reference parameter set is retrieved independently from the optimization initial condition when the very common dimension reduction strategy (i.e. scalar multipliers is adopted.

    Furthermore, the sensitivity analysis results suggest that most of the variability in this high-dimensional parameter space can be captured with a few orthogonal directions. A parametrization based on the SVD leading singular vectors was found very promising but should be combined with another regularization strategy in order to prevent overfitting.

  17. A novel pH sensitive water soluble fluorescent nanomicellar sensor for potential biomedical applications.

    Science.gov (United States)

    Georgiev, Nikolai I; Bryaskova, Rayna; Tzoneva, Rumiana; Ugrinova, Iva; Detrembleur, Christophe; Miloshev, Stoyan; Asiri, Abdullah M; Qusti, Abdullah H; Bojinov, Vladimir B

    2013-11-01

    Herein we report on the synthesis and sensor activity of a novel pH sensitive probe designed as highly water-soluble fluorescent micelles by grafting of 1,8-naphthalimide-rhodamine bichromophoric FRET system (RNI) to the PMMA block of a well-defined amphiphilic diblock copolymer-poly(methyl methacrylate)-b-poly(methacrylic acid) (PMMA48-b-PMAA27). The RNI-PMMA48-b-PMAA27 adduct is capable of self-assembling into micelles with a hydrophobic PMMA core, containing the anchored fluorescent probe, and a hydrophilic shell composed of PMAA block. Novel fluorescent micelles are able to serve as a highly sensitive pH probe in water and to internalize successfully HeLa and HEK cells. Furthermore, they showed cell specificity and significantly higher photostability than that of a pure organic dye label such as BODIPY. The valuable properties of the newly prepared fluorescent micelles indicate the high potential of the probe for future biological and biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Assessment of Irritation and Sensitization Potential of Eight Baby Skin Care Products.

    Science.gov (United States)

    Galzote, Carlos; Thomas, Mini; Sachdev, Mukta

    2016-10-01

    Ethnic differences in skin sensitivity suggest that greater emphasis be focused on understanding a product's effect in diverse populations. The irritation and/or sensitization potential of 8 baby skin care products in Indian adults were evaluated using cumulative irritation tests (CIT) and human repeat insult patch testing (HRIPT) protocols. Healthy males or females aged 18 to 65 years of Indian ethnicity were treated with each of 6 products (cream, hair oil, lotion, body wash, shampoo, and baby soap) using CIT (n = 25) and HRIPT (n = 200). Baby powder and baby oil were evaluated by CIT (n = 25) and HRIPT (n = 107) in separate studies. CITs were conducted over 14 days; HRIPTs were conducted over 10 weeks. In both CIT and HRIPT, most products were considered mild, with no irritation. Baby soap and powder elicited reactions in the HRIPT induction phase, with positive challenge phase reactions (3 subjects), but were affirmed to be nonallergenic in the rechallenge phase. In these studies, 8 baby skin care products were evaluated by both CIT and HRIPT in Indian adults. The results of the studies indicated that all of the tested products were nonallergenic and nonirritating. J Drugs Dermatol. 2016;15(10):1244-1248.

  19. The potential role of postsynaptic phospholipase C activity in synaptic facilitation and behavioral sensitization in Aplysia.

    Science.gov (United States)

    Fulton, Daniel; Condro, Michael C; Pearce, Kaycey; Glanzman, David L

    2008-07-01

    Previous findings indicate that synaptic facilitation, a cellular mechanism underlying sensitization of the siphon withdrawal response (SWR) in Aplysia, depends on a cascade of postsynaptic events, including activation of inositol triphosphate (IP3) receptors and release of Ca2+ from postsynaptic intracellular stores. These findings suggest that phospholipase C (PLC), the enzyme that catalyzes IP3 formation, may play an important role in postsynaptic signaling during facilitation and learning in Aplysia. Using the PLC inhibitor U73122, we found that PLC activity is required for synaptic facilitation following a 10-min treatment with 5-HT, as measured at 20 min after 5-HT washout. Prior work has indicated that facilitation at this time is supported primarily by postsynaptic processes. To determine whether postsynaptic PLC activity is involved in 5-HT-mediated facilitatory actions, we examined the effect of U73122 on enhancement of the response of motor neurons isolated in cell culture to glutamate, the sensory neuron transmitter. A 10-min application of 5-HT induced persistent (>40 min) enhancement of glutamate-evoked potentials (Glu-EPs) recorded from isolated motor neurons, and this enhancement was blocked by U73122. Finally, we showed that injecting U73122 into intact animals before behavioral training impaired intermediate-term sensitization, indicating that PLC activity contributes to this form of nonassociative learning.

  20. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  1. Sensitivity to structure in action sequences: An infant event-related potential study.

    Science.gov (United States)

    Monroy, Claire D; Gerson, Sarah A; Domínguez-Martínez, Estefanía; Kaduk, Katharina; Hunnius, Sabine; Reid, Vincent

    2017-05-06

    Infants are sensitive to structure and patterns within continuous streams of sensory input. This sensitivity relies on statistical learning, the ability to detect predictable regularities in spatial and temporal sequences. Recent evidence has shown that infants can detect statistical regularities in action sequences they observe, but little is known about the neural process that give rise to this ability. In the current experiment, we combined electroencephalography (EEG) with eye-tracking to identify electrophysiological markers that indicate whether 8-11-month-old infants detect violations to learned regularities in action sequences, and to relate these markers to behavioral measures of anticipation during learning. In a learning phase, infants observed an actor performing a sequence featuring two deterministic pairs embedded within an otherwise random sequence. Thus, the first action of each pair was predictive of what would occur next. One of the pairs caused an action-effect, whereas the second did not. In a subsequent test phase, infants observed another sequence that included deviant pairs, violating the previously observed action pairs. Event-related potential (ERP) responses were analyzed and compared between the deviant and the original action pairs. Findings reveal that infants demonstrated a greater Negative central (Nc) ERP response to the deviant actions for the pair that caused the action-effect, which was consistent with their visual anticipations during the learning phase. Findings are discussed in terms of the neural and behavioral processes underlying perception and learning of structured action sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.

    Science.gov (United States)

    Liang, M; Lee, M C; O'Neill, J; Dickenson, A H; Iannetti, G D

    2016-08-01

    Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. Copyright © 2016 the American Physiological Society.

  3. Functional reorganization of the locomotor network in Parkinson patients with freezing of gait.

    Directory of Open Access Journals (Sweden)

    Brett W Fling

    Full Text Available Freezing of gait (FoG is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson's disease (PD and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA and the following locomotor hubs: 1 subthalamic nucleus (STN, 2 mesencephalic and 3 cerebellar locomotor region (MLR and CLR, respectively within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG- and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i clinical, ii self-reported and iii objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG- patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a

  4. PROBLEMAS LOCOMOTORES EM FRANGOS DE CORTE - REVISÃO. / LOCOMOTOR PROBLEMS IN BROILER CHICKENS - A REVIEW.

    Directory of Open Access Journals (Sweden)

    IBIARA CORREIA DE LIMA ALMEIDA PAZ

    2008-12-01

    Full Text Available O bem estar animal é, sem dúvida, um dos pontos em que os produtores de aves devem se atentar para conseguir melhor rentabilidade e colocação no mercado externo. No entanto, é necessário ter uma ampla idéia de que alguns pontos impostos por mercados importadores, muitas vezes não tem fundamento científico e tratam-se mais de barreiras não tarifárias que de problemas de produção propriamente ditos. Dentre os vários fatores que afetam o bem estar animal pode-se destacar a incidência de problemas locomotores, principalmente em animais confinados. Estes distúrbios podem acarretar em perdas de até 6% em lotes comercias de frangos de corte, além de outras perdas não mensuráveis em linhas de abate, por fraturas e hematomas. Existem diversas metodologias para diagnosticar problemas locomotores, entretanto, a mais difundida na indústria avícola é o Gait Score, por sua facilidade de aplicação e por englobar os diferentes tipos de problemas locomotores. Sabe-se, contudo que esta metodologia é bastante subjetiva e pode inferir  em  diferentes  níveis  de  avaliação  dependendo  do método  utilizado. Os  problemas locomotores devem ser prevenidos já que depois de estabelecidos as perdas são inevitáveis.

  5. Locomotor sequence learning in visually guided walking

    DEFF Research Database (Denmark)

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo

    2016-01-01

    walking. In addition, we determined how age (i.e., healthy young adults vs. children) and biomechanical factors (i.e., walking speed) affected the rate and magnitude of locomotor sequence learning. The results showed that healthy young adults (age 24 ± 5 years, N = 20) could learn a specific sequence...... of step lengths over 300 training steps. Younger children (age 6-10 years, N = 8) have lower baseline performance, but their magnitude and rate of sequence learning was the same compared to older children (11-16 years, N = 10) and healthy adults. In addition, learning capacity may be more limited...... to modify step length from one trial to the next. Our sequence learning paradigm is derived from the serial reaction-time (SRT) task that has been used in upper limb studies. Both random and ordered sequences of step lengths were used to measure sequence-specific and sequence non-specific learning during...

  6. Integrated Locomotor Function Tests for Countermeasure Evaluation

    Science.gov (United States)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

    2005-01-01

    Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the

  7. Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants.

    Science.gov (United States)

    Gross, Joshua D; Kaski, Shane W; Schroer, Adam B; Wix, Kimberley A; Siderovski, David P; Setola, Vincent

    2018-02-01

    Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of administration (sensitization and conditioned place preference) were unaffected, suggesting that RGS12 does not function in support of the rewarding properties of these psychostimulants. To test whether observed response changes upon RGS12 loss were caused by changes to dopamine transporter expression and/or function, we prepared crude membranes from the brains of wild-type and RGS12-null mice and measured dopamine transporter-selective [ 3 H]WIN 35428 binding, revealing an increase in dopamine transporter levels in the ventral-but not dorsal-striatum of RGS12-null mice. To address dopamine transporter function, we prepared striatal synaptosomes and measured [ 3 H]dopamine uptake. Consistent with increased [ 3 H]WIN 35428 binding, dopamine transporter-specific [ 3 H]dopamine uptake in RGS12-null ventral striatal synaptosomes was found to be increased. Decreased amphetamine-induced locomotor activity and increased [ 3 H]WIN 35428 binding were recapitulated with an independent RGS12-null mouse strain. Thus, we propose that RGS12 regulates dopamine transporter expression and function in the ventral striatum, affecting amphetamine- and cocaine-induced increases in dopamine levels that specifically elicit acute hyperlocomotor responses.

  8. Effect of thermal acclimation on locomotor energetics and locomotor performance in a lungless salamander, Desmognathus ochrophaeus.

    Science.gov (United States)

    Feder, M E

    1986-03-01

    To determine the effects of thermal acclimation upon locomotor performance and the rate of oxygen consumption (MO2) during activity, small (less than 3 g), lungless salamanders, Desmognathus ochrophaeus Cope, were acclimated to three temperatures (5, 13 and 21 degrees C) and exercised at various controlled speeds within an exercise wheel while their MO2 was measured. MO2 increased with speed at low speeds (less than 14 cm min-1). Although animals could sustain greater speeds, MO2 did not increase further. These small, exclusively skin-breathing salamanders could increase their MO2 9-11 times during exercise and could sustain nearly half of the oxygen flux expected across a similar surface area of the mammalian lung. However, their maximum aerobic speed was remarkably slow (14 cm min-1) and their net cost of transport remarkably large (15-17 ml O2 g-1 km-1). Thermal acclimation affected MO2 during activity, the maximum sustainable speed and locomotor stamina in different ways. During exercise at 13 degrees C, cold-acclimated animals had a significantly greater MO2 than warm-acclimated animals, but did not differ in stamina or the maximum sustainable speed. During exercise at 21 degrees C, cold acclimation did not affect the MO2 significantly, but it decreased the stamina and increased the rate of lactate accumulation. Thus, these results suggest that thermal acclimation of the MO2 is not tightly coupled to thermal acclimation of locomotor performance in salamanders.

  9. Potential natural sensitizers extracted from the skin of Canarium odontophyllum fruits for dye-sensitized solar cells

    Science.gov (United States)

    Lim, Andery; Kumara, N. T. R. N.; Tan, Ai Ling; Mirza, Aminul Huq; Chandrakanthi, R. L. N.; Petra, Mohammad Iskandar; Ming, Lim Chee; Senadeera, G. K. R.; Ekanayake, Piyasiri

    2015-03-01

    Possibility of use of dye extract from skin samples of a seasonal, indigenous fruit from Borneo, namely Canarium odontophyllum, in dye sensitized solar cells (DSSCs) are explored. Three main groups of flavonoid pigments are detected and these pigments exhibit different UV-vis absorption properties, and hence showing different light harvesting capabilities. When applied in DSSCs. The detected pigment constituents of the extract consist of aurone (maritimein), anthocyanidin (pelargonidin) and anthocyanidin (cyanidin derivatives). When tested in DSSC, the highest conversion efficiency of 1.43% is exhibited by cyanidin derivatives, and this is followed by conversion efficiencies of 0.51% and 0.79% for aurone and pelargonidin, respectively. It is shown that individual pigments, like cyanidin derivatives and pelargonidin, exhibit higher power conversion efficiency when compared to that of C.odontophyllum skin pigment mixture (with a conversion efficiency of only 0.68%). The results indicate a possibility of masking effects of the pigments when used as a mixture. The acidification of C.odontophyllum skin pigments with concentrated hydrochloric acid improves the conversion efficiency of the mixture from 0.68% to 0.99%. The discussion in this paper will draw data and observations from the variation in absorption and adsorption properties, the HOMO-LUMO levels, the energy band gaps and the functional group compositions of the detected flavonoids.

  10. Locomotor Activity and Body Temperature Patterns over a Temperature Gradient in the Highveld Mole-Rat (Cryptomys hottentotus pretoriae).

    Science.gov (United States)

    Haupt, Meghan; Bennett, Nigel C; Oosthuizen, Maria K

    2017-01-01

    African mole-rats are strictly subterranean mammals that live in extensive burrow systems. High humidity levels in the burrows prevent mole-rats from thermoregulating using evaporative cooling. However, the relatively stable environment of the burrows promotes moderate temperatures and small daily temperature fluctuations. Mole-rats therefore display a relatively wide range of thermoregulation abilities. Some species cannot maintain their body temperatures at a constant level, whereas others employ behavioural thermoregulation. Here we test the effect of ambient temperature on locomotor activity and body temperature, and the relationship between the two parameters, in the highveld mole-rat. We exposed mole-rats to a 12L:12D and a DD light cycle at ambient temperatures of 30°C, 25°C and 20°C while locomotor activity and body temperature were measured simultaneously. In addition, we investigated the endogenous rhythms of locomotor activity and body temperature at different ambient temperatures. Mole-rats displayed nocturnal activity at all three ambient temperatures and were most active at 20°C, but least active at 30°C. Body temperature was highest at 30°C and lowest at 20°C, and the daily cycle was highly correlated with locomotor activity. We show that the mole-rats have endogenous rhythms for both locomotor activity and body temperature. However, the endogenous body temperature rhythm appears to be less robust compared to the locomotor activity rhythm. Female mole-rats appear to be more sensitive to temperature changes than males, increased heterothermy is evident at lower ambient temperatures, whilst males show smaller variation in their body temperatures with changing ambient temperatures. Mole-rats may rely more heavily on behavioural thermoregulation as it is more energy efficient in an already challenging environment.

  11. An 'Early Warning System' for the prevention of dredging potential impacts on sensitive areas

    Science.gov (United States)

    Piermattei, Viviana; Martellucci, Riccardo; Pierattini, Alberto; Bonamano, Simone; Paladini de Mendoza, Francesco; Albani, Marta; Stefanì, Chiara; Madonia, Alice; Fersini, Giorgio; Marcelli, Marco

    2016-04-01

    Coastal marine ecosystems are increasingly subject to multiple pressures and stressors produced by the effects of human activities. Intense and frequent disturbances which affect marine environment can derive from dredging activity, which is a fundamental management for most ports and harbours. The potential environmental effects of dredging procedures are generally due to the excavation of material from the sea bottom and the relocation elsewhere for disposal, overflow from the dredger and loss of material from pipelines during transport. Depending on the location and the intensity of these activities the marine environment, particularly sensitive areas, may be affected by dredging. The main environmental effects can be associated with suspended sediments and increases in turbidity into the water column, which can have adverse effects on marine animals and plants by reducing light penetration and by physical disturbance. For this reason it is fundamental to implement a real time monitoring system to control and prevent negative effects, enabling a rapid response to adverse water quality conditions and a fast activation of mitigation procedures, in agreement with all the reference authorities. In this work we present the development of an innovative 'Early Warning System' based on fixed stations, ad hoc in situ surveys and forecasting models, which was applied to a dredging activity carried out in the Gulf of Gaeta (Latium, Italy). It represents an extension of the C-CEMS (Civitavecchia Coastal Environmental Monitoring System) network, which is operative in the Tyrrhenian sea since 2005.

  12. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  13. Assessing the sensitivity of information distortion to four potential influences in studies of risky choice

    Directory of Open Access Journals (Sweden)

    Seth A. Miller

    2013-11-01

    Full Text Available The emergence of a leading alternative during the course of a decision is known to bias the evaluation of new information in a manner that favors that alternative. We report 3 studies that address the sensitivity of predecisional information distortion and its effects in hypothetical risky decisions with regard to 4 potential influences: choice domain, repeated choice, memory requirements, and intermediate progress questions. In Experiment 1 (N = 515, the magnitude of information distortion was similar in 5 choice domains (varied between participants involving monetary gambles, song downloads, frequent-flyer miles, political decisions, or medical decisions. Information distortion mediated the relationship between our manipulation of initial preferences and participants' final choices, with the magnitude of the indirect effect being roughly similar across domains. These results replicate and extend previous findings. Additionally, distortion decreased significantly over 4 similar decision problems (within participants, but remained significant in the fourth problem. In Experiment 2 (N = 214, information distortion increased significantly when previously viewed information remained available, apparently because reiterating that information strengthened emerging preferences. In Experiment 3 (N = 223, the removal of intermediate progress questions that measure information distortion and emerging preferences did not significantly affect final choices, again replicating previous results. We conclude that predecisional information distortion is a relatively stable and robust phenomenon that deserves a prominent role in descriptive theories of choice.

  14. The potential sensitivity of tropical plants to increased ultraviolet-B radiation

    International Nuclear Information System (INIS)

    Ziska, L.H.

    1996-01-01

    Little is known concerning the impact of stratospheric ozone depletion and increasing ultraviolet (UV)-B radiation on the phenology and growth of tropical plants. This is because, ostensibly, tropical plants are already exposed to relatively high levels of UV-B radiation (relative to a temperate environment) and should, therefore, possess a greater degree of tolerance to increased UV-B radiation. In this brief review I hope to show that, potentially, direct and indirect effects on photosynthesis, assimilate partitioning, phenology and biomass could occur in both tropical crops (e.g. cassava, rice) and native species (e.g. Cecropia obtusifolia (Bertol. Fl)., Tetramolopium humile (Gray), Nana sandwicensis L.). However, it should be noted that differences in sensitivity to UV-B radiation can be related to experimental conditions, and care should be taken to ensure that the quantity and quality of background solar radiation remains at near ambient conditions. Nevertheless, by integrating current and past studies on the impact of UV-B radiation on tropical species, I hope to be able to demonstrate that photosynthesis, morphology and growth in tropical plants could be directly affected by UV-B radiation and that UV-B radiation may be a factor in species and community dynamics in natural plant populations in the tropics

  15. Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

    International Nuclear Information System (INIS)

    Mosaddeghi, M.

    1989-01-01

    The function of α 1 -adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with [ 3 H]inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 μM potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC 50 was decreased from 3.93 ± 0.42 to 1.91 ± 0.31 μM NE. Concentrations of 0.1-100 μM and 0.1-10 μM cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 μM NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 μM prazosin. Cocaine (10 μM) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 μM prazosin. [ 3 H]Prazosin saturation and NE [ 3 H]prazosin competition binding studies using crude membrane preparations showed that 10 μM cocaine did not alter binding parameters B max , K d , Hill slope, and IC 50 . Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis

  16. Dose and time relationships of the radioprotector WR-2721 on locomotor activity in mice

    International Nuclear Information System (INIS)

    Landauer, M.R.; Davis, H.D.; Dominitz, J.A.; Weiss, J.F.

    1987-01-01

    The effects of the radioprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) on locomotor activity were evaluated in CD2F1 male mice. Separate groups of animals (N = 10/group) received an IP injection of vehicle, 25, 50, 100, 200, or 400 mg/kg of WR-2721 immediately before testing. Horizontal and vertical activity were measured using a Digiscan automated animal activity monitor. The latency to onset and duration of action of each dose of the radioprotector were recorded. For both behavioral measures, a significant reduction was observed in activity at doses of 200 and 400 mg/kg. A dose of 200 mg/kg had a 12- to 14-min latency to onset and significantly reduced behavioral activity for 3 hr. Mice injected with 400 mg/kg exhibited locomotor deficits within 8-10 min and were affected for up to 9 hr. The ED50 for horizontal and vertical activities at 1 hr postinjection were determined to be 271 and 105 mg/kg, respectively. The results demonstrate that significant reductions in locomotor activity are exhibited at doses of 200 mg/kg or more and that vertical activity was more sensitive to the disruptive effects of WR-2721 than was horizontal activity

  17. Evidence for a role of orexin/hypocretin system in vestibular lesion-induced locomotor abnormalities in rats

    Directory of Open Access Journals (Sweden)

    Leilei Pan

    2016-07-01

    Full Text Available Vestibular damage can induce locomotor abnormalities in both animals and humans. Rodents with bilateral vestibular loss showed vestibular deficits syndrome such as circling, opisthotonus as well as locomotor and exploratory hyperactivity. Previous studies have investigated the changes in the dopamine system after vestibular loss, but the results are inconsistent and inconclusive. Numerous evidences indicate that the orexin system is implicated in central motor control. We hypothesized that orexin may be potentially involved in vestibular loss-induced motor disorders. In this study, we examined the effects of arsanilate- or 3, 3′-iminodipropionitrile (IDPN-induced vestibular lesion (AVL or IVL on the orexin-A (OXA labeling in rat hypothalamus using immunohistochemistry. The vestibular lesion-induced locomotor abnormalities were recorded and verified using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.. The effects of the orexin receptor type 1 antagonist SB334867 (16 μg, i.c.v. on these behavior responses were also investigated. At 72 h post-AVL and IVL, animals exhibited vestibular deficit syndrome and locomotor hyperactivity in the home cages. These responses were significantly alleviated by JNJ7777120 which also eliminated AVL-induced increases in exploratory behavior in an open field. The numbers of OXA-labeled neurons in the hypothalamus were significantly increased in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48 and 72 h post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory behavior in the AVL animals. These results suggested that the alteration of OXA expression might contribute to locomotor abnormalities after acute vestibular lesion. The orexin receptors might be the potential therapeutic targets for vestibular disorders.

  18. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Potential Sensitivity of Québec's Breeding Birds to Climate Change

    Directory of Open Access Journals (Sweden)

    Jean-Luc DesGranges

    2010-12-01

    Full Text Available We examined the relationship between climatic factors and the distribution of breeding birds in southern Québec, Canada to identify the species whose distribution renders them potentially sensitive to climate change in the study area. We determined the degree of association between the distribution of 65 breeding bird species (601 presence-absence squares of the Atlas of the Breeding Birds of Québec and climate variables (212 climatological stations in operation for at least 20 years over the period 1953-1984 by statistically correcting for the effects of several factors that are correlated with bird distribution. Factors considered were the nature and scale of land cover patterns that included vegetation types and landscape characterization, geographical coordinates, and elevation. Canonical Correspondence Analysis (CCA was used to investigate the effect of climatic variables on breeding bird distribution. Independent variables accounted for a total of 29.1% of the variation in the species matrix. A very large portion of the variance explained by climate variables was shared with spatial variables, reflecting the relationships among latitude, longitude, elevation, and climate. After correcting for the effect of land cover variables, climatic variables still explained 11.4% of the variation in the species matrix, with temperature, i.e., warmer summers and milder winters, having a greater influence than precipitation, i.e., wetter summers. Of the 65 species, 14 appeared to be particularly climate-sensitive. Eight are insectivorous neotropical migrants and six species are at the northern limit of their range in the study area. The opposite is largely true for the eight others; they are practically absent from the southern part of the study area, except for the Dark-eyed Junco (Junco hyemalis, which is widespread there. The White-breasted Nuthatch (Sitta carolinensis is the only resident species that seemed responsive to climatic variables, i

  20. Reliability review of the remote tool delivery system locomotor

    Energy Technology Data Exchange (ETDEWEB)

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  1. Locomotor differences in Mongolian gerbils with the effects of ...

    African Journals Online (AJOL)

    Locomotor differences in Mongolian gerbils with the effects of midazolam ... African Health Sciences ... We subjected the gerbils to an adapted “Open Field” to determine the possible effects on central nervous system of midazolam. Gerbils ...

  2. Hesperidin effects on behavior and locomotor activity of diabetic ...

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    2016-11-09

    Nov 9, 2016 ... Author(s) agree that this article remains permanently open access under the terms of the Creative ... diabetes in animals and patients with type1 (Northam et ... measured were, locomotor activities, standing position, the time of.

  3. Differences in the locomotor-activating effects of indirect serotonin agonists in habituated and non-habituated rats.

    Science.gov (United States)

    Halberstadt, Adam L; Buell, Mahálah R; Price, Diana L; Geyer, Mark A

    2012-07-01

    The indirect serotonin (5-HT) agonist 3,4-methylenedioxymethamphetamine (MDMA) produces a distinct behavioral profile in rats consisting of locomotor hyperactivity, thigmotaxis, and decreased exploration. The indirect 5-HT agonist α-ethyltryptamine (AET) produces a similar behavioral profile. Using the Behavioral Pattern Monitor (BPM), the present investigation examined whether the effects of MDMA and AET are dependent on the novelty of the testing environment. These experiments were conducted in Sprague-Dawley rats housed on a reversed light cycle and tested during the dark phase of the light/dark cycle. We found that racemic MDMA (RS-MDMA; 3 mg/kg, SC) increased locomotor activity in rats tested in novel BPM chambers, but had no effect on locomotor activity in rats habituated to the BPM chambers immediately prior to testing. Likewise, AET (5 mg/kg, SC) increased locomotor activity in non-habituated animals but not in animals habituated to the test chambers. These results were unexpected because previous reports indicate that MDMA has robust locomotor-activating effects in habituated animals. To further examine the influence of habituation on MDMA-induced locomotor activity, we conducted parametric studies with S-(+)-MDMA (the more active enantiomer) in habituated and non-habituated rats housed on a standard or reversed light cycle. Light cycle was included as a variable due to reported differences in sensitivity to serotonergic ligands during the dark and light phases. In confirmation of our initial studies, rats tested during the dark phase and habituated to the BPM did not show an S-(+)-MDMA (3 mg/kg, SC)-induced increase in locomotor activity, whereas non-habituated rats did. By contrast, in rats tested during the light phase, S-(+)-MDMA increased locomotor activity in both non-habituated and habituated rats, although the response in habituated animals was attenuated. The finding that habituation and light cycle interact to influence MDMA- and AET

  4. On understanding the relationship between structure in the potential surface and observables in classical dynamics: A functional sensitivity analysis approach

    International Nuclear Information System (INIS)

    Judson, R.S.; Rabitz, H.

    1987-01-01

    The relationship between structure in the potential surface and classical mechanical observables is examined by means of functional sensitivity analysis. Functional sensitivities provide maps of the potential surface, highlighting those regions that play the greatest role in determining the behavior of observables. A set of differential equations for the sensitivities of the trajectory components are derived. These are then solved using a Green's function method. It is found that the sensitivities become singular at the trajectory turning points with the singularities going as eta -3 /sup // 2 , with eta being the distance from the nearest turning point. The sensitivities are zero outside of the energetically and dynamically allowed region of phase space. A second set of equations is derived from which the sensitivities of observables can be directly calculated. An adjoint Green's function technique is employed, providing an efficient method for numerically calculating these quantities. Sensitivity maps are presented for a simple collinear atom--diatom inelastic scattering problem and for two Henon--Heiles type Hamiltonians modeling

  5. The anatomy and physiology of the locomotor system.

    Science.gov (United States)

    Farley, Alistair; McLafferty, Ella; Hendry, Charles

    Mobilisation is one of the activities of living. The term locomotor system refers to those body tissues and organs responsible for movement. Nurses and healthcare workers should be familiar with the body structures that enable mobilisation to assist those in their care with this activity. This article outlines the structure and function of the locomotor system, including the skeleton, joints, muscles and muscle attachments. Two common bone disorders, osteoporosis and osteoarthritis, are also considered.

  6. Modular Diversification of the Locomotor System in Damselfishes (Pomacentridae)

    OpenAIRE

    Aguilar-Medrano, Rosalia; Frederich, Bruno; Barber, Paul H.

    2016-01-01

    As fish move and interact with their aquatic environment by swimming, small morphological variations of the locomotor system can have profound implications on fitness. Damselfishes (Pomacentridae) have inhabited coral reef ecosystems for more than 50 million years. As such, habitat preferences and behavior could significantly constrain the morphology and evolvability of the locomotor system. To test this hypothesis, we used phylogenetic comparative methods on morphometric, ecological and beha...

  7. Assessment of the Sensitizing Potential of Processed Peanut Proteins in Brown Norway Rats: Roasting Does Not Enhance Allergenicity

    DEFF Research Database (Denmark)

    Kroghsbo, Stine; Rigby, Neil M.; Johnson, Philip L F

    2014-01-01

    and not allergens present in their natural food matrix. Objectives The aim was to investigate if thermal processing increases sensitization potential of whole peanuts via the oral route. In parallel, the effect of heating on sensitization potential of the major peanut allergen Ara h 1 was assessed via...... the intraperitoneal route. Methods Sensitization potential of processed peanut products and Ara h 1 was examined in Brown Norway (BN) rats by oral administration of blanched or oil-roasted peanuts or peanut butter or by intraperitoneal immunization of purified native (N-), heated (H-) or heat glycated (G-)Ara h 1....... Levels of specific IgG and IgE were determined by ELISA and IgE functionality was examined by rat basophilic leukemia (RBL) cell assay. Results In rats dosed orally, roasted peanuts induced significant higher levels of specific IgE to NAra h 1 and 2 than blanched peanuts or peanut butter...

  8. The Use of Germinants to Potentiate the Sensitivity of Bacillus anthracis Spores to Peracetic Acid.

    Science.gov (United States)

    Celebi, Ozgur; Buyuk, Fatih; Pottage, Tom; Crook, Ant; Hawkey, Suzanna; Cooper, Callum; Bennett, Allan; Sahin, Mitat; Baillie, Leslie

    2016-01-01

    Elimination of Bacillus anthracis spores from the environment is a difficult and costly process due in part to the toxicity of current sporicidal agents. For this reason we investigated the ability of the spore germinants L-alanine (100 mM) and inosine (5 mM) to reduce the concentration of peracetic acid (PAA) required to inactivate B. anthracis spores. While L-alanine significantly enhanced (p = 0.0085) the bactericidal activity of 500 ppm PAA the same was not true for inosine suggesting some form of negative interaction. In contrast the germinant combination proved most effective at 100 ppm PAA (p = 0.0009). To determine if we could achieve similar results in soil we treated soil collected from the burial site of an anthrax infected animal which had been supplemented with spores of the Sterne strain of B. anthracis to increase the level of contamination to 10(4) spores/g. Treatment with germinants followed 1 h later by 5000 ppm PAA eliminated all of the spores. In contrast direct treatment of the animal burial site using this approach delivered using a back pack sprayer had no detectable effect on the level of B. anthracis contamination or on total culturable bacterial numbers over the course of the experiment. It did trigger a significant, but temporary, reduction (p < 0.0001) in the total spore count suggesting that germination had been triggered under real world conditions. In conclusion, we have shown that the application of germinants increase the sensitivity of bacterial spores to PAA. While the results of the single field trial were inconclusive, the study highlighted the potential of this approach and the challenges faced when attempting to perform real world studies on B. anthracis spores contaminated sites.

  9. The use of germinants to potentiate the sensitivity of Bacillus anthracis spores to peracetic acid

    Directory of Open Access Journals (Sweden)

    Ozgur eCelebi

    2016-01-01

    Full Text Available Elimination of Bacillus anthracis spores from the environment is a difficult and costly process due in part to the toxicity of current sporicidal agents. For this reason we investigated the ability of the spore germinants L-alanine (100 mM and inosine (5 mM to reduce the concentration of peracetic acid (PAA required to inactivate B.anthracis spores. While L-alanine significantly enhanced (p=0.0085 the bactericidal activity of 500 ppm PAA the same was not true for inosine suggesting some form of negative interaction. In contrast the germinant combination proved most effective at 100 ppm PAA (p=0.0009. To determine if we could achieve similar results in soil we treated soil collected from the burial site of an anthrax infected animal which had been supplemented with spores of the Sterne strain of B.anthracis to increase the level of contamination to 104 spores/g. Treatment with germinants followed one hour later by 5000 ppm PAA eliminated all of the spores. In contrast direct treatment of the animal burial site using this approach delivered using a back pack sprayer had no detectable effect on the level of B.anthracis contamination or on total culturable bacterial numbers over the course of the experiment. It did trigger a significant, but temporary, reduction (p<0.0001 in the total spore count suggesting that germination had been triggered under real world conditions. In conclusion, we have shown that the application of germinants increase the sensitivity of bacterial spores to PAA. While the results of the single field trial were inconclusive, the study highlighted the potential of this approach and the challenges faced when attempting to perform real world studies on B.anthracis spores contaminated sites.

  10. A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

    Science.gov (United States)

    Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

  11. Dermal Sensitization Potential of DIGL-RP Solid Propellant in Guinea Pigs

    Science.gov (United States)

    1989-10-01

    y ’,c. ADM$$S (ft, SWOt , &Wd ZIP Cod 7b. ADDRESS (City, State, arid ZIP Code) Letterman Army Institute of Research Fort Detrick Presidio of San...for contact sensitization. Toxicol Appl Pharmacol 1969; Suppl 3:90-102. 7. Buehler EV, Griffith JF. Experimental skin sensitization in the guinea pig

  12. Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

    NARCIS (Netherlands)

    Hettinga, JVE; Lemstra, W; Meijer, C; Dam, WA; Uges, DRA; Konings, AWT; DeVries, EGE; Kampinga, HH

    1997-01-01

    In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 43 degrees C during cDDP exposure was found to increase drug

  13. Computer models versus reality: how well do in silico models currently predict the sensitization potential of a substance.

    Science.gov (United States)

    Teubner, Wera; Mehling, Anette; Schuster, Paul Xaver; Guth, Katharina; Worth, Andrew; Burton, Julien; van Ravenzwaay, Bennard; Landsiedel, Robert

    2013-12-01

    National legislations for the assessment of the skin sensitization potential of chemicals are increasingly based on the globally harmonized system (GHS). In this study, experimental data on 55 non-sensitizing and 45 sensitizing chemicals were evaluated according to GHS criteria and used to test the performance of computer (in silico) models for the prediction of skin sensitization. Statistic models (Vega, Case Ultra, TOPKAT), mechanistic models (Toxtree, OECD (Q)SAR toolbox, DEREK) or a hybrid model (TIMES-SS) were evaluated. Between three and nine of the substances evaluated were found in the individual training sets of various models. Mechanism based models performed better than statistical models and gave better predictivities depending on the stringency of the domain definition. Best performance was achieved by TIMES-SS, with a perfect prediction, whereby only 16% of the substances were within its reliability domain. Some models offer modules for potency; however predictions did not correlate well with the GHS sensitization subcategory derived from the experimental data. In conclusion, although mechanistic models can be used to a certain degree under well-defined conditions, at the present, the in silico models are not sufficiently accurate for broad application to predict skin sensitization potentials. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. FDS Modeling of the Sensitivity of the Smoke Potential Values used in Fire Safety Strategies

    DEFF Research Database (Denmark)

    Corches, Andrei-Mircea; Ulriksen, Lene; Jomaas, Grunde

    2014-01-01

    To investigate the sensitivity of Fire Dynamics Simulator (FDS) with respect to the input parameters that are used to define the optical properties of the smoke, a parametric study was performed for relevant fire scenarios in an open plan office building. The parametric study mainly focuses on th...... to defining the design fires will reduce the sensitivity of the numerical fire simulation and further reduce the risk of overestimating the evacuation safety level (ESL) of the building....

  15. THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers

    International Nuclear Information System (INIS)

    Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda; Tendeloo, Viggo van; Cauwenberge, Paul van; Nelissen, Inge; Heuvel, Rosette van den; Schoeters, Greet

    2009-01-01

    Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

  16. An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

    Science.gov (United States)

    Dugan, Elizabeth A; Sagen, Jacqueline

    2015-05-01

    Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain.

  17. Assessment of the sensitizing potential of processed peanut proteins in Brown Norway rats: roasting does not enhance allergenicity.

    Directory of Open Access Journals (Sweden)

    Stine Kroghsbo

    Full Text Available BACKGROUND: IgE-binding of process-modified foods or proteins is the most common method for examination of how food processing affects allergenicity of food allergens. How processing affects sensitization capacity is generally studied by administration of purified food proteins or food extracts and not allergens present in their natural food matrix. OBJECTIVES: The aim was to investigate if thermal processing increases sensitization potential of whole peanuts via the oral route. In parallel, the effect of heating on sensitization potential of the major peanut allergen Ara h 1 was assessed via the intraperitoneal route. METHODS: Sensitization potential of processed peanut products and Ara h 1 was examined in Brown Norway (BN rats by oral administration of blanched or oil-roasted peanuts or peanut butter or by intraperitoneal immunization of purified native (N-, heated (H- or heat glycated (G-Ara h 1. Levels of specific IgG and IgE were determined by ELISA and IgE functionality was examined by rat basophilic leukemia (RBL cell assay. RESULTS: In rats dosed orally, roasted peanuts induced significant higher levels of specific IgE to NAra h 1 and 2 than blanched peanuts or peanut butter but with the lowest level of RBL degranulation. However, extract from roasted peanuts was found to be a superior elicitor of RBL degranulation. Process-modified Ara h 1 had similar sensitizing capacity as NAra h 1 but specific IgE reacted more readily with process-modified Ara h 1 than with native. CONCLUSIONS: Peanut products induce functional specific IgE when dosed orally to BN rats. Roasted peanuts do not have a higher sensitizing capacity than blanched peanuts. In spite of this, extract from roasted peanuts is a superior elicitor of RBL cell degranulation irrespectively of the peanut product used for sensitization. The results also suggest that new epitopes are formed or disclosed by heating Ara h 1 without glucose.

  18. Limitations imposed by wearing armour on Medieval soldiers' locomotor performance.

    Science.gov (United States)

    Askew, Graham N; Formenti, Federico; Minetti, Alberto E

    2012-02-22

    In Medieval Europe, soldiers wore steel plate armour for protection during warfare. Armour design reflected a trade-off between protection and mobility it offered the wearer. By the fifteenth century, a typical suit of field armour weighed between 30 and 50 kg and was distributed over the entire body. How much wearing armour affected Medieval soldiers' locomotor energetics and biomechanics is unknown. We investigated the mechanics and the energetic cost of locomotion in armour, and determined the effects on physical performance. We found that the net cost of locomotion (C(met)) during armoured walking and running is much more energetically expensive than unloaded locomotion. C(met) for locomotion in armour was 2.1-2.3 times higher for walking, and 1.9 times higher for running when compared with C(met) for unloaded locomotion at the same speed. An important component of the increased energy use results from the extra force that must be generated to support the additional mass. However, the energetic cost of locomotion in armour was also much higher than equivalent trunk loading. This additional cost is mostly explained by the increased energy required to swing the limbs and impaired breathing. Our findings can predict age-associated decline in Medieval soldiers' physical performance, and have potential implications in understanding the outcomes of past European military battles.

  19. The possible interaction of dopamine system in nucleus accumbens shell and glutamate system of prelimbic region on locomotor activity in rat

    Directory of Open Access Journals (Sweden)

    Hatam Ahmadi

    2013-06-01

    Full Text Available Background: Nucleus accumbens (NAc and prefrontal cortex (PFC dopaminergic and glutamatergic systems are involved in regulating of locomotor activity behaviors. This study has investigated the interaction of NAc shell dopaminergic system and prelimbic glutamatergic systems in regulating locomotor activity and related parameters. Methods: The aim of this study was the effect the drugs injection interaction in the brain of male Wistar rats on locomotor activity and related parameters, in the order of this purpose, open field apparatus that automatically recorded locomotor activity was employed. Unilateral intra-cerebral injection of drugs was done. Results: Unilateral intra-prelimbic injection of D-AP7 (N-methyl-D-aspartic acid= NMDA receptor antagonist; 0.25, 0.5 and 1μg/μl did not alter locomotor activity behaviors. However, infusion of NMDA (0.9μg/μl in this region increased locomotor activity (P<0.01, whereas decreased rearing (P<0.01 and grooming (P<0.01 which was blocked by D-AP7 (0.25μg/μl (P<0.01. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1μg/μl into the left NAc shell did not alter locomotor activity. However, injection of SKF38393 (dopamine D1 receptor agonist; 4μg/μl into the left NAc shell increased locomotor activity (P<0.05 which was blocked by SCH23390 (0.25μg/μl (P<0.01. Furthermore, the subthreshold dose infusion of SCH23390 (0.25μg/μl into the left NAc shell reduced the effect of intra- prelimbic NMDA on locomotor activity (P<0.01. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1μg/μl potentiated the middle dose (P<0.05, whereas decreased the higher dose of intra-left prelimbic NMDA response (P<0.05 on locomotor activity. Conclusion: The results suggested a modulatory effect of the NAc shell dopaminergic system on increased locomotor activity by activating glutamate system in prelimbic.

  20. Excessive sensitivity of momentum densities to crystal potentials as a reason for difficulties in verifying positron enhancement theories

    International Nuclear Information System (INIS)

    Sormann, H.

    2001-01-01

    The excessive sensitivity of the momentum densities of electron-positron annihilation pairs (MDAP) to crystal potentials found in this study severely deteriorates a possibility to use a comparison between theoretical and experimental MDAP results as a criterion for the legitimacy of electron-positron interaction theories. Illustrative examples are given. (orig.)

  1. 20170921 - An evaluation of selected (Q)SARs/expert systems for the Prediction of Skin Sensitization Potential (ASCCT)

    Science.gov (United States)

    Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal models such as the Local Lymph Node Assay (LLNA) and the Guinea Pig Maximization Test (GPMT). In recent years, EU regulations have provided a strong incentiv...

  2. How many cervical cancer cases can potentially be prevented using a more sensitive screening test at young age?

    NARCIS (Netherlands)

    I.M.C.M. de Kok (Inge); J.M. van Rosmalen (Joost); K. Rozemeijer (Kirsten); C. Penning (Corine); M. van Ballegooijen (Marjolein)

    2014-01-01

    textabstractThe human papilloma virus (HPV) DNA test has higher sensitivity than cytology for cervical cancer screening. Therefore, cervical cancer cases that are missed by cytology could potentially be identified if we use primary HPV testing. Studies showed that HPV screening is the preferred

  3. Adaptive locomotor behavior in larval zebrafish.

    Science.gov (United States)

    Portugues, Ruben; Engert, Florian

    2011-01-01

    In this study we report that larval zebrafish display adaptive locomotor output that can be driven by unexpected visual feedback. We develop a new assay that addresses visuomotor integration in restrained larval zebrafish. The assay involves a closed-loop environment in which the visual feedback a larva receives depends on its own motor output in a way that resembles freely swimming conditions. The experimenter can control the gain of this closed feedback loop, so that following a given motor output the larva experiences more or less visual feedback depending on whether the gain is high or low. We show that increases and decreases in this gain setting result in adaptive changes in behavior that lead to a generalized decrease or increase of motor output, respectively. Our behavioral analysis shows that both the duration and tail beat frequency of individual swim bouts can be modified, as well as the frequency with which bouts are elicited. These changes can be implemented rapidly, following an exposure to a new gain of just 175 ms. In addition, modifications in some behavioral parameters accumulate over tens of seconds and effects last for at least 30 s from trial to trial. These results suggest that larvae establish an internal representation of the visual feedback expected from a given motor output and that the behavioral modifications are driven by an error signal that arises from the discrepancy between this expectation and the actual visual feedback. The assay we develop presents a unique possibility for studying visuomotor integration using imaging techniques available in the larval zebrafish.

  4. Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development

    Directory of Open Access Journals (Sweden)

    Siguang Xu

    2016-01-01

    Full Text Available The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC and acid sensitive ionic channel (ASIC. ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na+ across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

  5. Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

    International Nuclear Information System (INIS)

    Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

    2015-01-01

    In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5–20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10 −2 , 1.48×10 −2 , 4.14×10 −2 , and 6.03×10 −2 , 9.44×10 −2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose. - Highlights: • Radiation sensitivity of gallic acid and its esters were studied in intermediate and low radiation dose range using EPR. • While the irradiated samples of GA were presented complex EPR spectra the esters presented singlet ESR spectra. • Samples were compared to alanine in terms of the dosimetric point of view. • The radiation sensitivities of the investigated materials were very low at intermediate doses. • Lauryl ester of gallic acid was found to present a good sensitivity below 10 Gy

  6. KM3NeT/ARCA sensitivity and discovery potential for neutrino point-like sources

    Directory of Open Access Journals (Sweden)

    Trovato A.

    2016-01-01

    Full Text Available KM3NeT is a large research infrastructure with a network of deep-sea neutrino telescopes in the abyss of the Mediterranean Sea. Of these, the KM3NeT/ARCA detector, installed in the KM3NeT-It node of the network, is optimised for studying high-energy neutrinos of cosmic origin. Sensitivities to galactic sources such as the supernova remnant RXJ1713.7-3946 and the pulsar wind nebula Vela X are presented as well as sensitivities to a generic point source with an E−2 spectrum which represents an approximation for the spectrum of extragalactic candidate neutrino sources.

  7. Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury

    OpenAIRE

    Cummings, Brian J.; Engesser-Cesar, Christie; Anderson, Aileen J.

    2007-01-01

    Locomotor impairments after spinal cord injury (SCI) are often assessed using open-field rating scales. These tasks have the advantage of spanning the range from complete paralysis to normal walking; however, they lack sensitivity at specific levels of recovery. Additionally, most supplemental assessments were developed in rats, not mice. For example, the horizontal ladder beam has been used to measure recovery in the rat after SCI. This parametric task results in a videotaped archival record...

  8. The sensitization potential of sunscreen after ablative fractional skin resurfacing using modified human repeated insult patch test.

    Science.gov (United States)

    Boonchai, Waranya; Sathaworawong, Angkana; Wongpraparut, Chanisada; Wanitphakdeedecha, Rungsima

    2015-10-01

    Ablative fractional skin resurfacing has become popular and proven to be useful in treating scars, photoaging and wrinkles. Although post-inflammatory hyperpigmentation (PIH) is the most common complication especially in dark-skinned patients like Asian. Several modalities have been used to overcome the PIH. To determine the sensitization potential of sunscreen applied immediately after ablative fractional skin resurfacing. Sixty volunteers were recruited. Of these 30 subjects were from previous ablative fractional skin resurfacing study who applied broad-spectrum sunscreen containing anti-inflammatory agent starting on the first day after resurfacing and another 30 non-resurfacing subjects had applied the same sunscreen on the intact skin. All subjects were patch/photopatch tested for sensitization study by using modified human repeated insult patch test (HRIPT). There were significantly higher sensitization rate of UV-filter, octocrylene and the sunscreen in resurfacing group than in non-resurfacing group. Early application of sunscreen after ablative fractional skin resurfacing has increased the incidence of sensitization potential of sunscreen. The sunscreen is recommended to start using from D3 after fractional ablative skin resurfacing to ensure the complete recovery of skin barrier and minimize the risk of sensitization.

  9. An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins

    NARCIS (Netherlands)

    Knippels, L.M.J.; Houben, G.F.; Spanhaak, S.; Penninks, A.H.

    1999-01-01

    We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA

  10. The Polarization-Sensitive Bolometers for SPICA and their Potential Use for Ground-Based Application

    Science.gov (United States)

    Reveret, Vincent

    2018-01-01

    CEA is leading the development of Safari-POL, an imaging-polarimeter aboard the SPICA space observatory (ESA M5). SPICA will be able to reach unprecedented sensitivities thanks to its cooled telescope and its ultra-sensitive detectors. The detector assembly of Safari-POL holds three arrays that are cooled down to 50 mK and correspond to three spectral bands : 100, 200 and 350 microns. The detectors (silicon bolometers), benefit from the Herschel/PACS legacy and are also a big step forward in term of sensitivity (improved by two orders of magnitude compared to PACS bolometers) and for polarimetry capabilities. Indeed, each pixel is intrinsically sensitive to two polarization components (Horizontal and Vertical). We will present the Safari-POL concept, the first results of measurements made on the detectors, and future plans for possible ground-based instruments using this technology. We will also present the example of the ArTéMiS camera, installed at APEX, that was developped as a ground-based conterpart of the PACS photometer.

  11. Structural and effective connectivity reveals potential network-based influences on category-sensitive visual areas

    Directory of Open Access Journals (Sweden)

    Nicholas eFurl

    2015-05-01

    Full Text Available Visual category perception is thought to depend on brain areas that respond specifically when certain categories are viewed. These category-sensitive areas are often assumed to be modules (with some degree of processing autonomy and to act predominantly on feedforward visual input. This modular view can be complemented by a view that treats brain areas as elements within more complex networks and as influenced by network properties. This network-oriented viewpoint is emerging from studies using either diffusion tensor imaging to map structural connections or effective connectivity analyses to measure how their functional responses influence each other. This literature motivates several hypotheses that predict category-sensitive activity based on network properties. Large, long-range fiber bundles such as inferior fronto-occipital, arcuate and inferior longitudinal fasciculi are associated with behavioural recognition and could play crucial roles in conveying backward influences on visual cortex from anterior temporal and frontal areas. Such backward influences could support top-down functions such as visual search and emotion-based visual modulation. Within visual cortex itself, areas sensitive to different categories appear well-connected (e.g., face areas connect to object- and motion sensitive areas and their responses can be predicted by backward modulation. Evidence supporting these propositions remains incomplete and underscores the need for better integration of DTI and functional imaging.

  12. A Further Examination of Potential Observation Network Design with Mesoscale Ensemble Sensitivities in Complex Terrain

    Science.gov (United States)

    2013-03-01

    a successful means of determining forecast error in synoptic storms (Hakim and Torn 2008), storms undergoing extratropical transition (Torn and...677. Torn, R. D., and G. J. Hakim, 2009: Initial condition sensitivity of Western-Pacific extratropical transitions determined using ensemble-based

  13. The Potential Observation Network Design with Mesoscale Ensemble Sensitivities in Complex Terrain

    Science.gov (United States)

    2012-03-01

    in synoptic storms , extratropical transition and developing hurricanes. Because they rely on lagged covariances from a finite-sized ensemble, they...diagnose predictors of forecast error in synoptic storms , extratropical transition and developing hurricanes. Because they rely on lagged covariances...sensitivities can be used successfully to diagnose predictors of forecast error in synoptic storms (Torn and Hakim 2008), extratropical transition (Torn and

  14. Modular diversification of the locomotor system in damselfishes (Pomacentridae).

    Science.gov (United States)

    Aguilar-Medrano, Rosalía; Frédérich, Bruno; Barber, Paul H

    2016-05-01

    As fish move and interact with their aquatic environment by swimming, small morphological variations of the locomotor system can have profound implications on fitness. Damselfishes (Pomacentridae) have inhabited coral reef ecosystems for more than 50 million years. As such, habitat preferences and behavior could significantly constrain the morphology and evolvability of the locomotor system. To test this hypothesis, we used phylogenetic comparative methods on morphometric, ecological and behavioral data. While body elongation represented the primary source of variation in the locomotor system of damselfishes, results also showed a diverse suite of morphological combinations between extreme morphologies. Results show clear associations between behavior, habitat preferences, and morphology, suggesting ecological constraints on shape diversification of the locomotor system. In addition, results indicate that the three modules of the locomotor system are weakly correlated, resulting in versatile and independent characters. These results suggest that Pomacentridae is shape may result from the interaction between (1) integrated parts of morphological variation that maintain overall swimming ability and (2) relatively independent parts of the morphology that facilitate adaptation and diversification. © 2016 Wiley Periodicals, Inc.

  15. Determination of the interatomic potential from elastic differential cross sections at fixed energy: Functional sensitivity analysis approach

    International Nuclear Information System (INIS)

    Ho, T.; Rabitz, H.

    1989-01-01

    Elastic differential cross sections in atomic crossed beam experiments contain detailed information about the underlying interatomic potentials. The functional sensitivity density of the cross sections with respect to the potential δσ(θ)/δV(R) reveals such information and has been implemented in an iterative inversion procedure, analogous to that of the Newton--Raphson technique. The stability of the inversion is achieved with the use of the regularization method of Tikhonov and Miller. It is shown that given a set of well resolved and noise-free differential cross section data within a limited angular range and given a reasonable starting reference potential, the recovered potential accurately resembles the desired one in the important region, i.e., the region to which the scattering data are sensitive. The region of importance depends upon the collision energy relative to the well depth of the potential under study; usually a higher collision energy penetrates deeper into the repulsive part of the potential and thus accordingly yields a more accurate potential in that part. The inversion procedure produces also a quality function indicating the well determined radial region. Moreover, the extracted potential is quite independent of the functional form of the reference potential in contrast to curve fitting approaches. As illustrations, the model inert gas systems He--Ne and Ne--Ar have been considered. For collision energies within an order of magnitude of the associated potential well depth, the attractive part of the potential can be determined to high precision provided that scattering data at small enough angles are available

  16. Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury.

    Science.gov (United States)

    Züchner, Mark; Kondratskaya, Elena; Sylte, Camilla B; Glover, Joel C; Boulland, Jean-Luc

    2018-01-15

    were two main locomotor frequencies, but injured spinal cords exhibited a shift towards the higher frequency. Injury also altered the neurochemical dependence of locomotor CPG output, such that injured spinal cords, unlike control spinal cords, were incapable of generating low frequency rhythmic coordinated activity in the presence of NMDA and dopamine alone. Thus, the neonatal spinal cord also exhibits remarkable functional recovery after lumbar injuries, but the neurochemical sensitivity of locomotor circuitry is modified in the process. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  17. An evaluation of selected in silico models for the assessment of skin sensitization potential – performance and practical utility considerations (QSAR conference)

    Science.gov (United States)

    Skin sensitization remains an important endpoint for consumers, manufacturers and regulators. Although the development of alternative approaches to assess skin sensitization potential has been extremely active over many years, the implication of regulations such as REACH and the ...

  18. Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

    Science.gov (United States)

    Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

    2015-02-01

    In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

  19. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  20. Delineating the Diversity of Spinal Interneurons in Locomotor Circuits.

    Science.gov (United States)

    Gosgnach, Simon; Bikoff, Jay B; Dougherty, Kimberly J; El Manira, Abdeljabbar; Lanuza, Guillermo M; Zhang, Ying

    2017-11-08

    Locomotion is common to all animals and is essential for survival. Neural circuits located in the spinal cord have been shown to be necessary and sufficient for the generation and control of the basic locomotor rhythm by activating muscles on either side of the body in a specific sequence. Activity in these neural circuits determines the speed, gait pattern, and direction of movement, so the specific locomotor pattern generated relies on the diversity of the neurons within spinal locomotor circuits. Here, we review findings demonstrating that developmental genetics can be used to identify populations of neurons that comprise these circuits and focus on recent work indicating that many of these populations can be further subdivided into distinct subtypes, with each likely to play complementary functions during locomotion. Finally, we discuss data describing the manner in which these populations interact with each other to produce efficient, task-dependent locomotion. Copyright © 2017 the authors 0270-6474/17/3710835-07$15.00/0.

  1. Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

    Science.gov (United States)

    Benthall, Katelyn N.; Hough, Ryan A.

    2016-01-01

    Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the

  2. Conditioned Place Preference to Acetone Inhalation and the Effects on Locomotor Behavior and 18FDG Uptake

    Energy Technology Data Exchange (ETDEWEB)

    Pai, J.C.; Dewey, S.L.; Schiffer, W.; Lee, D.

    2006-01-01

    Acetone is a component in many inhalants that have been widely abused. While other solvents have addictive potential, such as toluene, it is unclear whether acetone alone contains addictive properties. The locomotor, relative glucose metabolism and abusive effects of acetone inhalation were studied in animals using the conditioned place preference (CPP) paradigm and [18F]2-fluorodeoxy-D-glucose (18FDG) imaging. The CPP apparatus contains two distinct conditioning chambers and a middle adaptation chamber, each lined with photocells to monitor locomotor activity. Adolescent Sprague-Dawley rats (n=16; 90-110 g) were paired with acetone in least preferred conditioning chamber, determined on the pretest day. The animals were exposed to a 10,000 ppm dose for an hour, alternating days with air. A CPP test was conducted after the 3rd, 6th and 12th pairing. In these same animals, the relative glucose metabolism effects were determined using positron emission tomography (PET) imaging with 18FDG. Following the 3rd pairing, there was a significant aversion to the acetone paired chamber (190.9 ± 13.7 sec and 241.7 ± 16.9 sec, acetone and air, respectively). After the 6th pairing, there was no significant preference observed with equal time spent in each chamber (222 ± 21 sec and 207 ± 20 sec, acetone and air-paired, respectively). A similar trend was observed after the 12th pairing (213 ± 21 sec and 221 ± 22 sec, acetone and air-paired, respectively). Locomotor analysis indicated a significant decrease (p<0.05) from air pairings to acetone pairings on the first and sixth pairings. The observed locomotor activity was characteristic of central nervous system (CNS) depressants, without showing clear abusive effects in this CPP model. In these studies, acetone vapors were not as reinforcing as other solvents, shown by overall lack of preference for the acetone paired side of the chamber. PET imaging indicated a regionally specific distribution of 18FDG uptake following

  3. Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

    Science.gov (United States)

    Benthall, Katelyn N; Hough, Ryan A; McClellan, Andrew D

    2017-01-01

    Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3-5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results

  4. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves.

    Science.gov (United States)

    Wienecke, Jacob; Enríquez Denton, Manuel; Stecina, Katinka; Kirkwood, Peter A; Hultborn, Hans

    2015-01-01

    In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves). Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2) and spontaneously occurring locomotor drive potentials (LDPs) in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves), with a slow rate (periods 9-104 s, mean 39 ± 17 SD). Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated.

  5. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves

    Directory of Open Access Journals (Sweden)

    Katinka eStecina

    2015-02-01

    Full Text Available In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves. Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2 and spontaneously occurring locomotor drive potentials (LDPs in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves, with a slow rate (periods 9 - 104 s, mean 39 ± 17 SD. Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated.

  6. Locomotor adaptability in persons with unilateral transtibial amputation.

    Science.gov (United States)

    Darter, Benjamin J; Bastian, Amy J; Wolf, Erik J; Husson, Elizabeth M; Labrecque, Bethany A; Hendershot, Brad D

    2017-01-01

    Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb.

  7. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo

    2013-01-01

    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  8. Anatomía del Aparato Locomotor, 2010-11

    OpenAIRE

    Juanes Méndez, Juan Antonio

    2010-01-01

    I. Materiales de clase: 1.Sistema Oseo. Las Articulaciones: definición, clasificaciones; 2.Esqueleto Axial; 3.Esqueleto Apendicular; 4. Organización del sistema nervioso periférico. Inervación del Aparato Locomotor; 5. Sistema muscular. II. Bibliografía y atlas Establecer la correlación morfofuncional del aparato locomotor necesaria para la deducción deficitaria derivada de las alteraciones de la dinámica osteoarticular. Esta asignatura se imparte en el primer curso del Grado en Terapia Oc...

  9. The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia.

    Science.gov (United States)

    Ding, Zhaofeng; Li, Jinrong; Spiegel, Daniel P; Chen, Zidong; Chan, Lily; Luo, Guangwei; Yuan, Junpeng; Deng, Daming; Yu, Minbin; Thompson, Benjamin

    2016-01-14

    Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia.

  10. Sensitivity of potential evaporation estimates to 100 years of climate variability

    NARCIS (Netherlands)

    Bartholomeus, R.P.; Stagge, J.H.; Tallaksen, L.M.; Witte, J.P.M.

    2015-01-01

    Hydrological modeling frameworks require an accurate representation of evaporation fluxes for appropriate quantification of, e.g., the water balance, soil moisture budget, recharge and groundwater processes. Many frameworks have used the concept of potential evaporation, often estimated for

  11. Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

    Science.gov (United States)

    Strada, Susanna; Unger, Nadine

    2016-04-01

    A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP) and isoprene emission. The impacts of different pollution aerosol sources (anthropogenic, biomass burning, and non-biomass burning) are investigated by performing sensitivity experiments. The model framework includes all known light and meteorological responses of photosynthesis, but uses fixed canopy structures and phenology. On a global scale, our results show that global land carbon fluxes (GPP and isoprene emission) are not sensitive to pollution aerosols, even under a global decline in surface solar radiation (direct + diffuse) by ˜ 9 %. At a regional scale, GPP and isoprene emission show a robust but opposite sensitivity to pollution aerosols in regions where forested canopies dominate. In eastern North America and Eurasia, anthropogenic pollution aerosols (mainly from non-biomass burning sources) enhance GPP by +5-8 % on an annual average. In the northwestern Amazon Basin and central Africa, biomass burning aerosols increase GPP by +2-5 % on an annual average, with a peak in the northwestern Amazon Basin during the dry-fire season (+5-8 %). The prevailing mechanism varies across regions: light scattering dominates in eastern North America, while a reduction in direct radiation dominates in Europe and China. Aerosol-induced GPP productivity increases in the Amazon and central Africa include an additional positive feedback from reduced canopy temperatures in response to increases in canopy conductance. In Eurasia and northeastern China, anthropogenic pollution aerosols drive a decrease in isoprene emission of -2 to -12 % on an annual average. Future research needs to incorporate the indirect effects of aerosols and possible feedbacks from dynamic carbon allocation and phenology.

  12. Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

    Directory of Open Access Journals (Sweden)

    S. Strada

    2016-04-01

    Full Text Available A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP and isoprene emission. The impacts of different pollution aerosol sources (anthropogenic, biomass burning, and non-biomass burning are investigated by performing sensitivity experiments. The model framework includes all known light and meteorological responses of photosynthesis, but uses fixed canopy structures and phenology. On a global scale, our results show that global land carbon fluxes (GPP and isoprene emission are not sensitive to pollution aerosols, even under a global decline in surface solar radiation (direct + diffuse by  ∼ 9 %. At a regional scale, GPP and isoprene emission show a robust but opposite sensitivity to pollution aerosols in regions where forested canopies dominate. In eastern North America and Eurasia, anthropogenic pollution aerosols (mainly from non-biomass burning sources enhance GPP by +5–8 % on an annual average. In the northwestern Amazon Basin and central Africa, biomass burning aerosols increase GPP by +2–5 % on an annual average, with a peak in the northwestern Amazon Basin during the dry-fire season (+5–8 %. The prevailing mechanism varies across regions: light scattering dominates in eastern North America, while a reduction in direct radiation dominates in Europe and China. Aerosol-induced GPP productivity increases in the Amazon and central Africa include an additional positive feedback from reduced canopy temperatures in response to increases in canopy conductance. In Eurasia and northeastern China, anthropogenic pollution aerosols drive a decrease in isoprene emission of −2 to −12 % on an annual average. Future research needs to incorporate the indirect effects of aerosols and possible feedbacks from dynamic carbon allocation and phenology.

  13. Bibliographic review on the potential of microorganisms, microbial products and enzymes to induce respiratory sensitization

    DEFF Research Database (Denmark)

    Martel, Cyril; Nielsen, Gunnar D.; Mari, Adriano

    respiratory sensitization when used as food and feed additives was investigated in this report. A short review of the state-of-the-art methods to predict allergenicity was also conducted. Our results indicate that there is currently no established model to predict the allergenicity of a molecule. Although in......-silico models can be useful to predict cross-reactivity between allergens, they do not take into account phenomenons like the context of presentation of the antigen to the immune system. There is no realiable, predictive in-vitro or in-vivo model of allergenicity. Cases of occupational allergy to both fungi...

  14. Response of climate to regional emissions of ozone precursors: sensitivities and warming potentials

    International Nuclear Information System (INIS)

    Berntsen, T.K.; Fuglestvedt, J.S.; Joshi, M.M.; Shine, K.P.; Hauglustaine, D.A.; Li, L.

    2005-01-01

    The response of climate to ozone perturbations caused by regional emissions of NO x or CO has been studied through a sequence of model simulations. Changes C and OH concentrations due to emission perturbations in Europe and southeast Asia have been calculated with two global 3-D chemical tracer models(CTMs; LMDzINCA and Oslo-CTM2). The radiative transfer codes of three general circulation models (GCMs; ECHAM4, UREAD and LMD) have been used to calculate the radiative forcing of the O 3 perturbations, and for a subset of the cases full GCM simulations have been performed with ECHAM4 and UREAD. The results have been aggregated to a global number in two ways: first, through integrating the global-mean radiative forcing of a sustained step change in emissions, and second through a modified concept (SGWP*) which includes possible differences in the climate sensitivity of O 3 , CH 4 and CO 2 changes. In terms of change in global tropospheric O 3 burden the two CTMs differ by less than 30%. Both CTMs show a higher north/south gradient in the sensitivity to changes in NO x emission than for CO. We are not able to conclude whether real O 3 perturbations in general have a different climate sensitivity from CO 2 . However, in both GCMs high-latitude emission perturbations lead to climate perturbations with higher (10-30%) climate sensitivities. The calculated SGWP*, for a 100 yr time horizon, are negative for three of the four CTM/GCM combinations for European emissions (-9.6 to +6.9), while for the Asian emissions the SGWP* (H=100) is always positive (+2.9 to +25) indicating a warming. For CO the SGWP* values (3.8 and 4.4 for European and Asian emissions respectively, with only the Oslo-CTM2/ECHAM4 model combination) are less regionally dependent. Our results support the view that for NO x , regionally different weighting factors for the emissions are necessary. For CO the results are more robust and one global number may be acceptable

  15. Sensitivity of soil phosphorus tests in predicting the potential risk of phosphorus loss from pasture soil

    OpenAIRE

    H. SOINNE; K. SAARIJÄRVI; M. KARPPINEN

    2008-01-01

    The objective of this study was to examine the effects of urine and dung additions on the phosphorus (P) chemistry of pasture land and to compare the sensitivity of two soil extraction methods in assessing the P-loading risk. In a field experiment, urine and dung were added to soil in amounts corresponding to single excrement portions and the soil samples, taken at certain intervals, were analysed for pHH2O, acid ammonium acetate extractable P (PAc) and water extractable total P (TPw), and mo...

  16. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

    Directory of Open Access Journals (Sweden)

    Kee Hang Lee

    Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  17. The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia

    OpenAIRE

    Ding, Zhaofeng; Li, Jinrong; Spiegel, Daniel P.; Chen, Zidong; Chan, Lily; Luo, Guangwei; Yuan, Junpeng; Deng, Daming; Yu, Minbin; Thompson, Benjamin

    2016-01-01

    Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated...

  18. Studying the physics potential of long-baseline experiments in terms of new sensitivity parameters

    International Nuclear Information System (INIS)

    Singh, Mandip

    2016-01-01

    We investigate physics opportunities to constraint the leptonic CP-violation phase δ_C_P through numerical analysis of working neutrino oscillation probability parameters, in the context of long-baseline experiments. Numerical analysis of two parameters, the “transition probability δ_C_P phase sensitivity parameter (A"M)” and the “CP-violation probability δ_C_P phase sensitivity parameter (A"C"P),” as functions of beam energy and/or baseline have been carried out. It is an elegant technique to broadly analyze different experiments to constrain the δ_C_P phase and also to investigate the mass hierarchy in the leptonic sector. Positive and negative values of the parameter A"C"P, corresponding to either hierarchy in the specific beam energy ranges, could be a very promising way to explore the mass hierarchy and δ_C_P phase. The keys to more robust bounds on the δ_C_P phase are improvements of the involved detection techniques to explore lower energies and relatively long baseline regions with better experimental accuracy.

  19. Sensitivity of soil phosphorus tests in predicting the potential risk of phosphorus loss from pasture soil

    Directory of Open Access Journals (Sweden)

    H. SOINNE

    2008-12-01

    Full Text Available The objective of this study was to examine the effects of urine and dung additions on the phosphorus (P chemistry of pasture land and to compare the sensitivity of two soil extraction methods in assessing the P-loading risk. In a field experiment, urine and dung were added to soil in amounts corresponding to single excrement portions and the soil samples, taken at certain intervals, were analysed for pHH2O, acid ammonium acetate extractable P (PAc and water extractable total P (TPw, and molybdate reactive P (MRPw. Urine additions immediately increased soil pH and MRPw, but no such response was observed in PAc extraction due to the low pH (4.65 of the extractant enhancing the resorption of P. The PAc responded to the dunginduced increase in soil total P similarly as did Pw, which suggests that both tests can serve to detect areas of high P concentration. However, water extraction was a more sensitive method for estimating short-term changes in P solubility. In pasture soils, the risk of P loss increases as a result of the interaction of urination and high P concentration in the topsoil resulting from continuous dung excretion.;

  20. Diversity in UV sensitivity and recovery potential among bacterioneuston and bacterioplankton isolates.

    Science.gov (United States)

    Santos, A L; Lopes, S; Baptista, I; Henriques, I; Gomes, N C M; Almeida, A; Correia, A; Cunha, A

    2011-04-01

    To assess the variability in UV-B (280-320 nm) sensitivity of selected bacterial isolates from the surface microlayer and underlying water of the Ria de Aveiro (Portugal) estuary and their ability to recover from previous UV-induced stress. Bacterial suspensions were exposed to UV-B radiation (3·3 W m⁻²). Effects on culturability and activity were assessed from colony counts and (3) H-leucine incorporation rates, respectively. Among the tested isolates, wide variability in UV-B-induced inhibition of culturability (37·4-99·3%) and activity (36·0-98·0%) was observed. Incubation of UV-B-irradiated suspensions under reactivating regimes (UV-A, 3·65 W m⁻²; photosynthetic active radiation, 40 W m⁻²; dark) also revealed diversity in the extent of recovery from UV-B stress. Trends of enhanced resistance of culturability (up to 15·0%) and enhanced recovery in activity (up to 52·0%) were observed in bacterioneuston isolates. Bacterioneuston isolates were less sensitive and recovered more rapidly from UV-B stress than bacterioplankton isolates, showing enhanced reduction in their metabolism during the irradiation period and decreased culturability during the recovery process compared to bacterioplankton. UV exposure can affect the diversity and activity of microbial communities by selecting UV-resistant strains and alter their metabolic activity towards protective strategies. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

  1. Perceptual-motor regulation in locomotor pointing while approaching a curb.

    Science.gov (United States)

    Andel, Steven van; Cole, Michael H; Pepping, Gert-Jan

    2018-02-01

    Locomotor pointing is a task that has been the focus of research in the context of sport (e.g. long jumping and cricket) as well as normal walking. Collectively, these studies have produced a broad understanding of locomotor pointing, but generalizability has been limited to laboratory type tasks and/or tasks with high spatial demands. The current study aimed to generalize previous findings in locomotor pointing to the common daily task of approaching and stepping on to a curb. Sixteen people completed 33 repetitions of a task that required them to walk up to and step onto a curb. Information about their foot placement was collected using a combination of measures derived from a pressure-sensitive walkway and video data. Variables related to perceptual-motor regulation were analyzed on an inter-trial, intra-step and inter-step level. Similar to previous studies, analysis of the foot placements showed that, variability in foot placement decreased as the participants drew closer to the curb. Regulation seemed to be initiated earlier in this study compared to previous studies, as shown by a decreasing variability in foot placement as early as eight steps before reaching the curb. Furthermore, it was shown that when walking up to the curb, most people regulated their walk in a way so as to achieve minimal variability in the foot placement on top of the curb, rather than a placement in front of the curb. Combined, these results showed a strong perceptual-motor coupling in the task of approaching and stepping up a curb, rendering this task a suitable test for perceptual-motor regulation in walking. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

    OpenAIRE

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2016-01-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxyt...

  3. Sensitivity of commercial pumpkin yield to potential decline among different groups of pollinating bees

    Science.gov (United States)

    Eckerter, Philipp W.; Schirmel, Jens; Cresswell, James E.; Entling, Martin H.

    2017-01-01

    The yield of animal-pollinated crops is threatened by bee declines, but its precise sensitivity is poorly known. We therefore determined the yield dependence of Hokkaido pumpkin in Germany on insect pollination by quantifying: (i) the relationship between pollen receipt and fruit set and (ii) the cumulative pollen deposition of each pollinator group. We found that approximately 2500 pollen grains per flower were needed to maximize fruit set. At the measured rates of flower visitation, we estimated that bumblebees (21 visits/flower lifetime, 864 grains/visit) or honeybees (123 visits, 260 grains) could individually achieve maximum crop yield, whereas halictid bees are ineffective (11 visits, 16 grains). The pollinator fauna was capable of delivering 20 times the necessary amount of pollen. We therefore estimate that pumpkin yield was not pollination-limited in our study region and that it is currently fairly resilient to single declines of honeybees or wild bumblebees. PMID:28573019

  4. Sensitivity of commercial pumpkin yield to potential decline among different groups of pollinating bees.

    Science.gov (United States)

    Pfister, Sonja C; Eckerter, Philipp W; Schirmel, Jens; Cresswell, James E; Entling, Martin H

    2017-05-01

    The yield of animal-pollinated crops is threatened by bee declines, but its precise sensitivity is poorly known. We therefore determined the yield dependence of Hokkaido pumpkin in Germany on insect pollination by quantifying: (i) the relationship between pollen receipt and fruit set and (ii) the cumulative pollen deposition of each pollinator group. We found that approximately 2500 pollen grains per flower were needed to maximize fruit set. At the measured rates of flower visitation, we estimated that bumblebees (21 visits/flower lifetime, 864 grains/visit) or honeybees (123 visits, 260 grains) could individually achieve maximum crop yield, whereas halictid bees are ineffective (11 visits, 16 grains). The pollinator fauna was capable of delivering 20 times the necessary amount of pollen. We therefore estimate that pumpkin yield was not pollination-limited in our study region and that it is currently fairly resilient to single declines of honeybees or wild bumblebees.

  5. Evaluation of potential meteorological triggers of large landslides in sensitive glaciomarine clay, eastern Canada

    Directory of Open Access Journals (Sweden)

    D. Gauthier

    2012-11-01

    Full Text Available Heavy rains spread over some interval preceding large landslides in sensitive glaciomarine clay in eastern Canada are often noted as a triggering or causative factor in case studies or research reports for individual landslides, although the quantity or duration of the triggering rain event has never been characterized adequately. We selected five large landslide events that occurred in the glaciomarine clay in eastern Canada, and calculated cumulative antecedent precipitation for intervals ranging between one and 365 days preceding each event. We also calculated the antecedent precipitation values for every other day in the record, and computed the relative rank of the landslide day within the complete record. Our results show that several intervals for each landslide event are highly ranked – including those preceding a presumably earthquake-triggered landslide – but overall the rankings were highly variable, ranging between 99% and 6%. The set of highest-ranking intervals are unique for each event, including both short and long-term cumulative precipitation. All of the landslides occurred in the spring months, and the release of sequestered surface and ground water during the spring ground thaw may be related to the timing of the large landslides, so that the evolution of ground frost in the early winter may be of interest for landslide prediction. We found no simple precipitation threshold for triggering large landslides in sensitive glaciomarine clay in eastern Canada, suggesting that some complex temporal and spatial combination of pre-conditions, external energy (e.g. earthquakes, precipitation triggers and other factors such as ground frost formation and thaw are required to trigger a landslide.

  6. A Global Assessment of Runoff Sensitivity to Changes in Precipitation, Potential Evaporation, and Other Factors

    NARCIS (Netherlands)

    Berghuijs, W.R.; Larsen, Joshua R.; van Emmerik, T.H.M.; Woods, Ross A.

    2017-01-01

    Precipitation (P) and potential evaporation (Ep) are commonly studied drivers of changing freshwater availability, as aridity (Ep/P) explains ∼90% of the spatial differences in mean runoff across the globe. However, it is unclear if changes in aridity over time are also the

  7. Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

    International Nuclear Information System (INIS)

    King, G.L.; Landauer, M.R.

    1990-01-01

    The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways

  8. Olanzapine affects locomotor activity and meal size in male rats

    NARCIS (Netherlands)

    van der Zwaal, Esther M.; Luijendijk, Mieneke C. M.; Evers, Simon S.; la Fleur, Susanne E.; Adan, Roger A. H.

    2010-01-01

    Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect To investigate how olanzapine affects different aspects of energy balance we used male rats to determine effects on meal patterns food preference locomotor activity and

  9. Olanzapine affects locomotor activity and meal size in male rats

    NARCIS (Netherlands)

    van der Zwaal, Esther M.; Luijendijk, Mieneke C. M.; Evers, Simon S.; la Fleur, Susanne E.; Adan, Roger A. H.

    2010-01-01

    Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect. To investigate how olanzapine affects different aspects of energy balance, we used male rats to determine effects on meal patterns, food preference, locomotor activity

  10. Inbreeding affects locomotor activity in Drosophila melanogaster at different ages

    DEFF Research Database (Denmark)

    Manenti, Tommaso; Pertoldi, Cino; Nasiri Moghadam, Neda

    2015-01-01

    The ability to move is essential for many behavioural traits closely related to fitness. Here we studied the effect of inbreeding on locomotor activity (LA) of Drosophila melanogaster at different ages under both dark and light regimes. We expected to find a decreased LA in inbred lines compared...

  11. Locomotor Sub-functions for Control of Assistive Wearable Robots

    Directory of Open Access Journals (Sweden)

    Maziar A. Sharbafi

    2017-09-01

    Full Text Available A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance: redirecting the center of mass by exerting forces on the ground. Swing: cycling the legs between ground contacts. Balance: maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies.

  12. Locomotor Sub-functions for Control of Assistive Wearable Robots.

    Science.gov (United States)

    Sharbafi, Maziar A; Seyfarth, Andre; Zhao, Guoping

    2017-01-01

    A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance : redirecting the center of mass by exerting forces on the ground. Swing : cycling the legs between ground contacts. Balance : maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies.

  13. Efffects of vigabatrin on spontaneous locomotor activity of rats

    NARCIS (Netherlands)

    Bouwman, B.M.; Rijn, C.M. van; Willems-van Bree, P.C.M.; Coenen, A.M.L.

    2003-01-01

    Effects of vigibatrin (saline, 125, 250, or 500 mg/kg i.p.) on spontaneous locomotor activity in Wistar rats were investigated. There was a dose dependent decrease in amount of locomotion for doses up to 250 mg/kg. This decrease was measurable 2-4 hours after injection and still became more

  14. Development and functional organization of spinal locomotor circuits

    DEFF Research Database (Denmark)

    Kiehn, Ole

    2011-01-01

    The coordination and timing of muscle activities during rhythmic movements, like walking and swimming, are generated by intrinsic spinal motor circuits. Such locomotor networks are operational early in development and are found in all vertebrates. This review outlines and compares recent advances...

  15. A Model of Locomotor-Respiratory Coupling in Quadrupeds

    Science.gov (United States)

    Giuliodori,, Mauricio J.; Lujan, Heidi L.; Briggs, Whitney S.; DiCarlo, Stephen E.

    2009-01-01

    Locomotion and respiration are not independent phenomena in running mammals because locomotion and respiration both rely on cyclic movements of the ribs, sternum, and associated musculature. Thus, constraints are imposed on locomotor and respiratory function by virtue of their linkage. Specifically, locomotion imposes mechanical constraints on…

  16. MRT of the locomotor system. 4. rev. and enl. ed.

    International Nuclear Information System (INIS)

    Vahlensieck, Martin; Reiser, Maximilian

    2015-01-01

    The book on MRT of the locomotor system covers the following topics: relevant NMT imaging techniques, spinal cord, shoulder, elbows, wrist and fingers, hip region, knee, lower leg - ankle - foot, temporomandibular joint, skeletal muscles, bone marrow, bone and soft tissue tumors, osteoporosis, sacroiliac joint, jaw and periodontium.

  17. Effects of nutmeg consumption on the open field locomotor activities ...

    African Journals Online (AJOL)

    ... was a steady significant difference (p < 0.05) in the behaviours of line crossing and walling. There was no much significant changes (P<0.05) in the behaviours of hinding, grooming and defeacation between the Treatments and Control groups of animals. Keywords: Nutmeg, Wistar rats, Open field, Locomotor activities ...

  18. Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult.

    Science.gov (United States)

    Rodgers, Shaefali P; Born, Heather A; Das, Pritam; Jankowsky, Joanna L

    2012-06-18

    Transgenic mice expressing disease-associated proteins have become standard tools for studying human neurological disorders. Transgenes are often expressed using promoters chosen to drive continuous high-level expression throughout life rather than temporal and spatial fidelity to the endogenous gene. This approach has allowed us to recapitulate diseases of aging within the two-year lifespan of the laboratory mouse, but has the potential for creating aberrant phenotypes by mechanisms unrelated to the human disorder. We show that overexpression of the Alzheimer's-related amyloid precursor protein (APP) during early postnatal development leads to severe locomotor hyperactivity that can be significantly attenuated by delaying transgene onset until adulthood. Our data suggest that exposure to transgenic APP during maturation influences the development of neuronal circuits controlling motor activity. Both when matched for total duration of APP overexpression and when matched for cortical amyloid burden, animals exposed to transgenic APP as juveniles are more active in locomotor assays than animals in which APP overexpression was delayed until adulthood. In contrast to motor activity, the age of APP onset had no effect on thigmotaxis in the open field as a rough measure of anxiety, suggesting that the interaction between APP overexpression and brain development is not unilateral. Our findings indicate that locomotor hyperactivity displayed by the tet-off APP transgenic mice and several other transgenic models of Alzheimer's disease may result from overexpression of mutant APP during postnatal brain development. Our results serve as a reminder of the potential for unexpected interactions between foreign transgenes and brain development to cause long-lasting effects on neuronal function in the adult. The tet-off APP model provides an easy means of avoiding developmental confounds by allowing transgene expression to be delayed until the mice reach adulthood.

  19. The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

    DEFF Research Database (Denmark)

    Hudson, Brian D; Ulven, Trond; Milligan, Graeme

    2013-01-01

    G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

  20. A Global Assessment of Runoff Sensitivity to Changes in Precipitation, Potential Evaporation, and Other Factors

    OpenAIRE

    Berghuijs, Wouter; Larsen, Joshua; van Emmerik, Tim; Woods, Ross

    2017-01-01

    Precipitation (P) and potential evaporation (Ep) are commonly studied drivers of changing freshwater availability, as aridity (Ep/P) explains ∼90% of the spatial differences in mean runoff across the globe. However, it is unclear if changes in aridity over time are also the most important cause for temporal changes in mean runoff and how this degree of importance varies regionally. We show that previous global assessments that address these questions do not properly account for changes due to...

  1. Exploiting Cross-sensitivity by Bayesian Decoding of Mixed Potential Sensor Arrays

    Energy Technology Data Exchange (ETDEWEB)

    Kreller, Cortney [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-02

    LANL mixed-potential electrochemical sensor (MPES) device arrays were coupled with advanced Bayesian inference treatment of the physical model of relevant sensor-analyte interactions. We demonstrated that our approach could be used to uniquely discriminate the composition of ternary gas sensors with three discreet MPES sensors with an average error of less than 2%. We also observed that the MPES exhibited excellent stability over a year of operation at elevated temperatures in the presence of test gases.

  2. The human transient receptor potential vanilloid 3 channel is sensitized via the ERK pathway

    Czech Academy of Sciences Publication Activity Database

    Vyklická, Lenka; Boukalová, Štěpána; Mačíková, Lucie; Chvojka, Štěpán; Vlachová, Viktorie

    2017-01-01

    Roč. 292, č. 51 (2017), s. 21083-21091 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GA15-15839S Institutional support: RVO:67985823 Keywords : epidermal growth factor receptor (EGFR) * extracellular-signal-regulated kinase (ERK) * keratinocyte * phosphorylation * transient receptor potential channels * TRP channels Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.125, year: 2016

  3. Emotional expectations influence neural sensitivity to fearful faces in humans:An event-related potential study

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The present study tested whether neural sensitivity to salient emotional facial expressions was influenced by emotional expectations induced by a cue that validly predicted the expression of a subsequently presented target face. Event-related potentials (ERPs) elicited by fearful and neutral faces were recorded while participants performed a gender discrimination task under cued (‘expected’) and uncued (‘unexpected’) conditions. The behavioral results revealed that accuracy was lower for fearful compared with neutral faces in the unexpected condition, while accuracy was similar for fearful and neutral faces in the expected condition. ERP data revealed increased amplitudes in the P2 component and 200–250 ms interval for unexpected fearful versus neutral faces. By contrast, ERP responses were similar for fearful and neutral faces in the expected condition. These findings indicate that human neural sensitivity to fearful faces is modulated by emotional expectations. Although the neural system is sensitive to unpredictable emotionally salient stimuli, sensitivity to salient stimuli is reduced when these stimuli are predictable.

  4. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

    2011-11-18

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  5. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    International Nuclear Information System (INIS)

    Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

    2011-01-01

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

  6. Investigation in clinical potential of polarization sensitive optical coherence tomography in laryngeal tumor model study

    Science.gov (United States)

    Zhou, Xin; Oak, Chulho; Ahn, Yeh-Chan; Kim, Sung Won; Tang, Shuo

    2018-02-01

    Polarization-sensitive optical coherence tomography (PS-OCT) is capable of measuring tissue birefringence. It has been widely applied to access the birefringence in tissues such as skin and cartilage. The vocal cord tissue consists of three anatomical layers from the surface to deep inside, the epithelium that contains almost no collagen, the lamina propria that is composed with abundant collagen, and the vocalis muscle layer. Due to the variation in the organization of collagen fibers, the different tissue layers show different tissue birefringence, which can be evaluated by PS-OCT phase retardation measurement. Furthermore, collagen fibers in healthy connective tissues are usually well organized, which provides relatively high birefringence. When the collagen organization is destroyed by diseases such as tumor, the birefringence of the tissue will decrease. In this study, a rabbit laryngeal tumor model with different stages of tumor progression is investigated ex-vivo by PS-OCT. The PS-OCT images show a gradual decrease in birefringence from normal tissue to severe tumor tissue. A phase retardation slope-based analysis is conducted to distinguish the epithelium, lamina propria, and muscle layers, respectively. The phase retardation slope quantifies the birefringence in different layers. The quantitative study provides a more detailed comparison among different stages of the rabbit laryngeal tumor model. The PS-OCT result is validated by the corresponding histology images of the same samples.

  7. Interpreting locomotor biomechanics from the morphology of human footprints.

    Science.gov (United States)

    Hatala, Kevin G; Wunderlich, Roshna E; Dingwall, Heather L; Richmond, Brian G

    2016-01-01

    Fossil hominin footprints offer unique direct windows to the locomotor behaviors of our ancestors. These data could allow a clearer understanding of the evolution of human locomotion by circumventing issues associated with indirect interpretations of habitual locomotor patterns from fossil skeletal material. However, before we can use fossil hominin footprints to understand better the evolution of human locomotion, we must first develop an understanding of how locomotor biomechanics are preserved in, and can be inferred from, footprint morphologies. In this experimental study, 41 habitually barefoot modern humans created footprints under controlled conditions in which variables related to locomotor biomechanics could be quantified. Measurements of regional topography (depth) were taken from 3D models of those footprints, and principal components analysis was used to identify orthogonal axes that described the largest proportions of topographic variance within the human experimental sample. Linear mixed effects models were used to quantify the influences of biomechanical variables on the first five principal axes of footprint topographic variation, thus providing new information on the biomechanical variables most evidently expressed in the morphology of human footprints. The footprint's overall depth was considered as a confounding variable, since biomechanics may be linked to the extent to which a substrate deforms. Three of five axes showed statistically significant relationships with variables related to both locomotor biomechanics and substrate displacement; one axis was influenced only by biomechanics and another only by the overall depth of the footprint. Principal axes of footprint morphological variation were significantly related to gait type (walking or running), kinematics of the hip and ankle joints and the distribution of pressure beneath the foot. These results provide the first quantitative framework for developing hypotheses regarding the

  8. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    Science.gov (United States)

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Potential decadal predictability and its sensitivity to sea ice albedo parameterization in a global coupled model

    Energy Technology Data Exchange (ETDEWEB)

    Koenigk, Torben; Caian, Mihaela; Doescher, Ralf; Wyser, Klaus [Swedish Meteorological and Hydrological Institute, Rossby Centre, Norrkoeping (Sweden); Koenig Beatty, Christof [Universite Catholique de Louvain, Louvain-la-Neuve (Belgium)

    2012-06-15

    Decadal prediction is one focus of the upcoming 5th IPCC Assessment report. To be able to interpret the results and to further improve the decadal predictions it is important to investigate the potential predictability in the participating climate models. This study analyzes the upper limit of climate predictability on decadal time scales and its dependency on sea ice albedo parameterization by performing two perfect ensemble experiments with the global coupled climate model EC-Earth. In the first experiment, the standard albedo formulation of EC-Earth is used, in the second experiment sea ice albedo is reduced. The potential prognostic predictability is analyzed for a set of oceanic and atmospheric parameters. The decadal predictability of the atmospheric circulation is small. The highest potential predictability was found in air temperature at 2 m height over the northern North Atlantic and the southern South Atlantic. Over land, only a few areas are significantly predictable. The predictability for continental size averages of air temperature is relatively good in all northern hemisphere regions. Sea ice thickness is highly predictable along the ice edges in the North Atlantic Arctic Sector. The meridional overturning circulation is highly predictable in both experiments and governs most of the decadal climate predictability in the northern hemisphere. The experiments using reduced sea ice albedo show some important differences like a generally higher predictability of atmospheric variables in the Arctic or higher predictability of air temperature in Europe. Furthermore, decadal variations are substantially smaller in the simulations with reduced ice albedo, which can be explained by reduced sea ice thickness in these simulations. (orig.)

  10. Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel

    Czech Academy of Sciences Publication Activity Database

    Maršáková, Lenka; Touška, Filip; Krůšek, Jan; Vlachová, Viktorie

    2012-01-01

    Roč. 116, č. 4 (2012), s. 903-917 ISSN 0003-3022 R&D Projects: GA ČR(CZ) GA305/09/0081; GA ČR(CZ) GA202/09/0806; GA ČR(CZ) GD305/08/H037; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GBP304/12/G069 Grant - others:Univerzita Karlova(CZ) 25409 Institutional research plan: CEZ:AV0Z50110509 Keywords : vanilloid receptor * camphor * transient receptor potential Subject RIV: ED - Physiology Impact factor: 5.163, year: 2012

  11. Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO{sub 2} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Choi, Byeong Hyeok; Son, Sang Wook [Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul (Korea, Republic of); Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2011-07-06

    The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO{sub 2} nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO{sub 2} nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

  12. Insulin Signaling in Bupivacaine-induced Cardiac Toxicity: Sensitization during Recovery and Potentiation by Lipid Emulsion

    Science.gov (United States)

    Fettiplace, Michael R.; Kowal, Katarzyna; Ripper, Richard; Young, Alexandria; Lis, Kinga; Rubinstein, Israel; Bonini, Marcelo; Minshall, Richard; Weinberg, Guy

    2015-01-01

    Background The impact of local anesthetics on regulation of glucose homeostasis by protein kinase B (Akt) and 5’-Adenosine monophosphate activated protein kinase (AMPK) is unclear but important because of the implications for both local anesthetic toxicity and its reversal by intravenous lipid emulsion (ILE). Methods Sprague-Dawley rats received 10mg/kg bupivacaine over 20 seconds followed by nothing or 10mL/kg ILE (or ILE without bupivacaine). At key time points, heart and kidney were excised. Glycogen content and phosphorylation levels of Akt, p70s6k, s6, IRS1, GSK-3β, AMPK, ACC, TSC2 were quantified. Three animals received Wortmannin to irreversibily inhibit phosphoinositide-3-kinase (Pi3k) signaling. Isolated heart studies were conducted with bupivacaine and LY294002—a reversible Pi3K inhibitor. Results Bupivacaine cardiotoxicity rapidly de-phosphorylated Akt at S473 to 63 ± 5% of baseline and phosphorylated AMPK to 151 ± 19%. AMPK activation inhibited targets downstream of mTORC1 via TSC2. Feedback dephosphorylation of IRS1 to 31 ± 8% of baseline sensitized Akt signaling in hearts resulting in hyper-phosphorylation of Akt at T308 and GSK-3β to 390 ± 64% and 293 ± 50% of baseline respectively. Glycogen accumulated to 142 ± 7% of baseline. Irreversible inhibition of Pi3k upstream of Akt exacerbated bupivacaine cardiotoxicity, while pretreating with a reversible inhibitor delayed onset of toxicity. ILE rapidly phosphorylated Akt at S473 and T308 to 150 ± 23% and 167 ± 10% of baseline, respectively but did not interfere with AMPK or targets of mTORC1. Conclusion Glucose handling by Akt and AMPK is integral to recovery from bupivacaine cardiotoxicity and modulation of these pathways by ILE contributes to lipid resuscitation. PMID:26646023

  13. Aquifer heterogeneity characterization with oscillatory pumping: Sensitivity analysis and imaging potential

    Science.gov (United States)

    Cardiff, M.; Bakhos, T.; Kitanidis, P. K.; Barrash, W.

    2013-09-01

    Periodic pumping tests, in which a fluid is extracted during half a period, then reinjected, have been used historically to estimate effective aquifer properties. In this work, we suggest a modified approach to periodic pumping test analysis in which one uses several periodic pumping signals of different frequencies as stimulation, and responses are analyzed through inverse modeling using a "steady-periodic" model formulation. We refer to this strategy as multifrequency oscillatory hydraulic imaging. Oscillating pumping tests have several advantages that have been noted, including no net water extraction during testing and robust signal measurement through signal processing. Through numerical experiments, we demonstrate additional distinct advantages that multifrequency stimulations have, including: (1) drastically reduced computational cost through use of a steady-periodic numerical model and (2) full utilization of the aquifer heterogeneity information provided by responses at different frequencies. We first perform fully transient numerical modeling for heterogeneous aquifers and show that equivalent results are obtained using a faster steady-periodic heterogeneous numerical model of the wave phasor. The sensitivities of observed signal response to aquifer heterogeneities are derived using an adjoint state-based approach, which shows that different frequency stimulations provide complementary information. Finally, we present an example 2-D application in which sinusoidal signals at multiple frequencies are used as a data source and are inverted to obtain estimates of aquifer heterogeneity. These analyses show the different heterogeneity information that can be obtained from different stimulation frequencies, and that data from several sinusoidal pumping tests can be rapidly inverted using the steady-periodic framework.

  14. In vivo potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by the radiation sensitizer benznidazole

    International Nuclear Information System (INIS)

    Siemann, D.W.; Morrissey, S.; Wolf, K.

    1983-01-01

    Recent studies in mouse tumor systems have indicated a potential therapeutic advantage in combining the radiosensitizer misonidazole (MISO) with cancer chemotherapy drugs. One agent the antitumor activity of which has been enhanced to a greater extent than its hematological or gastrointestinal toxicities is the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Recently, sensitizers more lipophylic than MISO have been reported to give greater tumor response enhancement when combined with CCNU. The present studies compared the potential therapeutic benefit of combining MISO (partition coefficient, 0.43) or benznidazole (BENZO) (partition coefficient, 8.5) in KHT sarcoma or RIF-1 tumor-bearing C3H mice. Both sensitizers were administered i.p. and given either 30 min before (BENZO) or simultaneously with (MISO) the chemotherapeutic agent. Survival of clonogenic tumor cells assessed 22 to 24 hr after treatment or in situ tumor growth delay were used as assays of tumor response. Normal tissue toxicity was determined using the drug dose yielding 50% animal lethality in 30 days end point. When combined with CCNU, doses of MISO (5.0 mmol/kg) or BENZO (0.3 mmol/kg) were found to yield approximately equivalent increases in both the tumor effect (enhancement ratio, approximately 1.8 to 2.0) and normal tissue toxicity (enhancement ratio approximately 1.3 to 1.4). Both sensitizers therefore led to a therapeutic benefit. However, although a approximately 10-fold lower dose of the more lipophylic sensitizer BENZO proved to be as effective as MISO at enhancing the tumoricidal effects of CCNU, this dose reduction did not result in a greater therapeutic gain for BENZO

  15. A simple behavioral test for locomotor function after brain injury in mice.

    Science.gov (United States)

    Tabuse, Masanao; Yaguchi, Masae; Ohta, Shigeki; Kawase, Takeshi; Toda, Masahiro

    2010-11-01

    To establish a simple and reliable test for assessing locomotor function in mice with brain injury, we developed a new method, the rotarod slip test, in which the number of slips of the paralytic hind limb from a rotarod is counted. Brain injuries of different severity were created in adult C57BL/6 mice, by inflicting 1-point, 2-point and 4-point cryo-injuries. These mice were subjected to the rotarod slip test, the accelerating rotarod test and the elevated body swing test (EBST). Histological analyses were performed to assess the severity of the brain damage. Significant and consistent correlations between test scores and severity were observed for the rotarod slip test and the EBST. Only the rotarod slip test detected the mild hindlimb paresis in the acute and sub-acute phase after injury. Our results suggest that the rotarod slip test is the most sensitive and reliable method for assessing locomotor function after brain damage in mice. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

    Science.gov (United States)

    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues.

  17. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  18. Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis.

    Science.gov (United States)

    Daly, Michael J; Finlay, Dewar D; Guldenring, Daniel; Bond, Raymond R; McCann, Aaron J; Scott, Peter J; Adgey, Jennifer A; Harbinson, Mark T

    2017-12-01

    Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI). Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L. Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m 2 . Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90

  19. Distinct sets of locomotor modules control the speed and modes of human locomotion

    Science.gov (United States)

    Yokoyama, Hikaru; Ogawa, Tetsuya; Kawashima, Noritaka; Shinya, Masahiro; Nakazawa, Kimitaka

    2016-01-01

    Although recent vertebrate studies have revealed that different spinal networks are recruited in locomotor mode- and speed-dependent manners, it is unknown whether humans share similar neural mechanisms. Here, we tested whether speed- and mode-dependence in the recruitment of human locomotor networks exists or not by statistically extracting locomotor networks. From electromyographic activity during walking and running over a wide speed range, locomotor modules generating basic patterns of muscle activities were extracted using non-negative matrix factorization. The results showed that the number of modules changed depending on the modes and speeds. Different combinations of modules were extracted during walking and running, and at different speeds even during the same locomotor mode. These results strongly suggest that, in humans, different spinal locomotor networks are recruited while walking and running, and even in the same locomotor mode different networks are probably recruited at different speeds. PMID:27805015

  20. Eating high fat chow decreases dopamine clearance in adolescent and adult male rats but selectively enhances the locomotor stimulating effects of cocaine in adolescents.

    Science.gov (United States)

    Baladi, Michelle G; Horton, Rebecca E; Owens, William A; Daws, Lynette C; France, Charles P

    2015-03-24

    Feeding conditions can influence dopamine neurotransmission and impact behavioral and neurochemical effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters the locomotor effects of cocaine and dopamine transporter activity in adolescent (postnatal day 25) and adult (postnatal day 75) male Sprague-Dawley rats. Dose-response curves for cocaine-induced locomotor activity were generated in rats with free access to either standard or high fat chow or restricted access to high fat chow (body weight matched to rats eating standard chow). Compared with eating standard chow, eating high fat chow increased the sensitivity of adolescent, but not adult, rats to the acute effects of cocaine. When tested once per week, sensitization to the locomotor effects of cocaine was enhanced in adolescent rats eating high fat chow compared with adolescent rats eating standard chow. Sensitization to cocaine was not different among feeding conditions in adults. When adolescent rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. As measured by chronoamperometry, dopamine clearance rate in striatum was decreased in both adolescent and adult rats eating high fat chow compared with age-matched rats eating standard chow. These results suggest that high fat diet-induced reductions in dopamine clearance rate do not always correspond to increased sensitivity to the locomotor effects of cocaine, suggesting that mechanisms other than dopamine transporter might play a role. Moreover, in adolescent but not adult rats, eating high fat chow increases sensitivity to cocaine and enhances the sensitization that develops to cocaine. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  1. Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer

    International Nuclear Information System (INIS)

    Xia, Xi; Weng, Yanjie; Liao, Shujie; Han, Zhiqiang; Liu, Ronghua; Zhu, Tao; Wang, Shixuan; Xu, Gang; Meng, Li; Zhou, Jianfeng; Ma, Ding; Ma, Quanfu; Li, Xiao; Ji, Teng; Chen, Pingbo; Xu, Hongbin; Li, Kezhen; Fang, Yong; Weng, Danhui

    2011-01-01

    P21 (WAF1/Cip1) binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer. RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry. p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment. Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment

  2. Sensitivity of aquatic organisms to ethanol and its potential use as bioindicators

    Directory of Open Access Journals (Sweden)

    Adilson Ferreira Silva

    2016-12-01

    Full Text Available The aim of this research was to evaluate the feasibility for the use of the organisms Lemna minor, Azolla caroliniana, Hyphessobrycon eques, Pomacea canaliculata and Daphnia magna as exposure bioindicators for ethanol (lethal and effective concentration 50% - LC50(I/EC50(I. Thus, the following concentrations were used 5.0; 10.0; 20.0; 30.0; 40.0 and 50.0 mg L-1 ethanol on L. minor; 25.0; 50.0; 75.0; 100.0; 150.0 and 200.0 mg L-1 on A. caroliniana; 0.3; 0.5; 1.0; 2.0 and 3.0 mg L-1 on H. eques; 0.05; 0.10; 0.20; 0.40 and 0.80 mg L-1 on P. canaliculata; and 40.0; 60.0; 80.0; 100.0; 120.0 and 140.0 mg L-1 on D. magna. An untreated control was also kept for all organisms, with three repetitions. The increase in the ethanol concentration elevated the electrical conductivity and decreased the water dissolved oxygen and pH. The ethanol LC50 for L. minor and A. caroliniana were 12.78 and 73.11 mg L-1, respectively, and was classified as slightly toxic; 1.22 mg L-1 for H. eques (moderately toxic; 0.39 mg L-1 for P. canaliculata (highly toxic and 98.85 mg L-1 for D. magna (slightly toxic. Thus, H. eques and P. canaliculata have showed good potential for the use as ethanol exposure bioindicators on water bodies.

  3. Spatial profile measurements of ion-confining potentials using novel position-sensitive ion-energy spectrometer arrays

    International Nuclear Information System (INIS)

    Yoshida, M.; Cho, T.; Hirata, M.; Ito, H.; Kohagura, J.; Yatsu, K.; Miyoshi, S.

    2003-01-01

    The first experimental demonstration of simultaneous measurements of temporally and spatially resolved ion-confining potentials phi c and end-loss-ion fluxes I ELA has been carried out during a single plasma discharge alone by the use of newly designed ion-energy-spectrometer arrays installed in both end regions of the GAMMA 10 tandem mirror. This position-sensitive ion-detector structure is proposed to obtain precise ion-energy spectra without any perturbations from simultaneously incident energetic electrons into the arrays. The relation between phi c and I ELA is physically interpreted in terms of Pastukhov's potential confinement theory. In particular, the importance of axisymmetric phi c formation is found for the plasma confinement

  4. Evaluation of a high-throughput peptide reactivity format assay for assessment of the skin sensitization potential of chemicals

    Directory of Open Access Journals (Sweden)

    Chin Lin eWong

    2016-03-01

    Full Text Available The direct peptide reactivity assay (DPRA is a validated method for in vitro assessment of the skin sensitization potential of chemicals. In the present work, we describe a peptide reactivity assay using 96-well plate format and systematically identified the optimal assay conditions for accurate and reproducible classification of chemicals with known sensitizing capacity. The aim of the research is to ensure that the analytical component of the peptide reactivity assay is robust, accurate and reproducible in accordance with criteria that are used for the validation of bioanalytical methods. Analytical performance was evaluated using quality control samples (QCs; heptapeptides at low, medium and high concentrations and incubation of control chemicals (chemicals with known sensitization capacity, weak, moderate, strong, extreme and non-sensitizers with each of three synthetic heptapeptides, viz Cor1-C420 (Ac-NKKCDLF, cysteine- (Ac-RFAACAA and lysine- (Ac-RFAAKAA containing heptapeptides. The optimal incubation temperature for all three heptapeptides was 25°C. Apparent heptapeptide depletion was affected by vial material composition. Incubation of test chemicals with Cor1-C420, showed that peptide depletion was unchanged in polypropylene vials over 3-days storage in an autosampler but this was not the case for borosilicate glass vials. For cysteine-containing heptapeptide, the concentration was not stable by day 3 post-incubation in borosilicate glass vials. Although the lysine-containing heptapeptide concentration was unchanged in both polypropylene and borosilicate glass vials, the apparent extent of lysine-containing heptapeptide depletion by ethyl acrylate, differed between polypropylene (24.7% and glass (47.3% vials. Additionally, the peptide-chemical complexes for Cor1-C420-cinnamaldehyde and cysteine-containing heptapeptide-2,4-dinitrochlorobenzene were partially reversible during 3-days of autosampler storage. These observations further

  5. Effects of repeated exposure to malathion on growth, food consumption, and locomotor performance of the western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    Holem, Ryan R. [University of Georgia, Savannah River Ecology Laboratory, Aiken, SC 29801 (United States); ENTRIX, Inc., Okemos, MI 48864 (United States); Hopkins, William A. [University of Georgia, Savannah River Ecology Laboratory, Aiken, SC 29801 (United States); Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States)], E-mail: hopkinsw@vt.edu; Talent, Larry G. [Natural Resource Ecology and Management, Oklahoma State University, Stillwater, OK 74078 (United States)

    2008-03-15

    Effects of repeated pollutant exposure on growth, locomotor performance, and behavior have rarely been evaluated in reptiles. We administered three doses of malathion (2.0, 20, or 100 mg/kg body weight) to western fence lizards (Sceloporus occidentalis) over an 81 day period. Eight and 23% mortality occurred at 20 and 100 mg/kg (p = 0.079) and 85% of lizards in the 100 mg/kg group exhibited clinical symptoms of poisoning. Growth, food consumption, body condition index, and terrestrial locomotor performance were not significantly influenced by malathion. However, arboreal sprint velocity was significantly reduced in lizards receiving 100 mg/kg. Fifty percent of lizards in the 100 mg/kg group also refused to sprint in the arboreal setting (p = 0.085). Based on these results, arboreal locomotor performance was the most sensitive metric of exposure we evaluated. Further study of compounds such as malathion is warranted due to highly variable application rates and exposure scenarios. - Repeated exposure of western fence lizards to malathion caused reduced arboreal performance and some mortality but growth, food consumption, and terrestrial performance were not affected.

  6. Effects of repeated exposure to malathion on growth, food consumption, and locomotor performance of the western fence lizard (Sceloporus occidentalis)

    International Nuclear Information System (INIS)

    Holem, Ryan R.; Hopkins, William A.; Talent, Larry G.

    2008-01-01

    Effects of repeated pollutant exposure on growth, locomotor performance, and behavior have rarely been evaluated in reptiles. We administered three doses of malathion (2.0, 20, or 100 mg/kg body weight) to western fence lizards (Sceloporus occidentalis) over an 81 day period. Eight and 23% mortality occurred at 20 and 100 mg/kg (p = 0.079) and 85% of lizards in the 100 mg/kg group exhibited clinical symptoms of poisoning. Growth, food consumption, body condition index, and terrestrial locomotor performance were not significantly influenced by malathion. However, arboreal sprint velocity was significantly reduced in lizards receiving 100 mg/kg. Fifty percent of lizards in the 100 mg/kg group also refused to sprint in the arboreal setting (p = 0.085). Based on these results, arboreal locomotor performance was the most sensitive metric of exposure we evaluated. Further study of compounds such as malathion is warranted due to highly variable application rates and exposure scenarios. - Repeated exposure of western fence lizards to malathion caused reduced arboreal performance and some mortality but growth, food consumption, and terrestrial performance were not affected

  7. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

    Science.gov (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

    2017-10-04

    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

  8. Assessment of the Potential Impacts of Wheat Plant Traits across Environments by Combining Crop Modeling and Global Sensitivity Analysis

    Science.gov (United States)

    Casadebaig, Pierre; Zheng, Bangyou; Chapman, Scott; Huth, Neil; Faivre, Robert; Chenu, Karine

    2016-01-01

    A crop can be viewed as a complex system with outputs (e.g. yield) that are affected by inputs of genetic, physiology, pedo-climatic and management information. Application of numerical methods for model exploration assist in evaluating the major most influential inputs, providing the simulation model is a credible description of the biological system. A sensitivity analysis was used to assess the simulated impact on yield of a suite of traits involved in major processes of crop growth and development, and to evaluate how the simulated value of such traits varies across environments and in relation to other traits (which can be interpreted as a virtual change in genetic background). The study focused on wheat in Australia, with an emphasis on adaptation to low rainfall conditions. A large set of traits (90) was evaluated in a wide target population of environments (4 sites × 125 years), management practices (3 sowing dates × 3 nitrogen fertilization levels) and CO2 (2 levels). The Morris sensitivity analysis method was used to sample the parameter space and reduce computational requirements, while maintaining a realistic representation of the targeted trait × environment × management landscape (∼ 82 million individual simulations in total). The patterns of parameter × environment × management interactions were investigated for the most influential parameters, considering a potential genetic range of +/- 20% compared to a reference cultivar. Main (i.e. linear) and interaction (i.e. non-linear and interaction) sensitivity indices calculated for most of APSIM-Wheat parameters allowed the identification of 42 parameters substantially impacting yield in most target environments. Among these, a subset of parameters related to phenology, resource acquisition, resource use efficiency and biomass allocation were identified as potential candidates for crop (and model) improvement. PMID:26799483

  9. Assessment of the Potential Impacts of Wheat Plant Traits across Environments by Combining Crop Modeling and Global Sensitivity Analysis.

    Directory of Open Access Journals (Sweden)

    Pierre Casadebaig

    Full Text Available A crop can be viewed as a complex system with outputs (e.g. yield that are affected by inputs of genetic, physiology, pedo-climatic and management information. Application of numerical methods for model exploration assist in evaluating the major most influential inputs, providing the simulation model is a credible description of the biological system. A sensitivity analysis was used to assess the simulated impact on yield of a suite of traits involved in major processes of crop growth and development, and to evaluate how the simulated value of such traits varies across environments and in relation to other traits (which can be interpreted as a virtual change in genetic background. The study focused on wheat in Australia, with an emphasis on adaptation to low rainfall conditions. A large set of traits (90 was evaluated in a wide target population of environments (4 sites × 125 years, management practices (3 sowing dates × 3 nitrogen fertilization levels and CO2 (2 levels. The Morris sensitivity analysis method was used to sample the parameter space and reduce computational requirements, while maintaining a realistic representation of the targeted trait × environment × management landscape (∼ 82 million individual simulations in total. The patterns of parameter × environment × management interactions were investigated for the most influential parameters, considering a potential genetic range of +/- 20% compared to a reference cultivar. Main (i.e. linear and interaction (i.e. non-linear and interaction sensitivity indices calculated for most of APSIM-Wheat parameters allowed the identification of 42 parameters substantially impacting yield in most target environments. Among these, a subset of parameters related to phenology, resource acquisition, resource use efficiency and biomass allocation were identified as potential candidates for crop (and model improvement.

  10. Assessment of the Potential Impacts of Wheat Plant Traits across Environments by Combining Crop Modeling and Global Sensitivity Analysis.

    Science.gov (United States)

    Casadebaig, Pierre; Zheng, Bangyou; Chapman, Scott; Huth, Neil; Faivre, Robert; Chenu, Karine

    2016-01-01

    A crop can be viewed as a complex system with outputs (e.g. yield) that are affected by inputs of genetic, physiology, pedo-climatic and management information. Application of numerical methods for model exploration assist in evaluating the major most influential inputs, providing the simulation model is a credible description of the biological system. A sensitivity analysis was used to assess the simulated impact on yield of a suite of traits involved in major processes of crop growth and development, and to evaluate how the simulated value of such traits varies across environments and in relation to other traits (which can be interpreted as a virtual change in genetic background). The study focused on wheat in Australia, with an emphasis on adaptation to low rainfall conditions. A large set of traits (90) was evaluated in a wide target population of environments (4 sites × 125 years), management practices (3 sowing dates × 3 nitrogen fertilization levels) and CO2 (2 levels). The Morris sensitivity analysis method was used to sample the parameter space and reduce computational requirements, while maintaining a realistic representation of the targeted trait × environment × management landscape (∼ 82 million individual simulations in total). The patterns of parameter × environment × management interactions were investigated for the most influential parameters, considering a potential genetic range of +/- 20% compared to a reference cultivar. Main (i.e. linear) and interaction (i.e. non-linear and interaction) sensitivity indices calculated for most of APSIM-Wheat parameters allowed the identification of 42 parameters substantially impacting yield in most target environments. Among these, a subset of parameters related to phenology, resource acquisition, resource use efficiency and biomass allocation were identified as potential candidates for crop (and model) improvement.

  11. Usability evaluation of a locomotor therapy device considering different strategies

    Directory of Open Access Journals (Sweden)

    Langthaler Sonja

    2016-09-01

    Full Text Available Usability of medical devices is one of the main determining factors in preventing use errors in treatment and strongly correlates to patient safety and quality of treatment. This thesis demonstrates the usability testing and evaluation of a prototype for locomotor therapy of infants. Therefore, based on the normative requirements of the EN 62366, a concept combined of evaluation procedures and assessing methods was created to enable extensive testing and analysis of the different aspects of usability. On the basis of gathered information weak points were identified and appropriate measures were presented to increase the usability and operating safety of the locomotor prototype. The overall outcome showed an usability value of 77.4% and an evaluation score of 6.99, which can be interpreted as “satisfactory”.

  12. The peacock train does not handicap cursorial locomotor performance

    Science.gov (United States)

    Thavarajah, Nathan K.; Tickle, Peter G.; Nudds, Robert L.; Codd, Jonathan R.

    2016-01-01

    Exaggerated traits, like the peacock train, are recognized as classic examples of sexual selection. The evolution of sexual traits is often considered paradoxical as, although they enhance reproductive success, they are widely presumed to hinder movement and survival. Many exaggerated traits represent an additional mechanical load that must be carried by the animal and therefore may influence the metabolic cost of locomotion and constrain locomotor performance. Here we conducted respirometry experiments on peacocks and demonstrate that the exaggerated sexually selected train does not compromise locomotor performance in terms of the metabolic cost of locomotion and its kinematics. Indeed, peacocks with trains had a lower absolute and mass specific metabolic cost of locomotion. Our findings suggest that adaptations that mitigate any costs associated with exaggerated morphology are central in the evolution of sexually selected traits. PMID:27805067

  13. Structural attributes contributing to locomotor performance in the ostrich

    OpenAIRE

    Schaller, Nina U.

    2008-01-01

    As the fastest long-endurance runner, the bipedal ostrich (Struthio camelus) was selected as a prime model organism to investigate the physical attributes underlying this advanced locomotor performance. A specific integrative approach combining morphological, morphometric, kinematic and pedobarographic methods was developed. The comparative morphometric analysis of the hind limbs of all ratite species revealed that leg segment ratios in the ostrich are the most specialised for efficient locom...

  14. Muscle Spindles and Locomotor Control-An Unrecognized Falls Determinant?

    OpenAIRE

    Marks Ray

    2015-01-01

    BACKGROUND: Historically, evidence muscle spindles might be involved in locomotion was provided by their presence in tetrapod antigravity muscles associated with posture and locomotion. Later, Brodal (1962) noted muscle spindles in all muscles of locomotion. To unravel the complexity of the muscle spindle and its role in human locomotor control many investigators have since conducted lesion and/or anaesthesia studies in subhuman species and human contexts. QUESTIONS: How ...

  15. Locomotor Sub-functions for Control of Assistive Wearable Robots

    OpenAIRE

    Sharbafi, Maziar A.; Seyfarth, Andre; Zhao, Guoping

    2017-01-01

    A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated:...

  16. Locomotor therapy with extended-release crystalline glucocorticoids

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available Topical glucocorticoid (GC therapy for locomotor diseases is an extremely important component of a comprehensive program to treat inflammatory and, to a lesser extent, degenerative diseases. It reduces the time of hospitalization by 5—10 days in this category of patients, has a prompt and potent anti-inflammatory effect, and shows predictable efficiency. This therapy shows good tolerability and high safety and prevents serious adverse reactions to GC treatment.

  17. Limitations imposed by wearing armour on Medieval soldiers' locomotor performance

    OpenAIRE

    Askew, Graham N.; Formenti, Federico; Minetti, Alberto E.

    2011-01-01

    In Medieval Europe, soldiers wore steel plate armour for protection during warfare. Armour design reflected a trade-off between protection and mobility it offered the wearer. By the fifteenth century, a typical suit of field armour weighed between 30 and 50 kg and was distributed over the entire body. How much wearing armour affected Medieval soldiers' locomotor energetics and biomechanics is unknown. We investigated the mechanics and the energetic cost of locomotion in armour, and determined...

  18. Learning a locomotor task: with or without errors?

    Science.gov (United States)

    Marchal-Crespo, Laura; Schneider, Jasmin; Jaeger, Lukas; Riener, Robert

    2014-03-04

    Robotic haptic guidance is the most commonly used robotic training strategy to reduce performance errors while training. However, research on motor learning has emphasized that errors are a fundamental neural signal that drive motor adaptation. Thus, researchers have proposed robotic therapy algorithms that amplify movement errors rather than decrease them. However, to date, no study has analyzed with precision which training strategy is the most appropriate to learn an especially simple task. In this study, the impact of robotic training strategies that amplify or reduce errors on muscle activation and motor learning of a simple locomotor task was investigated in twenty two healthy subjects. The experiment was conducted with the MAgnetic Resonance COmpatible Stepper (MARCOS) a special robotic device developed for investigations in the MR scanner. The robot moved the dominant leg passively and the subject was requested to actively synchronize the non-dominant leg to achieve an alternating stepping-like movement. Learning with four different training strategies that reduce or amplify errors was evaluated: (i) Haptic guidance: errors were eliminated by passively moving the limbs, (ii) No guidance: no robot disturbances were presented, (iii) Error amplification: existing errors were amplified with repulsive forces, (iv) Noise disturbance: errors were evoked intentionally with a randomly-varying force disturbance on top of the no guidance strategy. Additionally, the activation of four lower limb muscles was measured by the means of surface electromyography (EMG). Strategies that reduce or do not amplify errors limit muscle activation during training and result in poor learning gains. Adding random disturbing forces during training seems to increase attention, and therefore improve motor learning. Error amplification seems to be the most suitable strategy for initially less skilled subjects, perhaps because subjects could better detect their errors and correct them

  19. Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

    Directory of Open Access Journals (Sweden)

    Andrea Maesani

    2015-11-01

    Full Text Available The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior.

  20. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton

    Science.gov (United States)

    Kinnaird, Catherine R.; Ferris, Daniel P.

    2013-01-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to “fight” the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations. PMID:23307949

  1. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton.

    Science.gov (United States)

    Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P

    2013-04-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations.

  2. Activation of the GABAB receptor prevents nicotine-induced locomotor stimulation in mice

    Directory of Open Access Journals (Sweden)

    Carla eLobina

    2011-12-01

    Full Text Available Recent studies demonstrated that activation of the GABAB receptor, either by means of orthosteric agonists or positive allosteric modulators (PAMs, inhibited different nicotine-related behaviors, including intravenous self-administration and conditioned place preference, in rodents. The present study investigated whether the anti-nicotine effects of the GABAB receptor agonist, baclofen, and GABAB PAMs, CGP7930 and GS39783, extend to nicotine stimulant effects. To this end, CD1 mice were initially treated with baclofen (0, 1.25, and 2.5 mg/kg, i.p., CGP7930 (0, 25, and 50 mg/kg, i.g., or GS39783 (0, 25, and 50 mg/kg, i.g., then treated with nicotine (0 and 0.05 mg/kg, s.c., and finally exposed to an automated apparatus for recording of locomotor activity. Pretreatment with doses of baclofen, CGP7930, or GS39783 that did not alter locomotor activity when given with nicotine vehicle fully prevented hyperlocomotion induced by 0.05 mg/kg nicotine. These data extend to nicotine stimulant effects the capacity of baclofen and GABAB PAMs to block the reinforcing, motivational, and rewarding properties of nicotine. These data strengthen the hypothesis that activation of the GABAB receptor may represent a potentially useful, anti-smoking therapeutic strategy.

  3. Circadian locomotor rhythms in the cricket, Gryllodes sigillatus. II. Interactions between bilaterally paired circadian pacemakers.

    Science.gov (United States)

    Ushirogawa, H; Abe, Y; Tomioka, K

    1997-10-01

    The optic lobe is essential for circadian locomotor rhythms in the cricket, Gryllodes sigillatus. We examined potential interactions between the bilaterally paired optic lobes in circadian rhythm generation. When one optic lobe was removed, the free-running period of the locomotor rhythm slightly but significantly lengthened. When exposed to light-dark cycles (LD) with 26 hr period, intact and sham operated animals were clearly entrained to the light cycle, but a large number of animals receiving unilateral optic nerve severance showed rhythm dissociation. In the dissociation, two rhythmic components appeared; one was readily entrained to the given LD and the other free-ran with a period shorter than 24 hr, and activity was expressed only when they were inphase. The period of the free-running component was significantly longer than that of the animals with a single blinded pacemaker kept in LD13:13, suggesting that the pacemaker on the intact side had some influence on the blinded pacemaker even in the dissociated state. The ratio of animals with rhythm dissociation was greater with the lower light intensity of the LD. The results suggest that the bilaterally distributed pacemakers are only weakly coupled to one another but strongly suppress the activity driven by the partner pacemaker during their subjective day. The strong suppression of activity would be advantageous to keep a stable nocturnality for this cricket living indoors.

  4. Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

    Science.gov (United States)

    Fakhoury, Marc

    2015-01-01

    Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

  5. The Influence of Shape on the Output Potential of ZnO Nanostructures: Sensitivity to Parallel versus Perpendicular Forces

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    José Cardoso

    2018-05-01

    Full Text Available With the consistent shrinking of devices, micro-systems are, nowadays, widely used in areas such as biomedics, electronics, automobiles, and measurement devices. As devices shrunk, so too did their energy consumptions, opening the way for the use of nanogenerators (NGs as power sources. In particular, to harvest energy from an object’s motion (mechanical vibrations, torsional forces, or pressure, present NGs are mainly composed of piezoelectric materials in which, upon an applied compressive or strain force, an electrical field is produced that can be used to power a device. The focus of this work is to simulate the piezoelectric effect in different ZnO nanostructures to optimize the output potential generated by a nanodevice. In these simulations, cylindrical nanowires, nanomushrooms, and nanotrees were created, and the influence of the nanostructures’ shape on the output potential was studied as a function of applied parallel and perpendicular forces. The obtained results demonstrated that the output potential is linearly proportional to the applied force and that perpendicular forces are more efficient in all structures. However, nanotrees were found to have an increased sensitivity to parallel applied forces, which resulted in a large enhancement of the output efficiency. These results could then open a new path to increase the efficiency of piezoelectric nanogenerators.

  6. Ontogenetic development of the inner ear saccule and utricle in the Lusitanian toadfish: Potential implications for auditory sensitivity.

    Science.gov (United States)

    Chaves, Patrícia P; Valdoria, Ciara M C; Amorim, M Clara P; Vasconcelos, Raquel O

    2017-09-01

    Studies addressing structure-function relationships of the fish auditory system during development are sparse compared to other taxa. The Batrachoididae has become an important group to investigate mechanisms of auditory plasticity and evolution of auditory-vocal systems. A recent study reported ontogenetic improvements in the inner ear saccule sensitivity of the Lusitanian toadfish, Halobatrachus didactylus, but whether this results from changes in the sensory morphology remains unknown. We investigated how the macula and organization of auditory receptors in the saccule and utricle change during growth in this species. Inner ear sensory epithelia were removed from the end organs of previously PFA-fixed specimens, from non-vocal posthatch fry (23 cm). Epithelia were phalloidin-stained and analysed for area, shape, number and orientation patterns of hair cells (HC), and number and size of saccular supporting cells (SC). Saccular macula area expanded 41x in total, and significantly more (relative to body length) among vocal juveniles (2.3-2.9 cm). Saccular HC number increased 25x but HC density decreased, suggesting that HC addition is slower relative to epithelial growth. While SC density decreased, SC apical area increased, contributing to the epithelial expansion. The utricule revealed increased HC density (striolar region) and less epithelial expansion (5x) with growth, contrasting with the saccule that may have a different developmental pattern due to its larger size and main auditory functions. Both macula shape and HC orientation patterns were already established in the posthatch fry and retained throughout growth in both end organs. We suggest that previously reported ontogenetic improvements in saccular sensitivity might be associated with changes in HC number (not density), size and/or molecular mechanisms controlling HC sensitivity. This is one of the first studies investigating the ontogenetic development of the saccule and utricle in a vocal fish and

  7. Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity

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    Samira Alliouachene

    2015-12-01

    Full Text Available In contrast to the class I phosphoinositide 3-kinases (PI3Ks, the organismal roles of the kinase activity of the class II PI3Ks are less clear. Here, we report that class II PI3K-C2β kinase-dead mice are viable and healthy but display an unanticipated enhanced insulin sensitivity and glucose tolerance, as well as protection against high-fat-diet-induced liver steatosis. Despite having a broad tissue distribution, systemic PI3K-C2β inhibition selectively enhances insulin signaling only in metabolic tissues. In a primary hepatocyte model, basal PI3P lipid levels are reduced by 60% upon PI3K-C2β inhibition. This results in an expansion of the very early APPL1-positive endosomal compartment and altered insulin receptor trafficking, correlating with an amplification of insulin-induced, class I PI3K-dependent Akt signaling, without impacting MAPK activity. These data reveal PI3K-C2β as a critical regulator of endosomal trafficking, specifically in insulin signaling, and identify PI3K-C2β as a potential drug target for insulin sensitization.

  8. The effect of panic disorder versus anxiety sensitivity on event-related potentials during anticipation of threat.

    Science.gov (United States)

    Stevens, Elizabeth S; Weinberg, Anna; Nelson, Brady D; Meissel, Emily E E; Shankman, Stewart A

    2018-03-01

    Attention-related abnormalities are key components of the abnormal defensive responding observed in panic disorder (PD). Although behavioral studies have found aberrant attentional biases towards threat in PD, psychophysiological studies have been mixed. Predictability of threat, an important feature of threat processing, may have contributed to these mixed findings. Additionally, anxiety sensitivity, a dimensional trait associated with PD, may yield stronger associations with cognitive processes than categorical diagnoses of PD. In this study, 171 participants with PD and/or depression and healthy controls completed a task that differentiated anticipation of predictable vs. unpredictable shocks, while startle eyeblink and event-related potentials (ERPs [N100, P300]) were recorded. In all participants, relative to the control condition, probe N100 was enhanced to both predictable and unpredictable threat, whereas P300 suppression was unique to predictable threat. Probe N100, but not P300, was associated with startle eyeblink during both threatening conditions, and was strongest for unpredictable threat. PD was not associated with ERPs, but anxiety sensitivity (physical concerns) was positively associated with probe N100 (indicating reduced responding) in the unpredictable condition independent of PD diagnosis. Vulnerability to panic-related psychopathology may be characterized by aberrant early processing of threat, which may be especially evident during anticipation of unpredictable threats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

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    Kuldeep Singh Sachdeva

    Full Text Available In India as elsewhere, multi-drug resistance (MDR poses a serious challenge in the control of tuberculosis (TB. The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST. Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

  10. Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats.

    Science.gov (United States)

    Gatch, Michael B; Dolan, Sean B; Forster, Michael J

    2017-04-01

    Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds. The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogs of cathinone: α-pyrrolidinopropiophenone (α-PPP), α-pyrrolidinohexiophenone (α-PHP), α-pyrrolidinopentiothiophenone (α-PVT), 3,4-methylenedioxybutiophenone (MDPBP), and ethylone. Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle. Each of the compounds produced an inverted-U dose-effect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP > α-PPP = α-PHP > ethylone > α-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. α-PPP, α-PHP, and ethylone fully substituted for cocaine. α-PVT produced a maximum of 50% cocaine-appropriate responding, and MDPBP produced an inverted-U-shaped dose-effect curve with maximum effects of 67%. These data provide initial evidence that these structurally similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.

  11. Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats.

    Science.gov (United States)

    Souza, Leonardo C; Martynhak, Bruno J; Bassani, Taysa B; Turnes, Joelle de M; Machado, Meira M; Moura, Eric; Andreatini, Roberto; Vital, Maria A B F

    2018-05-01

    Parkinson's disease (PD) patients often suffer from circadian locomotor rhythms impairment and depression, important non-motor symptoms. It is known that toxin-based animal models of PD can reproduce these features. In a 6-hydroxydopamine (6-OHDA) intranigral model, we first investigated the possible disturbances on circadian rhythms of locomotor activity. The rats were divided into 6-OHDA and Sham groups. After a partial dopaminergic lesion, the 6-OHDA group showed slight alterations in different circadian locomotor rhythms parameters. In a second experiment, we hypothesized agomelatine, an melatoninergic antidepressant with potential to resynchronize disturbed rhythms, could prevent neuronal damage and rhythm alterations in the same 6-OHDA model. The animals were divided into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. However, the treated animals (agomelatine 50 mg/kg for 22 days) showed an impaired rhythm robustness, and agomelatine did not induce significant changes in the other circadian parameters nor neuroprotection. Finally, in a third experiment, we examined the effects of agomelatine in the 6-OHDA model regarding depressive-like behavior, evaluated by sucrose preference test. The animals were also divided into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. The toxin infused animals showed a decrease in sucrose preference in comparison with the vehicle infused animals, however, agomelatine did not prevent this decrease. Our findings indicate that agomelatine worsened circadian locomotor rhythm and was not able to reverse the depressive-like behavior of rats in the 6-OHDA PD model. Copyright © 2018. Published by Elsevier Inc.

  12. Locomotor Behavior of Chickens Anticipating Incline Walking

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    Chantal LeBlanc

    2018-01-01

    Full Text Available Keel bone damage (KBD is prevalent in hens raised for egg production, and ramps between different tiers in aviaries have potential to reduce the frequency of falls resulting in KBD. Effective use of ramps requires modulation of locomotion in anticipation of the incline. Inadequate adaptive locomotion may be one explanation why domestic layer hens (Gallus gallus domesticus exhibit high rates of KBD. To improve understanding of the capacity of hens to modulate their locomotion in anticipation of climbing, we measured the effects of incline angle upon the mechanics of the preparatory step before ascending a ramp. Because the energetic challenge of climbing increases with slope, we predicted that as angle of incline increased, birds during foot contact with the ground before starting to climb would increase their peak force and duration of contact and reduce variation in center of pressure (COP under their foot. We tested 20 female domestic chickens on ramp inclines at slopes of +0°, +40°, and +70° when birds were 17, 21, 26, 31, and 36 weeks of age. There were significantly higher vertical peak ground reaction forces in preparation at the steepest slope, and ground contact time increased significantly with each increase in ramp angle. Effects upon variation in COP were not apparent; likewise, effects of limb length, age, body mass were not significant. Our results reveal that domestic chickens are capable of modulating their locomotion in response to incline angle.

  13. An Integrated Gait and Balance Analysis System to Define Human Locomotor Control

    Science.gov (United States)

    2016-04-29

    test hypotheses they developed about how people walk. An Integrated Gait and Balance Analysis System to define Human Locomotor Control W911NF-14-R-0009...An Integrated Gait and Balance Analysis System to Define Human Locomotor Control Walking is a complicated task that requires the motor coordination...Gait and Balance Analysis System to Define Human Locomotor Control Report Title Walking is a complicated task that requires the motor coordination across

  14. Locomotor activity: A distinctive index in morphine self-administration in rats

    Science.gov (United States)

    Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration. PMID:28380023

  15. Locomotor activity: A distinctive index in morphine self-administration in rats.

    Science.gov (United States)

    Zhang, Jian-Jun; Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration.

  16. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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    A. Zago

    2012-01-01

    Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  17. Sensitivity of cortical auditory evoked potential detection for hearing-impaired infants in response to short speech sounds

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    Bram Van Dun

    2012-01-01

    Full Text Available

    Background: Cortical auditory evoked potentials (CAEPs are an emerging tool for hearing aid fitting evaluation in young children who cannot provide reliable behavioral feedback. It is therefore useful to determine the relationship between the sensation level of speech sounds and the detection sensitivity of CAEPs.

    Design and methods: Twenty-five sensorineurally hearing impaired infants with an age range of 8 to 30 months were tested once, 18 aided and 7 unaided. First, behavioral thresholds of speech stimuli /m/, /g/, and /t/ were determined using visual reinforcement orientation audiometry (VROA. Afterwards, the same speech stimuli were presented at 55, 65, and 75 dB SPL, and CAEP recordings were made. An automatic statistical detection paradigm was used for CAEP detection.

    Results: For sensation levels above 0, 10, and 20 dB respectively, detection sensitivities were equal to 72 ± 10, 75 ± 10, and 78 ± 12%. In 79% of the cases, automatic detection p-values became smaller when the sensation level was increased by 10 dB.

    Conclusions: The results of this study suggest that the presence or absence of CAEPs can provide some indication of the audibility of a speech sound for infants with sensorineural hearing loss. The detection of a CAEP provides confidence, to a degree commensurate with the detection probability, that the infant is detecting that sound at the level presented. When testing infants where the audibility of speech sounds has not been established behaviorally, the lack of a cortical response indicates the possibility, but by no means a certainty, that the sensation level is 10 dB or less.

  18. Evolution of vertebrate transient receptor potential vanilloid 3 channels: opposite temperature sensitivity between mammals and western clawed frogs.

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    Shigeru Saito

    2011-04-01

    Full Text Available Transient Receptor Potential (TRP channels serve as temperature receptors in a wide variety of animals and must have played crucial roles in thermal adaptation. The TRP vanilloid (TRPV subfamily contains several temperature receptors with different temperature sensitivities. The TRPV3 channel is known to be highly expressed in skin, where it is activated by warm temperatures and serves as a sensor to detect ambient temperatures near the body temperature of homeothermic animals such as mammals. Here we performed comprehensive comparative analyses of the TRPV subfamily in order to understand the evolutionary process; we identified novel TRPV genes and also characterized the evolutionary flexibility of TRPV3 during vertebrate evolution. We cloned the TRPV3 channel from the western clawed frog Xenopus tropicalis to understand the functional evolution of the TRPV3 channel. The amino acid sequences of the N- and C-terminal regions of the TRPV3 channel were highly diversified from those of other terrestrial vertebrate TRPV3 channels, although central portions were well conserved. In a heterologous expression system, several mammalian TRPV3 agonists did not activate the TRPV3 channel of the western clawed frog. Moreover, the frog TRPV3 channel did not respond to heat stimuli, instead it was activated by cold temperatures. Temperature thresholds for activation were about 16 °C, slightly below the lower temperature limit for the western clawed frog. Given that the TRPV3 channel is expressed in skin, its likely role is to detect noxious cold temperatures. Thus, the western clawed frog and mammals acquired opposite temperature sensitivity of the TRPV3 channel in order to detect environmental temperatures suitable for their respective species, indicating that temperature receptors can dynamically change properties to adapt to different thermal environments during evolution.

  19. Biopolymer electrolytes based on blend of kappa-carrageenan and cellulose derivatives for potential application in dye sensitized solar cell

    International Nuclear Information System (INIS)

    Rudhziah, S.; Ahmad, A.; Ahmad, I.; Mohamed, N.S.

    2015-01-01

    system has potential to be applied in dye sensitized solar cell

  20. A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera.

    Science.gov (United States)

    Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

    2015-01-01

    The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee's locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48 h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case of

  1. A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Mercédès Charreton

    Full Text Available The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee's locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…, before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence since (i few studies are available on locomotion at this stage and (ii in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48 h, three pyrethroids, namely cypermethrin (2.5 ng/bee, tetramethrin (70 ng/bee, tau-fluvalinate (33 ng/bee and the neonicotinoid thiamethoxam (3.8 ng/bee caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field

  2. Sound stabilizes locomotor-respiratory coupling and reduces energy cost.

    Directory of Open Access Journals (Sweden)

    Charles P Hoffmann

    Full Text Available A natural synchronization between locomotor and respiratory systems is known to exist for various species and various forms of locomotion. This Locomotor-Respiratory Coupling (LRC is fundamental for the energy transfer between the two subsystems during long duration exercise and originates from mechanical and neurological interactions. Different methodologies have been used to compute LRC, giving rise to various and often diverging results in terms of synchronization, (de-stabilization via information, and associated energy cost. In this article, the theory of nonlinear-coupled oscillators was adopted to characterize LRC, through the model of the sine circle map, and tested it in the context of cycling. Our specific focus was the sound-induced stabilization of LRC and its associated change in energy consumption. In our experimental study, participants were instructed during a cycling exercise to synchronize either their respiration or their pedaling rate with an external auditory stimulus whose rhythm corresponded to their individual preferential breathing or cycling frequencies. Results showed a significant reduction in energy expenditure with auditory stimulation, accompanied by a stabilization of LRC. The sound-induced effect was asymmetrical, with a better stabilizing influence of the metronome on the locomotor system than on the respiratory system. A modification of the respiratory frequency was indeed observed when participants cycled in synchrony with the tone, leading to a transition toward more stable frequency ratios as predicted by the sine circle map. In addition to the classical mechanical and neurological origins of LRC, here we demonstrated using the sine circle map model that information plays an important modulatory role of the synchronization, and has global energetic consequences.

  3. Locomotor skills and balance strategies in adolescents idiopathic scoliosis.

    Science.gov (United States)

    Mallau, Sophie; Bollini, Gérard; Jouve, Jean-Luc; Assaiante, Christine

    2007-01-01

    Locomotor balance control assessment was performed to study the effect of idiopathic scoliosis on head-trunk coordination in 17 patients with adolescent idiopathic scoliosis (AIS) and 16 control subjects. The aim of this study was to explore the functional effects of structural spinal deformations like idiopathic scoliosis on the balance strategies used during locomotion. Up to now, the repercussion of the idiopathic scoliosis on head-trunk coordination and balance strategies during locomotion is relatively unknown. Seventeen patients with AIS (mean age 14 years 3 months, 10 degrees 30 degrees) and 16 control subjects (mean age 14 years 1 month) were tested during various locomotor tasks: walking on the ground, walking on a line, and walking on a beam. Balance control was examined in terms of rotation about the vertical axis (yaw) and on a frontal plane (roll). Kinematics of foot, pelvis, trunk, shoulder, and head rotations were measured with an automatic optical TV image processor in order to calculate angular dispersions and segmental stabilizations. Decreasing the walking speed is the main adaptive strategy used in response to balance problems in control subjects as well as patients with AIS. However, patients with AIS performed walking tasks more slowly than normal subjects (around 15%). Moreover, the pelvic stabilization is preserved, despite the structural changes affecting the spine. Lastly, the biomechanical defect resulting from idiopathic scoliosis mainly affects the yaw head stabilization during locomotion. Patients with AIS show substantial similarities with control subjects in adaptive strategies relative to locomotor velocity as well as balance control based on segmental stabilization. In contrast, the loss of the yaw head stabilization strategies, mainly based on the use of vestibular information, probably reflects the presence of vestibular deficits in the patients with AIS.

  4. Low dose radiation enhances the Locomotor activity of D. melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ki Moon; Lee, Buyng Sub; Nam Seon Young; Kim, Ji Young; Yang, Kwang Hee; Choi, Tae In; Kim, Cha Soon [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Gyeongju (Korea, Republic of)

    2013-04-15

    Mild stresses at low level including radiation can induce the beneficial effects in many vertebrate and invertebrate species. However, a large amount of studies in radiation biology have focused on the detrimental effects of high dose radiation (HDR) such as the increased incidence of cancers and developmental diseases. Low dose radiation (LDR) induces biologically favorable effects in diverse fields, for example, cancer development, genomic instability, immune response, and longevity. Our previous data indicated that LDR promotes cells proliferation of which degree is not much but significant, and microarray data explained that LDR irradiated fruit flies showing the augmented immunity significantly changed the program for gene expression of many genes in Gene Ontology (GO) categories related to metabolic process. Metabolic process in development one of major contributors in organism growth, interbreeding, motility, and aging. Therefore, it is valuable to examine whether LDR change the physiological parameters related to metabolism, and how LDR regulates the metabolism in D. melanogaster. In this study, to investigate that LDR influences change of the metabolism, a representative parameter, locomotor activity. In addition, the activation of several cellular signal molecules was determined to investigate the specific molecular mechanism of LDR effects on the metabolism. We explored whether ionizing radiation affects the motility activity. We performed the RING assays to evaluate the locomotor activity, a representative parameter presenting motility of fruit flies. HDR dramatically decreased the motor activity of irradiated flies. Surprisingly, the irradiated flies at low dose radiation in both acute and chronic showed the significantly increased locomotor activity, compared to non-irradiated flies. Irradiation would induce change of the several signal pathways for flies to respond to it. The activation of some proteins involved in the cells proliferation and stress

  5. Effects of pregnancy on body temperature and locomotor performance of velvet geckos.

    Science.gov (United States)

    Dayananda, Buddhi; Ibargüengoytía, Nora; Whiting, Martin J; Webb, Jonathan K

    2017-04-01

    Pregnancy is a challenging period for egg laying squamates. Carrying eggs can encumber females and decrease their locomotor performance, potentially increasing their risk of predation. Pregnant females can potentially reduce this handicap by selecting higher temperatures to increase their sprint speed and ability to escape from predators, or to speed up embryonic development and reduce the period during which they are burdened with eggs ('selfish mother' hypothesis). Alternatively, females might select more stable body temperatures during pregnancy to enhance offspring fitness ('maternal manipulation hypothesis'), even if the maintenance of such temperatures compromises a female's locomotor performance. We investigated whether pregnancy affects the preferred body temperatures and locomotor performance of female velvet geckos Amalosia lesueurii. We measured running speed of females during late pregnancy, and one week after they laid eggs at four temperatures (20°, 25°, 30° and 35°C). Preferred body temperatures of females were measured in a cost-free thermal gradient during late pregnancy and one week after egg-laying. Females selected higher and more stable set-point temperatures when they were pregnant (mean =29.0°C, T set =27.8-30.5°C) than when they were non-pregnant (mean =26.2°C, T set =23.7-28.7°C). Pregnancy was also associated with impaired performance; females sprinted more slowly at all four test temperatures when burdened with eggs. Although females selected higher body temperatures during late pregnancy, this increase in temperature did not compensate for their impaired running performance. Hence, our results suggest that females select higher temperatures during pregnancy to speed up embryogenesis and reduce the period during which they have reduced performance. This strategy may decrease a female's probability of encountering predatory snakes that use the same microhabitats for thermoregulation. Selection of stable temperatures by pregnant

  6. Sex differences in locomotor effects of morphine in the rat

    OpenAIRE

    Craft, Rebecca M.; Clark, James L.; Hart, Stephen P.; Pinckney, Megan K.

    2006-01-01

    Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into ...

  7. Predictive Measures of Locomotor Performance on an Unstable Walking Surface

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Caldwell, E. E.; Batson, C. D.; De Dios, Y. E.; Gadd, N. E.; Goel, R.; Wood, S. J.; Cohen, H. S.; hide

    2016-01-01

    Locomotion requires integration of visual, vestibular, and somatosensory information to produce the appropriate motor output to control movement. The degree to which these sensory inputs are weighted and reorganized in discordant sensory environments varies by individual and may be predictive of the ability to adapt to novel environments. The goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to inform the design of training countermeasures designed to enhance the ability of astronauts to adapt to gravitational transitions improving balance and locomotor performance after a Mars landing and enhancing egress capability after a landing on Earth.

  8. Designing Functional Clothes for Persons with Locomotor Disabilities

    Directory of Open Access Journals (Sweden)

    Curteza Antonela

    2014-12-01

    Full Text Available The life quality improvement issue is a problem of national and international interest. This acquires total different values when it is to refer to a series of disadvantaged categories, that is the persons with locomotor disabilities. It is an inevitable social responsibility to create equal opportunities for disabled people, to prevent any intentional or unintentional discrimination that they face and apply positive discrimination if necessary to improve their living standards and to let them have an equal share from social development as productive individuals of society.

  9. Three-axis optical force plate for studies in small animal locomotor mechanics

    International Nuclear Information System (INIS)

    Hsieh, S. Tonia

    2006-01-01

    The use of force plates to measure whole-body locomotor mechanics is a well-established technique. However, commercially available force plates are not sensitive enough for use on small-bodied vertebrates or invertebrates. The standard design for single- and multiple-axis, high-sensitivity force plates built by individual research groups uses semiconductor foil strain gauges to measure deflections; yet foil strain gauges are highly temperature and position sensitive, resulting in a drifting base line and nonlinear responses. I present here a design for a three-axis optical force plate that was successfully calibrated to measure forces as small as 1.5 mN and is capable of determining the position of center of pressure with a mean error of 0.07 cm along the X axis and 0.13 cm along the Y axis. Using optical sensors instead of foil strain gauges to measure deflection, this force plate is not subject to temperature-related drift and is more robust against slight positioning inaccuracies. This force plate was used to measure forces produced by amphibious fishes weighing less than 2 g as they jumped off the force platform

  10. Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

    Science.gov (United States)

    Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

    2014-03-01

    The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P alkylating agents.

  11. Sensitivity of potential evapotranspiration estimation to the Thornthwaite and Penman-Monteith methods in the study of global drylands

    Science.gov (United States)

    Yang, Qing; Ma, Zhuguo; Zheng, Ziyan; Duan, Yawen

    2017-12-01

    Drylands are among those regions most sensitive to climate and environmental changes and human-induced perturbations. The most widely accepted definition of the term dryland is a ratio, called the Surface Wetness Index (SWI), of annual precipitation to potential evapotranspiration (PET) being below 0.65. PET is commonly estimated using the Thornthwaite (PET Th) and Penman-Monteith equations (PET PM). The present study compared spatiotemporal characteristics of global drylands based on the SWI with PET Th and PET PM. Results showed vast differences between PET Th and PET PM; however, the SWI derived from the two kinds of PET showed broadly similar characteristics in the interdecadal variability of global and continental drylands, except in North America, with high correlation coefficients ranging from 0.58 to 0.89. It was found that, during 1901-2014, global hyper-arid and semi-arid regions expanded, arid and dry sub-humid regions contracted, and drylands underwent interdecadal fluctuation. This was because precipitation variations made major contributions, whereas PET changes contributed to a much lesser degree. However, distinct differences in the interdecadal variability of semi-arid and dry sub-humid regions were found. This indicated that the influence of PET changes was comparable to that of precipitation variations in the global dry-wet transition zone. Additionally, the contribution of PET changes to the variations in global and continental drylands gradually enhanced with global warming, and the Thornthwaite method was found to be increasingly less applicable under climate change.

  12. CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

    Science.gov (United States)

    Kostal, Jakub; Voutchkova-Kostal, Adelina

    2016-01-19

    Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

  13. Digestive and locomotor capacity show opposing responses to changing food availability in an ambush predatory fish.

    Science.gov (United States)

    Fu, Shi-Jian; Peng, Jing; Killen, Shaun S

    2018-06-14

    Metabolic rates vary widely within species, but little is known about how variation in the 'floor' [i.e. standard metabolic rate (SMR) in ectotherms] and 'ceiling' [maximum metabolic rate (MMR)] for an individual's aerobic scope (AS) are linked with digestive and locomotor function. Any links among metabolic traits and aspects of physiological performance may also be modulated by fluctuations in food availability. This study followed changes in SMR, MMR, and digestive and locomotor capacity in southern catfish ( Silurus meridionalis ) throughout 15 days of food deprivation and 15 days of refeeding. Individuals downregulated SMR during food deprivation and showed only a 10% body mass decrease during this time. Whereas critical swim speed ( U crit ) was robust to food deprivation, digestive function decreased after fasting with a reduced peak oxygen uptake during specific dynamic action (SDA) and prolonged SDA duration. During refeeding, individuals displayed rapid growth and digestive function recovered to pre-fasting levels. However, refed fish showed a lower U crit than would be expected for their increased body length and in comparison to measures at the start of the study. Reduced swimming ability may be a consequence of compensatory growth: growth rate was negatively correlated with changes in U crit during refeeding. Southern catfish downregulate digestive function to reduce energy expenditure during food deprivation, but regain digestive capacity during refeeding, potentially at the cost of decreased swimming performance. The plasticity of maintenance requirements suggests that SMR is a key fitness trait for in this ambush predator. Shifts in trait correlations with food availability suggest that the potential for correlated selection may depend on context. © 2018. Published by The Company of Biologists Ltd.

  14. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Directory of Open Access Journals (Sweden)

    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  15. Optimizing learning of a locomotor task: amplifying errors as needed.

    Science.gov (United States)

    Marchal-Crespo, Laura; López-Olóriz, Jorge; Jaeger, Lukas; Riener, Robert

    2014-01-01

    Research on motor learning has emphasized that errors drive motor adaptation. Thereby, several researchers have proposed robotic training strategies that amplify movement errors rather than decrease them. In this study, the effect of different robotic training strategies that amplify errors on learning a complex locomotor task was investigated. The experiment was conducted with a one degree-of freedom robotic stepper (MARCOS). Subjects were requested to actively coordinate their legs in a desired gait-like pattern in order to track a Lissajous figure presented on a visual display. Learning with three different training strategies was evaluated: (i) No perturbation: the robot follows the subjects' movement without applying any perturbation, (ii) Error amplification: existing errors were amplified with repulsive forces proportional to errors, (iii) Noise disturbance: errors were evoked with a randomly-varying force disturbance. Results showed that training without perturbations was especially suitable for a subset of initially less-skilled subjects, while error amplification seemed to benefit more skilled subjects. Training with error amplification, however, limited transfer of learning. Random disturbing forces benefited learning and promoted transfer in all subjects, probably because it increased attention. These results suggest that learning a locomotor task can be optimized when errors are randomly evoked or amplified based on subjects' initial skill level.

  16. Continuous monitoring of back wall stress corrosion cracking growth in sensitized type 304 stainless steel weldment by means of potential drop techniques

    OpenAIRE

    SATO, Y; ATSUMI, T; SHOJI, T

    2007-01-01

    Stress corrosion cracking (SCC) tests on welded specimens of sensitized type 304SS with a thickness of 20 mm were performed in sodium thiosulphate solution at room temperature, with continuous monitoring of the SCC growth, using the techniques of modified induced current potential drop (MICPD), alternating current potential drop (ACPD) and direct current potential drop (DCPD). The MICPD and DCPD techniques permit continuous monitoring of the back wall SCC, which initiates from a fatigue pre-c...

  17. Runners maintain locomotor-respiratory coupling following isocapnic voluntary hyperpnea to task failure.

    Science.gov (United States)

    Stickford, Abigail S L; Stickford, Jonathon L; Tanner, David A; Stager, Joel M; Chapman, Robert F

    2015-11-01

    Evidence has long suggested that mammalian ventilatory and locomotor rhythms are linked, yet determinants and implications of locomotor-respiratory coupling (LRC) continue to be investigated. Anecdotally, respiratory muscle fatigue seen at the end of heavy exercise may result in an uncoupling of movement-ventilation rhythms; however, there is no scientific evidence to substantiate this claim. We sought to determine whether or not fatigue of the respiratory muscles alters locomotor-respiratory coupling patterns typically observed in highly trained individuals while running. A related query was to examine the relationship between the potential changes in LRC and measures of running economy. Twelve male distance runners ran at four submaximal workloads (68-89 % VO2peak) on two separate days while LRC was quantified. One LRC trial served as a control (CON), while the other was performed following an isocapnic voluntary hyperpnea to task failure to induce respiratory muscle fatigue (FT+). LRC was assessed as stride-to-breathing frequency ratios (SF/fB) and degree of LRC (percentage of breaths occurring during the same decile of the step cycle). Hyperpnea resulted in significant declines in maximal voluntary inspiratory (MIP) and expiratory (MEP) mouth pressures (ΔMIP = -10 ± 12 cm H2O; ΔMEP = -6 ± 9 cm H2O). There were no differences in minute ventilation between CON and FT+ (CON, all speeds pooled = 104 ± 25 L min(-1); FT+ pooled = 106 ± 23 L min(-1)). Stride frequency was not different between trials; however, breathing frequency was significantly greater during FT+ compared to CON at all speeds (CON pooled = 47 ± 10 br min(-1); FT+ pooled = 52 ± 9 br min(-1)), resulting in smaller corresponding SF/fB. Yet, the degree of LRC was the same during CON and FT+ (CON pooled = 63 ± 15 %; FT+ pooled = 64 ± 18 %). The results indicate that trained runners are able to continue entraining breath and step cycles, despite marked changes in exercise breathing frequency

  18. Locomotor problems among rural elderly population in a District of Aligarh, North India.

    Science.gov (United States)

    Maroof, Mohd; Ahmad, Anees; Khalique, Najam; Ansari, M Athar

    2017-01-01

    Locomotor functions decline with the age along with other physiological changes. This results in deterioration of the quality of life with decreased social and economic role in the society, as well as increased dependency, for the health care and other basic services. The demographic transition resulting in increased proportion of elderly may pose a burden to the health system. To find the prevalence of locomotor problems among the elderly population, and related sociodemographic factors. The study was a community-based cross-sectional study done at field practice area of Rural Health Training Centre, JN Medical College, AMU, Aligarh, Uttar Pradesh, India. A sample of 225 was drawn from 1018 elderly population aged 60 years and above using systematic random sampling with probability proportionate to size. Sociodemographic characteristics were obtained using pretested and predesigned questionnaire. Locomotor problems were assessed using the criteria used by National Sample Survey Organization. Data were analyzed using SPSS version 20. Chi-square test was used to test relationship of locomotor problems with sociodemographic factors. P locomotor problems among the elderly population was 25.8%. Locomotor problems were significantly associated with age, gender, and working status whereas no significant association with literacy status and marital status was observed. The study concluded that approximately one-fourth of the elderly population suffered from locomotor problems. The sociodemographic factors related to locomotor problems needs to be addressed properly to help them lead an independent and economically productive life.

  19. Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise

    NARCIS (Netherlands)

    Gispen, W.H.; Meeteren, N.L. van; Eggers, L.; Lankhorst, A.J.; Hamers, F.P.

    2003-01-01

    We have recently shown that enriched environment (EE) housing significantly enhances locomotor recovery following spinal cord contusion injury (SCI) in rats. As the type and intensity of locomotor training with EE housing are rather poorly characterized, we decided to compare the effectiveness of EE

  20. Locomotor Tests Predict Community Mobility in Children and Youth with Cerebral Palsy

    Science.gov (United States)

    Ferland, Chantale; Moffet, Helene; Maltais, Desiree

    2012-01-01

    Ambulatory children and youth with cerebral palsy have limitations in locomotor capacities and in community mobility. The ability of three locomotor tests to predict community mobility in this population (N = 49, 27 boys, 6-16 years old) was examined. The tests were a level ground walking test, the 6-min-Walk-Test (6MWT), and two tests of advanced…

  1. Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern.

    Science.gov (United States)

    Barrière, Grégory; Frigon, Alain; Leblond, Hugues; Provencher, Janyne; Rossignol, Serge

    2010-08-01

    The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.

  2. Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D2 receptor mechanisms.

    Science.gov (United States)

    van de Wetering, Ross; Schenk, Susan

    2017-04-01

    Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown. This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D 2 receptor mechanisms. Rats received the selective D 2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined. Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration. These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D 2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D 2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.

  3. V3 spinal neurons establish a robust and balanced locomotor rhythm during walking.

    Science.gov (United States)

    Zhang, Ying; Narayan, Sujatha; Geiman, Eric; Lanuza, Guillermo M; Velasquez, Tomoko; Shanks, Bayle; Akay, Turgay; Dyck, Jason; Pearson, Keir; Gosgnach, Simon; Fan, Chen-Ming; Goulding, Martyn

    2008-10-09

    A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.

  4. Zeta-potential data reliability of gold nanoparticle biomolecular conjugates and its application in sensitive quantification of surface absorbed protein.

    Science.gov (United States)

    Wang, Wenjie; Ding, Xiaofan; Xu, Qing; Wang, Jing; Wang, Lei; Lou, Xinhui

    2016-12-01

    Zeta potentials (ZP) of gold nanoparticle bioconjugates (AuNP-bios) provide important information on surface charge that is critical for many applications including drug delivery, biosensing, and cell imaging. The ZP measurements (ZPMs) are conducted under an alternative electrical field at a high frequency under laser irradiation, which may strongly affect the status of surface coating of AuNP-bios and generate unreliable data. In this study, we systemically evaluated the ZP data reliability (ZPDR) of citrate-, thiolated single stranded DNA-, and protein-coated AuNPs mainly according to the consistence of ZPs in the repeated ZPMs and the changes of the hydrodynamic size before and after the ZPMs. We found that the ZPDR was highly dependent on both buffer conditions and surface modifications. Overall, the higher ionic strength of the buffer and the lower affinity of surface bounders were related with the worse ZPDR. The ZPDR of citrate-coated AuNP was good in water, but bad in 10mM phosphate buffer (PB), showing substantially decrease of the absolute ZP values after each measurement, probably due to the electrical field facilitated adsorption of negatively charged phosphate ions on AuNPs. The significant desorption of DNAs from AuNP was observed in the PB containing medium concentration of NaCl, but not in PB. The excellent ZPDR of bovine serum albumin (BSA)-coated AuNP was observed at high salt concentrations and low surface coverage, enabling ZPM as an ultra-sensitive tool for protein quantification on the surface of AuNPs with a single molecule resolution. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

    Directory of Open Access Journals (Sweden)

    Bhattacharjee Rakesh

    2010-02-01

    Full Text Available Abstract Introduction Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity. Methods A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65 and non-obese (NOB. Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135, corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped. Results Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values. Conclusions Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.

  6. Visual and kinesthetic locomotor imagery training integrated with auditory step rhythm for walking performance of patients with chronic stroke.

    Science.gov (United States)

    Kim, Jin-Seop; Oh, Duck-Won; Kim, Suhn-Yeop; Choi, Jong-Duk

    2011-02-01

    To compare the effect of visual and kinesthetic locomotor imagery training on walking performance and to determine the clinical feasibility of incorporating auditory step rhythm into the training. Randomized crossover trial. Laboratory of a Department of Physical Therapy. Fifteen subjects with post-stroke hemiparesis. Four locomotor imagery trainings on walking performance: visual locomotor imagery training, kinesthetic locomotor imagery training, visual locomotor imagery training with auditory step rhythm and kinesthetic locomotor imagery training with auditory step rhythm. The timed up-and-go test and electromyographic and kinematic analyses of the affected lower limb during one gait cycle. After the interventions, significant differences were found in the timed up-and-go test results between the visual locomotor imagery training (25.69 ± 16.16 to 23.97 ± 14.30) and the kinesthetic locomotor imagery training with auditory step rhythm (22.68 ± 12.35 to 15.77 ± 8.58) (P kinesthetic locomotor imagery training exhibited significantly increased activation in a greater number of muscles and increased angular displacement of the knee and ankle joints compared with the visual locomotor imagery training, and these effects were more prominent when auditory step rhythm was integrated into each form of locomotor imagery training. The activation of the hamstring during the swing phase and the gastrocnemius during the stance phase, as well as kinematic data of the knee joint, were significantly different for posttest values between the visual locomotor imagery training and the kinesthetic locomotor imagery training with auditory step rhythm (P kinesthetic locomotor imagery training than in the visual locomotor imagery training. The auditory step rhythm together with the locomotor imagery training produces a greater positive effect in improving the walking performance of patients with post-stroke hemiparesis.

  7. Acetylcholinesterase inhibition and locomotor function after motor-sensory cortex impact injury.

    Science.gov (United States)

    Holschneider, Daniel P; Guo, Yumei; Roch, Margareth; Norman, Keith M; Scremin, Oscar U

    2011-09-01

    Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 μmol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 μmol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses.

  8. Training Enhances Both Locomotor and Cognitive Adaptability to a Novel Sensory Environment

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Ploutz-Snyder, R. J.; Cohen, H. S.

    2010-01-01

    During adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform required mission tasks. The goal of this project is to develop a sensorimotor adaptability (SA) training program to facilitate rapid adaptation. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene that provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. The goal of our present study was to determine if SA training improved both the locomotor and cognitive responses to a novel sensory environment and to quantify the extent to which training would be retained. Methods: Twenty subjects (10 training, 10 control) completed three, 30-minute training sessions during which they walked on the treadmill while receiving discordant support surface and visual input. Control subjects walked on the treadmill but did not receive any support surface or visual alterations. To determine the efficacy of training all subjects performed the Transfer Test upon completion of training. For this test, subjects were exposed to novel visual flow and support surface movement, not previously experienced during training. The Transfer Test was performed 20 minutes, 1 week, 1, 3 and 6 months after the final training session. Stride frequency, auditory reaction time, and heart rate data were collected as measures of postural stability, cognitive effort and anxiety, respectively. Results: Using mixed effects regression methods we determined that subjects who received SA training showed less alterations in stride frequency, auditory reaction time and heart rate compared to controls. Conclusion: Subjects who received SA training improved performance across a number of modalities including enhanced locomotor function, increased multi-tasking capability and reduced anxiety during adaptation to novel discordant sensory

  9. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    International Nuclear Information System (INIS)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

    2012-01-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  10. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  11. Locomotor circumvention strategies are altered by stroke: I. Obstacle clearance.

    Science.gov (United States)

    Darekar, Anuja; Lamontagne, Anouk; Fung, Joyce

    2017-06-15

    Functional locomotion requires the ability to adapt to environmental challenges such as the presence of stationary or moving obstacles. Difficulties in obstacle circumvention often lead to restricted community ambulation in individuals with stroke. The objective of this study was to contrast obstacle circumvention strategies between post-stroke (n = 12) and healthy individuals (n = 12) performing locomotor and perceptuomotor (joystick navigation) tasks with different obstacle approaches. Participants walked and navigated with a joystick towards a central target, in a virtual environment simulating a large room, while avoiding an obstacle that either remained stationary at the pre-determined point of intersection or moved from head-on or diagonally 30° left/right. The outcome measures included dynamic clearance (DC), instantaneous distance from obstacle at crossing (IDC), number of collisions and preferred side of circumvention. These measures were compared between groups (stroke vs. healthy), obstacle parameter (stationary vs. moving head-on) and direction of approach (left/paretic vs. right/non-paretic). DC was significantly larger when circumventing a moving obstacle that approached head-on as compared to a stationary obstacle for both groups during both tasks, while not significantly different in either diagonal approach in either group. IDC was smaller in the stroke group while walking and larger in both groups during joystick navigation when avoiding moving as compared to stationary obstacle. IDC was significantly larger in the stroke group compared to controls for diagonal approaches during walking, wherein two different strategies emerged amongst individuals with stroke: circumventing to the same (V same n = 6) or opposite (V opp n = 4) side of obstacle approach. This behavior was not seen in the perceptuomotor task, wherein post-stroke participants circumvented to opposite side of the obstacle approach as seen in healthy participants. In the

  12. Control of locomotor stability in stabilizing and destabilizing environments.

    Science.gov (United States)

    Wu, Mengnan/Mary; Brown, Geoffrey; Gordon, Keith E

    2017-06-01

    To develop effective interventions targeting locomotor stability, it is crucial to understand how people control and modify gait in response to changes in stabilization requirements. Our purpose was to examine how individuals with and without incomplete spinal cord injury (iSCI) control lateral stability in haptic walking environments that increase or decrease stabilization demands. We hypothesized that people would adapt to walking in a predictable, stabilizing viscous force field and unpredictable destabilizing force field by increasing and decreasing feedforward control of lateral stability, respectively. Adaptations in feedforward control were measured using after-effects when fields were removed. Both groups significantly (pfeedforward adaptions to increase control of lateral stability. In contrast, in the destabilizing field, non-impaired subjects increased movement variability (p0.05). When the destabilizing field was removed, increases in movement variability persisted (pfeedforward decreases in resistance to perturbations. Published by Elsevier B.V.

  13. A Multiposture Locomotor Training Device with Force-Field Control

    Directory of Open Access Journals (Sweden)

    Jianfeng Sui

    2014-11-01

    Full Text Available This paper introduces a multiposture locomotor training device (MPLTD with a closed-loop control scheme based on joint angle feedback, which is able to overcome various difficulties resulting from mechanical vibration and the weight of trainer to achieve higher accuracy trajectory. By introducing the force-field control scheme used in the closed-loop control, the device can obtain the active-constrained mode including the passive one. The MPLTD is mainly composed of three systems: posture adjusting and weight support system, lower limb exoskeleton system, and control system, of which the lower limb exoskeleton system mainly includes the indifferent equilibrium mechanism with two degrees of freedom (DOF and the driving torque is calculated by the Lagrangian function. In addition, a series of experiments, the weight support and the trajectory accuracy experiment, demonstrate a good performance of mechanical structure and the closed-loop control.

  14. Proprioceptive input resets central locomotor rhythm in the spinal cat

    DEFF Research Database (Denmark)

    Conway, B. A.; Hultborn, H.; Kiehn, O.

    1987-01-01

    The reflex regulation of stepping is an important factor in adapting the step cycle to changes in the environment. The present experiments have examined the influence of muscle proprioceptors on centrally generated rhythmic locomotor activity in decerebrate unanesthetized cats with a spinal...... fictive locomotion in a coordinated fashion. An extensor group I volley delivered during a flexor burst would abruptly terminate the flexor activity and initiate an extensor burst. The same stimulus given during an extensor burst prolonged the extensor activity while delaying the appearance...... afferents. Thus an increased load of limb extensors during the stance phase would enhance and prolong extensor activity while simultaneously delaying the transition to the swing phase of the step cycle....

  15. Immature spinal locomotor output in children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Germana Cappellini

    2016-10-01

    Full Text Available Detailed descriptions of gait impairments have been reported in cerebral palsy (CP, but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analysed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years and 33 typically developing (TD children (1-12 years. TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children. Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behaviour.

  16. Enkephalin and dynorphin neuropeptides are differently correlated with locomotor hypersensitivity and levodopa-induced dyskinesia in parkinsonian rats.

    Science.gov (United States)

    Sgroi, Stefania; Capper-Loup, Christine; Paganetti, Paolo; Kaelin-Lang, Alain

    2016-06-01

    The opioidergic neuropeptides dynorphin (DYN) and enkephalin (ENK) and the D1 and D2 dopaminergic receptors (D1R, D2R) are involved in the striatal control of motor and behavioral function. In Parkinson's disease, motor disturbances such as "on-off" motor fluctuations and involuntary movements (dyskinesia) are severe complications that often arise after chronic l-dihydroxyphenylalanine (l-DOPA) treatment. Changes in the striatal expression of preproENK (PPENK), proDYN (PDYN), D1R, and D2R mRNA have been observed in parkinsonian animals treated with l-DOPA. Enhanced opioidergic transmission has been found in association with l-DOPA-induced dyskinesia, but the connection of PPENK, PDYN, D1R, and D2R mRNA expression with locomotor activity remains unclear. In this study, we measured PPENK, PDYN, D1R and D2R mRNA levels by in situ hybridization in the striatum of 6-OHDA hemi-parkinsonian rats treated with l-DOPA (PD+l-DOPA group), along with two control groups (PD+saline and naive+l-DOPA). We found different levels of expression of PPENK, PDYN, D1R and D2R mRNA across the experimental groups and correlated the changes in mRNA expression with dyskinesia and locomotor variables assessed by open field test during several phases of l-DOPA treatment. Both PDYN and PPENK mRNA levels were correlated with the severity of dyskinesia, while PPENK mRNA levels were also correlated with the frequency of contralateral rotational movements and with locomotor variables. Moreover, a strong correlation was found between D1R mRNA expression and D2R mRNA expression in the PD+l-DOPA group. These findings suggest that, in parkinsonian animals treated with l-DOPA, high levels of PPENK are a prerequisite for a locomotor sensitization to l-DOPA treatment, while PDYN overexpression is responsible only for the development of dyskinesia. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Expression of surface markers on the human monocytic leukaemia cell line, THP-1, as indicators for the sensitizing potential of chemicals.

    Science.gov (United States)

    An, Susun; Kim, Seoyoung; Huh, Yong; Lee, Tae Ryong; Kim, Han-Kon; Park, Kui-Lea; Eun, Hee Chul

    2009-04-01

    Evaluation of skin sensitization potential is an important part of the safety assessment of cosmetic ingredients and topical drugs. Recently, evaluation of changes in surface marker expression induced in dendritic cells (DC) or DC surrogate cell lines following exposure to chemicals represents one approach for in vitro test methods. The study aimed to test the change of expression patterns of surface markers on THP-1 cells by chemicals as a predictive in vitro method for contact sensitization. We investigated the expression of CD54, CD86, CD83, CD80, and CD40 after a 1-day exposure to sensitizers (1-chloro-2,4-dinitrobenzene; 2,4-dinitrofluorobenzene; benzocaine; 5-chloro-2-methyl-4-isothiazolin-3-one; hexyl cinnamic aldehyde; eugenol; nickel sulfate hexahydrate; potassium dichromate; cobalt sulfate; 2-mercaptobenzothiazole; and ammonium tetrachloroplatinate) and non-sensitizers (sodium lauryl sulfate, benzalkonium chloride, lactic acid, salicylic acid, isopropanol, and dimethyl sulphoxide). The test concentrations were 0.1x, 0.5x, and 1x of the 50% inhibitory concentration, and the relative fluorescence intensity was used as an expression indicator. By evaluating the expression patterns of CD54, CD86, and CD40, we could classify the chemicals as sensitizers or non-sensitizers, but CD80 and CD83 showed non-specific patterns of expression. These data suggest that the THP-1 cells are good model for screening contact sensitizers and CD40 could be a useful marker complementary to CD54 and CD86.

  18. Sensitividade e especificidade do potencial de média latência Sensitivity and specificity of middle latency potential

    Directory of Open Access Journals (Sweden)

    Eliane Schochat

    2004-06-01

    dysfunction of the central auditory nervous system. The MLR waves occur between 10 and 80 msec (ms after the stimulus onset. The Pa is the most reliable because it is the most visible and robust of this potential. Because of the big variability of the amplitude and the latency of the MLR waves it is not yet largely used in the clinical set. AIM: The purpose of this study was to establish the sensitivity and specificity of the MLR waves. STUDY DESIGN: Case-control. MATERIAL AND METHOD: Individuals between 15 and 55 years old with lesion of the central auditory nervous system, with auditory processing disorders and normal one (control group were evaluated using the MLR. RESULTS: The results showed that the amplitude difference of 30% held the better results, for the electrode as well as the ear effect. The ear effect was more efficient in detecting auditory processing disorder while the electrode effect was better for detecting the lesion.

  19. Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury

    Science.gov (United States)

    Cummings, Brian J.; Engesser-Cesar, Christie; Anderson, Aileen J.

    2007-01-01

    Locomotor impairments after spinal cord injury (SCI) are often assessed using open-field rating scales. These tasks have the advantage of spanning the range from complete paralysis to normal walking; however, they lack sensitivity at specific levels of recovery. Additionally, most supplemental assessments were developed in rats, not mice. For example, the horizontal ladder beam has been used to measure recovery in the rat after SCI. This parametric task results in a videotaped archival record of the event, is easily administered, and is unambiguously scored. Although a ladder beam apparatus for mice is available, its use in the assessment of recovery in SCI mice is rare, possibly because normative data for uninjured mice and the type of step misplacements injured mice exhibit is lacking. We report the development of a modified ladder beam instrument and scoring system to measure hindlimb recovery in vertebral T9 contusion spinal cord injured mice. The mouse ladder beam allows for the use of standard parametric statistical tests to assess locomotor recovery. Ladder beam performance is consistent across four strains of mice, there are no sex differences, and inter-rater reliability between observers is high. The ladder beam score is proportional to injury severity and can be used to easily separate mice capable of weight-supported stance up to mice with consistent forelimb to hindlimb coordination. Critically, horizontal ladder beam testing discriminates between mice that score identically in terms of stepping frequency in open-field testing. PMID:17197044

  20. Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury.

    Science.gov (United States)

    Cummings, Brian J; Engesser-Cesar, Christie; Cadena, Gilbert; Anderson, Aileen J

    2007-02-27

    Locomotor impairments after spinal cord injury (SCI) are often assessed using open-field rating scales. These tasks have the advantage of spanning the range from complete paralysis to normal walking; however, they lack sensitivity at specific levels of recovery. Additionally, most supplemental assessments were developed in rats, not mice. For example, the horizontal ladder beam has been used to measure recovery in the rat after SCI. This parametric task results in a videotaped archival record of the event, is easily administered, and is unambiguously scored. Although a ladder beam apparatus for mice is available, its use in the assessment of recovery in SCI mice is rare, possibly because normative data for uninjured mice and the type of step misplacements injured mice exhibit is lacking. We report the development of a modified ladder beam instrument and scoring system to measure hindlimb recovery in vertebral T9 contusion spinal cord injured mice. The mouse ladder beam allows for the use of standard parametric statistical tests to assess locomotor recovery. Ladder beam performance is consistent across four strains of mice, there are no sex differences, and inter-rater reliability between observers is high. The ladder beam score is proportional to injury severity and can be used to easily separate mice capable of weight-supported stance up to mice with consistent forelimb to hindlimb coordination. Critically, horizontal ladder beam testing discriminates between mice that score identically in terms of stepping frequency in open-field testing.

  1. Rash impulsiveness and reward sensitivity in relation to risky drinking by university students: potential roles of frontal systems.

    Science.gov (United States)

    Lyvers, Michael; Duff, Helen; Basch, Vanessa; Edwards, Mark S

    2012-08-01

    Two forms of impulsivity, rash impulsiveness and reward sensitivity, have been proposed to reflect aspects of frontal lobe functioning and promote substance use. The present study examined these two forms of impulsivity as well as frontal lobe symptoms in relation to risky drinking by university students. University undergraduates aged 18-26years completed the Alcohol Use Disorders Identification Test (AUDIT), Barratt Impulsiveness Scale (BIS-11), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), Frontal Systems Behavior Scale (FrSBe), and a demographics questionnaire assessing age, gender, and age of onset of weekly drinking (AOD). AUDIT-defined harmful drinkers reported earlier AOD and scored higher on BIS-11, the Sensitivity to Reward (SR) scale of the SPSRQ, and the Disinhibition and Executive Dysfunction scales of the FrSBe compared to lower risk groups. Differences remained significant after controlling for duration of alcohol exposure. Path analyses indicated that the influence of SR on AUDIT was mediated by FrSBe Disinhibition, whereas the influence of BIS-11 on AUDIT was mediated by both Disinhibition and Executive Dysfunction scales of the FrSBe. Findings tentatively suggest that the influence of rash impulsiveness on drinking may reflect dysfunction in dorsolateral prefrontal and orbitofrontal systems, whereas the influence of reward sensitivity on drinking may primarily reflect orbitofrontal dysfunction. Irrespective of the underlying functional brain systems involved, results appear to be more consistent with a pre-drinking trait interpretation than effects of alcohol exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Low impedance pH sensitive electrochemical devices that are potentially applicable to transcutaneous PCO2 measurements.

    Science.gov (United States)

    Yeung, H N; Beran, A V; Huxtable, R F

    1978-01-01

    Two cases of low impedance, non-glass membrane electrodes for pH measurement were evaluated: (I) Metal--metal oxide electrodes and (II) Reduction-oxidation electrodes. The fundamental cause of oxygen sensitivity of metal-metal oxide electrodes were examined and three approaches for its suppression were proposed. For the case of Sb--Sb2Ox electordes, oxygen sensitivity can be attenuated partially by cell loading, either directly across the reference electrode or indirectly across a third slave electrode. In a PO2 range of 8--54 kPa, more than 95% of the PO2 response can be suppressed by loading the cell emf to half of tis open-circuit value. The oxygen sensitivity also was observed to diminished by grinding the metal-metal oxide and pressing it under high pressure into a pellet electrode. Other metal-metal oxide electrodes that have promise in transcutaneous measurement are the Pd-PdO2 electrodes. The redox electrodes are typified by the Quinhydrone electrode. A membrane Quinhydrome electrode showed a sensitivity of 56 mV/Decade at 37 degree C and no oxygen sensitivity up to 50 kPa and a drift of 1 mV/h over a 24-h period. However, the stability deteriorated over a long-term period.

  3. Developing the content of a locomotor disability scale for adults in Bangladesh: a qualitative study.

    Science.gov (United States)

    Mahmud, Ilias; Clarke, Lynda; Ploubidis, George B

    2017-01-01

    Bangladesh has an estimated 17 million adults with disabilities. A significant proportion of them are believed to have locomotor disabilities. There are over 300 non-governmental organizations providing different types of rehabilitation services to them. However, there is no locally developed and validated locomotor disability measurement scale in Bangladesh. The purpose of this study was to develop a locomotor disability scale with disability indicators suitable for adults in Bangladesh. Semi-structured interviews were conducted with 25 purposively selected adults with locomotor disabilities to generate scale items. At the second stage, cognitive interviews were conducted with 12 purposively selected adults with locomotor disabilities in order to refine the measurement questions and response categories. Data were analysed using the framework technique- identifying, abstracting, charting and matching themes across the interviews. For a locomotor disability scale, 70 activities (disability indicators) were identified: 37 mobility activities, 9 activities of daily living, 17 work/productivity activities and 7 leisure activities. Cognitive interviews revealed that when asking the respondents to rate their difficulty in performing the activities, instead of just mentioning the activity name, such as taking a bath or shower, a detailed description of the activity and response options were necessary to ensure consistent interpretation of the disability indicators and response options across all respondents. Identifying suitable disability indicators was the first step in developing a locomotor disability scale for adults in Bangladesh. Interviewing adults with locomotor disabilities in Bangladesh ensured that the locomotor disability scale is of relevance to them and consequently it has excellent content validity. Further research is needed to evaluate the psychometric properties of this scale.

  4. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

    International Nuclear Information System (INIS)

    Sebastian, Katrin; Ott, Hagen; Zwadlo-Klarwasser, Gabriele; Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F.; Baron, Jens Malte

    2012-01-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  5. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Sebastian, Katrin, E-mail: ksebastian@ukaachen.de [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Ott, Hagen [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Zwadlo-Klarwasser, Gabriele [IZKF (BIOMAT), RWTH Aachen University Hospital, D-52074 Aachen (Germany); Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F.; Baron, Jens Malte [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  6. A new method for registration of kinesthetic evoked potentials for studies of proprioceptive sensitivity in normal subjects and patients with organic lesions in the brain.

    Science.gov (United States)

    Gordeev, S A; Voronin, S G

    2015-01-01

    The proprioceptive sensitivity of healthy volunteers and convalescents after acute cerebrovascular episodes was studied by a new neurophysiological method for registration of kinesthetic evoked potentials emerging in response to passive 50(o) bending of the hand in the wrist joint with the angular acceleration of 350 rad/sec(2). Kinesthetic evoked potentials were recorded above the somatosensory cortex projection areas in the hemispheres contra- and ipsilateral to the stimulated limb. The patients exhibited significantly longer latencies and lesser amplitudes of the early components of response in the involved hemisphere in comparison with normal subjects. The method for registration of the kinesthetic evoked potentials allows a more detailed study of the mechanisms of kinesthetic sensitivity in health and in organic involvement of the brain.

  7. Transfection mediated by pH-sensitive sugar-based gemini surfactants; potential for in vivo gene therapy applications

    NARCIS (Netherlands)

    Wasungu, Luc; Scarzello, Marco; van Dam, Gooitzen; Molema, Grietje; Wagenaar, Anno; Engberts, Jan B. F. N.; Hoekstra, Dick

    In this study, the in vitro and in vivo transfection capacity of novel pH-sensitive sugar-based gemini surfactants was investigated. In an aqueous environment at physiological pH, these compounds form bilayer vesicles, but they undergo a lamellar-to-micellar phase transition in the endosomal pH

  8. Risk factors associated with sensitive skin and potential role of lifestyle habits: a cross-sectional study

    NARCIS (Netherlands)

    Falcone, D.; Richters, R.J.H.; Uzunbajakava, N.E.; Erp, P.E.J. van; Kerkhof, P.C.M. van de

    2017-01-01

    Sensitive skin (SS) is a widespread condition, but still not completely understood. To identify risk factors that increase the likelihood of SS, 258 women aged between 20 and 65 years old and resident in the Netherlands were surveyed by questionnaire, which included questions on sociodemographic

  9. Development and Utilization of an Ex Vivo Bromodeoxyuridine Local Lymph Node Assay (LLNA) Protocol for Assessing Potential Chemical Sensitizers

    Science.gov (United States)

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

  10. Heat processing of peanut seed enhances the sensitization potential of the major peanut allergen Ara h 6.

    Science.gov (United States)

    Guillon, Blanche; Bernard, Hervé; Drumare, Marie-Françoise; Hazebrouck, Stéphane; Adel-Patient, Karine

    2016-12-01

    Processing of food has been shown to impact IgE binding and functionality of food allergens. In the present study, we investigated the impact of heat processing on the sensitization capacity of Ara h 6, a major peanut allergen and one of the most potent elicitors of the allergic reaction. Peanut extracts obtained from raw or heat-processed peanut and some fractions thereof were biochemically and immunochemically characterized. These extracts/fractions, purified Ara h 6, or recombinant Ara h 6 including Ara h 6 mutants lacking disulfide bridges were used in in vitro digestion tests and mouse models of experimental sensitization. Peanut roasting led to the formation of complexes of high molecular weight, notably between Ara h 6 and Ara h 1, which supported the induction of IgE specific to native Ara h 6. On the contrary, a fraction containing free monomeric 2S albumins or purified native Ara h 6 displayed no intrinsic allergenicity. In addition to complex formation, heat denaturation and/or partial destabilization enhanced Ara h 6 immunogenicity and increased its sensitivity to digestion. These results suggest that sensitization potency and IgE binding capacity can be supported by different structures, modified and/or produced during food processing in interaction with other food constituents. © 2016 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Two different avian cold-sensitive sensory neurons: Transient receptor potential melastatin 8 (TRPM8)-dependent and -independent activation mechanisms.

    Science.gov (United States)

    Yamamoto, A; Takahashi, K; Saito, S; Tominaga, M; Ohta, T

    2016-12-01

    Sensing the ambient temperature is an important function for survival in animals. Some TRP channels play important roles as detectors of temperature and irritating chemicals. There are functional differences of TRP channels among species. TRPM8 in mammals is activated by cooling compounds and cold temperature, but less information is available on the functional role of TRPM8 in avian species. Here we investigated the pharmacological properties and thermal sensitivities of chicken TRPM8 (cTRPM8) and cold-sensitive mechanisms in avian sensory neurons. In heterologously expressed cTRPM8, menthol and its derivative, WS-12 elicited [Ca 2+ ] i increases, but icilin did not. In chicken sensory neurons, icilin increased [Ca 2+ ] i, in a TRPA1-dependent manner. Icilin selectively stimulated heterologously expressed chicken TRPA1 (cTRPA1). Similar to mammalian orthologue, cTRPM8 was activated by cold. Both heterologous and endogenous expressed cTRPM8 were sensitive to mammalian TRPM8 antagonists. There are two types of cold-sensitive cells regarding menthol sensitivity in chicken sensory neurons. The temperature threshold of menthol-insensitive neurons was significantly lower than that of menthol-sensitive ones. The population of menthol-insensitive neurons was large in chicken but almost little in mammals. The cold-induced [Ca 2+ ] i increases were not abolished by the external Ca 2+ removal or by blockades of PLC-IP 3 pathways and ryanodine channels. The cold stimulation failed to evoke [Ca 2+ ] i increases after intracellular Ca 2+ store-depletion. These results indicate that cTRPM8 acts as a cold-sensor similar to mammals. It is noteworthy that TRPM8-independent cold-sensitive neurons are abundant in chicken sensory neurons. Our results suggest that most of the cold-induced [Ca 2+ ] i increases are mediated via Ca 2+ release from intracellular stores and that these mechanisms may be specific to avian species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers.

    Science.gov (United States)

    Williams, W C; Copeland, C; Boykin, E; Quell, S J; Lehmann, D M

    2015-01-01

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [(3) H]methyl thymidine. A more recent non-isotopic variation of the assay utilizes bromodeoxyuridine (BrdU) incorporation in vivo. To further improve the utility of this assay, we developed an ex vivo BrdU labeling procedure eliminating the need for in vivo injections. The results of this assay correctly identified a strong sensitizer (i.e., trimellitic anhydride) as well as weak/moderate sensitizers (i.e., eugenol, cinnamaldehyde and hexylcinnaminic aldehyde). As anticipated, neither non-sensitizers isopropanol and lactic acid nor the false negative chemical nickel II sulfate hexahydrate induced a positive threshold response in the assay. The results of this assay are in close agreement with those of the in vivo LLNA:BrdU-enzyme-linked immunosorbent assay labeling procedure. We also used the ex vivo BrdU LLNA procedure to evaluate ammonium hexachloroplatinate, ammonium tetrachloroplatinate and cis-diamminedichloroplatinum(II) and the assay correctly identified them as sensitizers based on the calculation of EC2 values. We conclude that this ex vivo BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  13. Qualification of spontaneous undirected locomotor behavior of fish for sublethal toxicity testing. Part 2. Variability of measurement parameters under toxicant-induced stress

    Energy Technology Data Exchange (ETDEWEB)

    Grillitsch, B.; Vogl, C.; Wytek, R.

    1999-12-01

    Spontaneous locomotor behavior of semiadult zebra fish (Brachydanio rerio) was recorded under sublethal short-term exposure to the anionic technical surfactant, linear alkylbenzene sulfonate (C{sub 10-13}-LAS) and cadmium in single compound tests using an automated video-monitoring and object-tracing system. Vertical position and swimming velocity in the horizontal and vertical directions were used as behavioral measurement parameters. Data were analyzed by different statistical methods. In pairwise comparisons, consistent, statistically significant, and toxicant-induced alterations of locomotor behavior were observed only for test concentrations, which also caused aspectoric symptoms of intoxication. This comparatively low sensitivity of the behavioral indication criteria was related to high variation in the measurement parameters and corresponding high, minimum detectable, statistically significant, and toxicant-induced deviations. In contrast, results obtained by regression analysis showed significant trends in locomotor activity over the range of toxicant concentrations tested. Thus, the findings support the inappropriateness of no observed effect concentrations and the lowest observed effect concentrations as summary measures of toxicity and indicate that the regression analysis approach is superior to the analysis of variance approach.

  14. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

    International Nuclear Information System (INIS)

    DuRant, Sarah E.; Hopkins, William A.; Talent, Larry G.

    2007-01-01

    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 μg/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards

  15. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

    Energy Technology Data Exchange (ETDEWEB)

    DuRant, Sarah E. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States); University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States); Hopkins, William A. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States) and University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail: hopkinsw@vt.edu; Talent, Larry G. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States)

    2007-09-15

    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 {mu}g/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards.

  16. Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound

    International Nuclear Information System (INIS)

    Galvao dos Santos, G.; Reinders, J.; Ouwehand, K.; Rustemeyer, T.; Scheper, R.J.; Gibbs, S.

    2009-01-01

    Allergic contact dermatitis is the result of an adaptive immune response of the skin to direct exposure to an allergen. Since many chemicals are also allergens, European regulations require strict screening of all ingredients in consumer products. Until recently, identifying a potential allergen has completely relied on animal testing (e.g.: Local Lymph Node Assay). In addition to the ethical problems, both the 7th Amendment to the Cosmetics Directive and REACH have stimulated the development of alternative tests for the assessment of potential sensitizers. This review is aimed at summarising the progress on cell based assays, in particular dendritic cell based assays, being developed as animal alternatives. Primary cells (CD34 + derived dendritic cells, monocyte derived dendritic cells) as well as dendritic cell-like cell lines (THP-1, U-937, MUTZ-3, KG-1, HL-60, and K562) are extensively described along with biomarkers such as cell surface markers, cytokines, chemokines and kinases. From this review, it can be concluded that no single cell based assay nor single marker is yet able to distinguish all sensitizers from non-sensitizers in a test panel of chemicals, nor is it possible to rank the sensitizing potential of the test chemicals. This suggests that sensitivity and specificity may be increased by a tiered assay approach. Only a limited number of genomic and proteomic studies have been completed until now. Such studies have the potential to identify novel biomarkers for inclusion in future assay development. Although progress is promising, this review suggests that it may be difficult to meet the up and coming European regulatory deadlines.

  17. Mouse short- and long-term locomotor activity analyzed by video tracking software.

    Science.gov (United States)

    York, Jason M; Blevins, Neil A; McNeil, Leslie K; Freund, Gregory G

    2013-06-20

    Locomotor activity (LMA) is a simple and easily performed measurement of behavior in mice and other rodents. Improvements in video tracking software (VTS) have allowed it to be coupled to LMA testing, dramatically improving specificity and sensitivity when compared to the line crossings method with manual scoring. In addition, VTS enables high-throughput experimentation. While similar to automated video tracking used for the open field test (OFT), LMA testing is unique in that it allows mice to remain in their home cage and does not utilize the anxiogenic stimulus of bright lighting during the active phase of the light-dark cycle. Traditionally, LMA has been used for short periods of time (mins), while longer movement studies (hrs-days) have often used implanted transmitters and biotelemetry. With the option of real-time tracking, long-, like short-term LMA testing, can now be conducted using videography. Long-term LMA testing requires a specialized, but easily constructed, cage so that food and water (which is usually positioned on the cage top) does not obstruct videography. Importantly, videography and VTS allows for the quantification of parameters, such as path of mouse movement, that are difficult or unfeasible to measure with line crossing and/or biotelemetry. In sum, LMA testing coupled to VTS affords a more complete description of mouse movement and the ability to examine locomotion over an extended period of time.

  18. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

    Science.gov (United States)

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

    2014-01-01

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

  19. Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

    Science.gov (United States)

    Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

    2018-07-02

    Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. [The modified method registration of kinesthetic evoked potentials and its application for research of proprioceptive sensitivity disorders at spondylogenic cervical myelopathy].

    Science.gov (United States)

    Gordeev, S A; Voronin, S G

    2016-01-01

    To analyze the efficacy of modified (passive radiocarpal articulation flexion/extension) and «standard» (passive radiocarpal articulation flexion) methods of kinesthetic evoked potentials for proprioceptive sensitivity assessment in healthy subjects and patients with spondylotic cervical myelopathy. The study included 14 healthy subjects (4 women and 10 men, mean age 54.1±10.5 years) and 8 patients (2 women and 6 men, mean age 55.8±10.9 years) with spondylotic cervical myelopathy. Muscle-joint sensation was examined during the clinical study. A modified method of kinesthetic evoked potentials was developed. This method differed from the "standard" one by the organization of a cycle including several passive movements,where each new movement differed from the preceding one by the direction. The modified method of kinesthetic evoked potentials ensures more reliable kinesthetic sensitivity assessment due to movement variability. Asignificant increaseof the latent periods of the early components of the response was found in patients compared to healthy subjects. The modified method of kinesthetic evoked potentials can be used for objective diagnosis of proprioceptive sensitivity disorders in patients with spondylotic cervical myelopathy.

  1. Assessment of the potential impacts of plant traits across environments by combining global sensitivity analysis and dynamic modeling in wheat

    OpenAIRE

    Casadebaig, Pierre; Zheng, Bangyou; Chapman, Scott; Huth, Neil; Faivre, Robert; Chenu, Karine

    2015-01-01

    A crop can be viewed as a complex system with outputs (e.g. yield) that are affected by inputs of genetic, physiology, pedo-climatic and management information. Application of numerical methods for model exploration assist in evaluating the major most influential inputs, providing the simulation model is a credible description of the biological system. A sensitivity analysis was used to assess the simulated impact on yield of a suite of traits involved in major processes of crop growth and de...

  2. Acetylcholinesterase inhibition and altered locomotor behavior in the carabid beetle pterostichus

    DEFF Research Database (Denmark)

    Jensen, Charlotte S.; Krause-Jensen, Lone; Baatrup, Erik

    1997-01-01

    -aided video tracking, whereupon the whole body AChE activity was measured in the individual beetle. AChE inhibition was strongly correlated with dimethoate dose in both sexes. Alterations in the locomotor behavior were directly correlated with AChE inhibition in male beetles, which responded by reducing...... to locomotor behavior, representing a general effect biomarker at the organismal level. Both sexes of the carabid beetle Pterostichus cupreus were intoxicated with three doses of the organophosphorous insecticide dimethoate. Five elements of their locomotor behavior were measured for 4 h employing computer...... the time in locomotion, average velocity, and path length and by increasing the turning rate and frequency of stops. Females responded similarly at the two highest doses, whereas their locomotor behavior was not significantly different from the control group at the lowest dimethoate dose, suggesting a sex...

  3. Effects of cholestasis on learning and locomotor activity in bile duct ligated rats.

    Science.gov (United States)

    Hosseini, Nasrin; Alaei, Hojjatallah; Nasehi, Mohammad; Radahmadi, Maryam; Mohammad Reza, Zarrindast

    2014-01-01

    Cognitive functions are impaired in patients with liver disease. Bile duct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Cholestasis was induced in male Wistar rats by ligating the main bile duct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bile duct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P locomotor activity were impaired at 21 days after bile duct ligation following the progression of cholestasis.

  4. Comparative limb proportions reveal differential locomotor morphofunctions of alligatoroids and crocodyloids

    Science.gov (United States)

    Iijima, Masaya; Kubo, Tai; Kobayashi, Yoshitsugu

    2018-03-01

    Although two major clades of crocodylians (Alligatoroidea and Crocodyloidea) were split during the Cretaceous period, relatively few morphological and functional differences between them have been known. In addition, interaction of multiple morphofunctional systems that differentiated their ecology has barely been assessed. In this study, we examined the limb proportions of crocodylians to infer the differences of locomotor functions between alligatoroids and crocodyloids, and tested the correlation of locomotor and feeding morphofunctions. Our analyses revealed crocodyloids including Gavialis have longer stylopodia (humerus and femur) than alligatoroids, indicating that two groups may differ in locomotor functions. Fossil evidence suggested that alligatoroids have retained short stylopodia since the early stage of their evolution. Furthermore, rostral shape, an indicator of trophic function, is correlated with limb proportions, where slender-snouted piscivorous taxa have relatively long stylopodia and short overall limbs. In combination, trophic and locomotor functions might differently delimit the ecological opportunity of alligatoroids and crocodyloids in the evolution of crocodylians.

  5. Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

    Science.gov (United States)

    Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metric...

  6. Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

    Science.gov (United States)

    Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

    2003-04-01

    It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

  7. Locomotor activity: A distinctive index in morphine self-administration in rats

    OpenAIRE

    Zhang, Jian-Jun; Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with ...

  8. V1 spinal neurons regulate the speed of vertebrate locomotor outputs

    DEFF Research Database (Denmark)

    Gosgnach, Simon; Lanuza, Guillermo M.; Butt, Simon J B

    2006-01-01

    The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord1-3. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioural outputs...... for inhibition in regulating the frequency of the locomotor CPG rhythm, and also suggest that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements....

  9. Ankle voluntary movement enhancement following robotic-assisted locomotor training in spinal cord injury

    OpenAIRE

    Varoqui, Deborah; Niu, Xun; Mirbagheri, Mehdi M

    2014-01-01

    Background In incomplete spinal cord injury (iSCI), sensorimotor impairments result in severe limitations to ambulation. To improve walking capacity, physical therapies using robotic-assisted locomotor devices, such as the Lokomat, have been developed. Following locomotor training, an improvement in gait capabilities—characterized by increases in the over-ground walking speed and endurance—is generally observed in patients. To better understand the mechanisms underlying these improvements, we...

  10. Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

    OpenAIRE

    DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

    2016-01-01

    Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor pr...

  11. Immobility time during the forced swimming test predicts sensitivity to amitriptyline, whereas traveled distance in the circular corridor indicates resistance to treatment in female Wistar rats.

    Science.gov (United States)

    Flores-Serrano, Ana G; Zaldívar-Rae, Jaime; Salgado, Humberto; Pineda, Juan C

    2015-03-25

    Among the main issues in the pharmacological treatment of depression are the wide variation in response to antidepressants among individual patients and the lack of indexes that allow prediction of which drug will be effective in a particular case. We evaluated whether differential sensitivity to amitriptyline is related to dichotomous categorization of individuals on the basis of their behavioral responses to two common paradigms used to evaluate the potential of tricyclic drugs as antidepressants. Hence, we categorized a cohort of 38 female rats on the basis of their immobility time in the conditioning phase of the forced swimming test [FST; high immobility (HI) vs. low immobility (LI) rats] and their locomotor behavior in the circular corridor test [high locomotor response (HR) vs. low locomotor response (LR) rats]. We subjected the rodents to the FST while under the influence of vehicle (n=20) or amitriptyline (15 mg/kg; n=18). We found no statistical evidence of dependence between categorizations of rats on the basis of their behavior in the FST and circular corridor test. Rats categorized as HI/LI and HR/LR significantly differed in their sensitivity/resistance to amitriptyline, as evidenced by changes (or lack thereof) in their immobility time, climbing time, and swimming time during the FST. These results confirm that different behavioral styles among rats are linked to differential sensitivity/resistance to antidepressants. However, we specifically found that categorizing rats as HI/LI better reflected sensitivity to amitriptyline, whereas categorizing them as HR/LR better revealed resistance to the drug. These differential responses should be considered in experimental approaches. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  12. Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

    Science.gov (United States)

    Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

    2017-06-01

    Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The scid mutation does not affect slowly repairing potentially lethal damage that is sensitive to 0.23 M NaCl

    International Nuclear Information System (INIS)

    Kimura, Hiroshi; Ikebuchi, Makoto; Fushiki, Masato; Komatsu, Kenshi.

    1996-01-01

    The repair of slowly repairing potentially lethal damage (PLD) in radiosensitive cells from the severe combined immunodeficient (scid) mouse was compared with that in Balb/c 3T3 cells with ''wild-type'' radiosensitivity and that in RD13B2 cells derived from scid cells whose sensitivity is normal because of the presence of fragments of human chromosome 8. Treatment with 0.23 M NaCl was used for fixation of slowly repairing PLD. The scid cells repaired PLD sensitive to 0.23 M NaCl to a great extent whin 3-4 h, similarly to Balb/c 3T3 and RD13B2 cells. This indicates that the scid mutation hardly affects the repair of PLD sensitive to 0.23 M NaCl. On the other hand, as reported previously, the rapidly repairing PLD that is sensitive to 0.5 M NaCl was repaired only slowly (3-4 h) in scid cells, in contrast to the rapid repair (within 1 h) seen with Balb/c 3T3 and RD13B2. This suggests that scid mutation is responsible for this repair at reduced rate. To confirm the independence of repair of 0.23 M NaCl-sensitive PLD from that of 0.5 M NaCl-sensitive PLD, both treatments with 0.23 M NaCl and 0.5 M NaCl were combined in each line. It is found that the repair of either PLD was not affected by the other treatment. The scid mutation impaired only the repair of 0.5 M NaCl-sensitive PLD. (author)

  14. A Quantitative Risk Assessment of the Skin Sensitization Induction Potential of the Kathon CG Preservative in Rinse-off and Leave-on Personal Care and Cosmetic Products.

    Science.gov (United States)

    Towle, Kevin M; Drechsel, Derek A; Warshaw, Erin M; Fung, Ernest S; Novick, Rachel M; Paustenbach, Dennis J; Monnot, Andrew D

    2018-03-22

    Kathon CG is a commonly used cosmetic-grade preservative that contains active ingredients methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI). The aim of the study was to perform a skin sensitization induction risk assessment of daily exposure to Kathon CG after use of various personal care and cosmetic products. We calculated an estimated daily consumer exposure level for rinse-off and leave-on products using the amount of product applied per application, number of applications per day, a retention factor, the MCI/MI concentration, and body surface area values. We assumed that the products contained the maximum recommended safe concentration of MCI/MI: 15 ppm in rinse-off products and 7.5 ppm in leave-on products. We compared estimated consumer exposure levels with the no expected sensitization induction level for MCI/MI and applied sensitization assessment factors to calculate product-specific margins of safety (MOSs). The MOSs for rinse-off products ranged from 5 to 63, whereas the MOSs for leave-on products ranged from 0.03 to 1.49. Overall, our results provide evidence that some leave-on products containing the maximum recommended safe concentration of Kathon CG may increase the risk of sensitization induction due to exposure to MCI/MI. In contrast, rinse-off products were not associated with a potential increased risk of skin sensitization induction.

  15. Clinical Holistic Medicine: Chronic Pain in the Locomotor System

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    Søren Ventegodt

    2005-01-01

    Full Text Available Most pains from the locomotor system arise due to involuntary, chronic tensions in the muscles or other tissues. When the patient is motivated, the pain is easily cured in most of the cases by using the tools of consciousness-based medicine, primarily therapeutic touch, conversation, and coaching the patient in a positive philosophy of life. The pains are often caused by “blockages” that may cause problems other than just pain. Often it turns out that the blocked areas develop actual physical damage over time: a slipped disk in the back, articular degeneration, or osteoarthritis when the cartilage is affected, can often be explained in this way. Apparently, the exact areas where the blockage is situated cause cellular problems, disrupting cellular order. The holistic process theory of healing and the related quality of life theories state that return to the natural state of being is possible, whenever the person gets the resources needed for existential healing. The resources needed are “holding” in the dimensions of awareness, respect, care, acknowledgment, and acceptance with support and processing in the dimensions of feeling, understanding, and letting go of negative attitudes and beliefs. The preconditions for holistic healing are trust and the intention for the healing to take place. Case stories of holistic treatment of patients with chronic back pain, low back pain, muscle problems, knee pain, and symptoms of rheumatoid arthritis are discussed with exercises relevant for patients with these conditions in the holistic clinic.

  16. Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats.

    Science.gov (United States)

    Melo, Fernanda Rosene; Bressan, Raul Bardini; Forner, Stefânia; Martini, Alessandra Cadete; Rode, Michele; Delben, Priscilla Barros; Rae, Giles Alexander; Figueiredo, Claudia Pinto; Trentin, Andrea Gonçalves

    2017-07-01

    Spinal cord injury (SCI) is a devastating neurologic disorder with significant impacts on quality of life, life expectancy, and economic burden. Although there are no fully restorative treatments yet available, several animal and small-scale clinical studies have highlighted the therapeutic potential of cellular interventions for SCI. Mesenchymal stem cells (MSCs)-which are conventionally isolated from the bone marrow-recently emerged as promising candidates for treating SCI and have been shown to provide trophic support, ameliorate inflammatory responses, and reduce cell death following the mechanical trauma. Here we evaluated the human skin as an alternative source of adult MSCs suitable for autologous cell transplantation strategies for SCI. We showed that human skin-derived MSCs (hSD-MSCs) express a range of neural markers under standard culture conditions and are able to survive and respond to neurogenic stimulation in vitro. In addition, using histological analysis and behavioral assessment, we demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the severity of tissue loss and facilitates locomotor recovery in a rat model of SCI. Altogether, the study provides further characterization of skin-derived MSC cultures and indicates that the human skin may represent an attractive source for cell-based therapies for SCI and other neurological disorders. Further investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit tissue repair and/or locomotor recovery.

  17. P(MMA-EMA Random Copolymer Electrolytes Incorporating Sodium Iodide for Potential Application in a Dye-Sensitized Solar Cell

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    Nurul Akmaliah Dzulkurnain

    2015-02-01

    Full Text Available Polymer electrolytes based on 90 wt% of methyl methacrylate and 10 wt% of ethyl methacrylate (90MMA-co-10EMA incorporating different weight ratios of sodium iodide were prepared using the solution casting method. The complexation between salt and copolymer host has been investigated using Fourier transform infrared spectroscopy. The ionic conductivity and thermal stability of the electrolytes were measured using impedance spectroscopy and differential scanning calorimetry, respectively. Scanning electron microscopy was used to study the morphology of the polymer electrolytes. The ionic conductivity and glass transition temperature increased up to 20 wt% of sodium iodide (5.19 × 10−6 S·cm−1 and decreased with the further addition of salt concentration, because of the crosslinked effect. The morphology behavior of the highest conducting sample also showed smaller pores compared to the other concentration. The total ionic transference number proved that this system was mainly due to ions, and the electrochemical stability window was up to 2.5 V, which is suitable for a dye-sensitized solar cell application. This sample was then tested in a dye-sensitized solar cell and exhibited an efficiency of 0.62%.

  18. APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.

    Science.gov (United States)

    Ryu, Jiyoon; Galan, Amanda K; Xin, Xiaoban; Dong, Feng; Abdul-Ghani, Muhammad A; Zhou, Lijun; Wang, Changhua; Li, Cuiling; Holmes, Bekke M; Sloane, Lauren B; Austad, Steven N; Guo, Shaodong; Musi, Nicolas; DeFronzo, Ralph A; Deng, Chuxia; White, Morris F; Liu, Feng; Dong, Lily Q

    2014-05-22

    Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Abuse potential and adverse cognitive effects of mitragynine (kratom).

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    Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

    2016-01-01

    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug. © 2014 Society for the Study of Addiction.

  20. Chronic exposure to MDMA (Ecstasy elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

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    Swann Alan C

    2006-01-01

    Full Text Available Abstract Background The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA. Methods The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg and a saline control group (N = 9/group. All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13. Rats were then given an additional 25-day washout period, and re-challenged (day 38 with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39. Open-field locomotor activity was recorded using a computerized automated activity monitoring system. Results Acute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group, while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change

  1. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

    Science.gov (United States)

    Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

    2015-05-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

  2. Effect of Error Augmentation on Brain Activation and Motor Learning of a Complex Locomotor Task

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    Laura Marchal-Crespo

    2017-09-01

    Full Text Available Up to date, the functional gains obtained after robot-aided gait rehabilitation training are limited. Error augmenting strategies have a great potential to enhance motor learning of simple motor tasks. However, little is known about the effect of these error modulating strategies on complex tasks, such as relearning to walk after a neurologic accident. Additionally, neuroimaging evaluation of brain regions involved in learning processes could provide valuable information on behavioral outcomes. We investigated the effect of robotic training strategies that augment errors—error amplification and random force disturbance—and training without perturbations on brain activation and motor learning of a complex locomotor task. Thirty-four healthy subjects performed the experiment with a robotic stepper (MARCOS in a 1.5 T MR scanner. The task consisted in tracking a Lissajous figure presented on a display by coordinating the legs in a gait-like movement pattern. Behavioral results showed that training without perturbations enhanced motor learning in initially less skilled subjects, while error amplification benefited better-skilled subjects. Training with error amplification, however, hampered transfer of learning. Randomly disturbing forces induced learning and promoted transfer in all subjects, probably because the unexpected forces increased subjects' attention. Functional MRI revealed main effects of training strategy and skill level during training. A main effect of training strategy was seen in brain regions typically associated with motor control and learning, such as, the basal ganglia, cerebellum, intraparietal sulcus, and angular gyrus. Especially, random disturbance and no perturbation lead to stronger brain activation in similar brain regions than error amplification. Skill-level related effects were observed in the IPS, in parts of the superior parietal lobe (SPL, i.e., precuneus, and temporal cortex. These neuroimaging findings

  3. Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer.

    Science.gov (United States)

    Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

    2014-01-21

    Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments. In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by (1)H-magnetic spectroscopy analysis; (III) a 35-36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context. We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with conventional drugs.

  4. Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the Lou/C rat.

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    Christelle Veyrat-Durebex

    Full Text Available The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3 ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3, known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF and thyrotropin-releasing hormone (TRH.

  5. DFT and TD-DFT calculations of metallotetraphenylporphyrin and metallotetraphenylporphyrin fullerene complexes as potential dye sensitizers for solar cells

    Science.gov (United States)

    El Mahdy, A. M.; Halim, Shimaa Abdel; Taha, H. O.

    2018-05-01

    Density functional theory (DFT) and time-dependent DFT calculations have been employed to model metallotetraphenylporphyrin dyes and metallotetraphenylporphyrin -fullerene complexes in order to investigate the geometries, electronic structures, the density of states, non-linear optical properties (NLO), IR-vis spectra, molecular electrostatic potential contours, and electrophilicity. To calculate the excited states of the tetraphenyl porphyrin analogs, time-dependent density functional theory (TD-DFT) are used. Their UV-vis spectra were also obtained and a comparison with available experimental and theoretical results is included. The results reveal that the metal and the tertiary butyl groups of the dyes are electron donors, and the tetraphenylporphyrin rings are electron acceptors. The HOMOs of the dyes fall within the (TiO2)60 and Ti38O76 band gaps and support the issue of typical interfacial electron transfer reaction. The resulting potential drop of Mn-TPP-C60 increased by ca. 3.50% under the effect of the tertiary butyl groups. The increase in the potential drop indicates that the tertiary butyl complexes could be a better choice for the strong operation of the molecular rectifiers. The introduction of metal atom and tertiary butyl groups to the tetraphenyl porphyrin moiety leads to a stronger response to the external electric field and induces higher photo-to-current conversion efficiency. This also shifts the absorption in the dyes and makes them potential candidates for harvesting light in the entire visible and near IR region for photovoltaic applications.

  6. "On the Fence" versus "All in": Insights from Turtles for the Evolution of Aquatic Locomotor Specializations and Habitat Transitions in Tetrapod Vertebrates.

    Science.gov (United States)

    Blob, Richard W; Mayerl, Christopher J; Rivera, Angela R V; Rivera, Gabriel; Young, Vanessa K H

    2016-12-01

    Though ultimately descended from terrestrial amniotes, turtles have deep roots as an aquatic lineage and are quite diverse in the extent of their aquatic specializations. Many taxa can be viewed as "on the fence" between aquatic and terrestrial realms, whereas others have independently hyperspecialized and moved "all in" to aquatic habitats. Such differences in specialization are reflected strongly in the locomotor system. We have conducted several studies to evaluate the performance consequences of such variation in design, as well as the mechanisms through which specialization for aquatic locomotion is facilitated in turtles. One path to aquatic hyperspecialization has involved the evolutionary transformation of the forelimbs from rowing, tubular limbs with distal paddles into flapping, flattened flippers, as in sea turtles. Prior to the advent of any hydrodynamic advantages, the evolution of such flippers may have been enabled by a reduction in twisting loads on proximal limb bones that accompanied swimming in rowing ancestors, facilitating a shift from tubular to flattened limbs. Moreover, the control of flapping movements appears related primarily to shifts in the activity of a single forelimb muscle, the deltoid. Despite some performance advantages, flapping may entail a locomotor cost in terms of decreased locomotor stability. However, other morphological specializations among rowing species may enhance swimming stability. For example, among highly aquatic pleurodiran turtles, fusion of the pelvis to the shell appears to dramatically reduce motions of the pelvis compared to freshwater cryptodiran species. This could contribute to advantageous increases in aquatic stability among predominantly aquatic pleurodires. Thus, even within the potential constraints of a body plan in which the body is encased by a shell, turtles exhibit diverse locomotor capacities that have enabled diversification into a wide range of aquatic habitats. © The Author 2016. Published

  7. “On the Fence” versus “All in”: Insights from Turtles for the Evolution of Aquatic Locomotor Specializations and Habitat Transitions in Tetrapod Vertebrates

    Science.gov (United States)

    Blob, Richard W.; Mayerl, Christopher J.; Rivera, Angela R. V.; Rivera, Gabriel; Young, Vanessa K. H.

    2016-01-01

    Though ultimately descended from terrestrial amniotes, turtles have deep roots as an aquatic lineage and are quite diverse in the extent of their aquatic specializations. Many taxa can be viewed as “on the fence” between aquatic and terrestrial realms, whereas others have independently hyperspecialized and moved “all in” to aquatic habitats. Such differences in specialization are reflected strongly in the locomotor system. We have conducted several studies to evaluate the performance consequences of such variation in design, as well as the mechanisms through which specialization for aquatic locomotion is facilitated in turtles. One path to aquatic hyperspecialization has involved the evolutionary transformation of the forelimbs from rowing, tubular limbs with distal paddles into flapping, flattened flippers, as in sea turtles. Prior to the advent of any hydrodynamic advantages, the evolution of such flippers may have been enabled by a reduction in twisting loads on proximal limb bones that accompanied swimming in rowing ancestors, facilitating a shift from tubular to flattened limbs. Moreover, the control of flapping movements appears related primarily to shifts in the activity of a single forelimb muscle, the deltoid. Despite some performance advantages, flapping may entail a locomotor cost in terms of decreased locomotor stability. However, other morphological specializations among rowing species may enhance swimming stability. For example, among highly aquatic pleurodiran turtles, fusion of the pelvis to the shell appears to dramatically reduce motions of the pelvis compared to freshwater cryptodiran species. This could contribute to advantageous increases in aquatic stability among predominantly aquatic pleurodires. Thus, even within the potential constraints of a body plan in which the body is encased by a shell, turtles exhibit diverse locomotor capacities that have enabled diversification into a wide range of aquatic habitats. PMID:27940619

  8. Cell phone-generated radio frequency electromagnetic field effects on the locomotor behaviors of the fishes Poecilia reticulata and Danio rerio.

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    Lee, David; Lee, Joshua; Lee, Imshik

    2015-01-01

    The locomotor behavior of small fish was characterized under a cell phone-generated radio frequency electromagnetic field (RF EMF). The trajectory of movement of 10 pairs of guppy (Poecilia reticulate) and 15 pairs of Zebrafish (Danio rerio) in a fish tank was recorded and tracked under the presence of a cell phone-generated RF EMF. The measures were based on spatial and temporal distributions. A time-series trajectory was utilized to emphasize the dynamic nature of locomotor behavior. Fish movement was recorded in real-time. Their spatial, velocity, turning angle and sinuosity distribution were analyzed in terms of F(v,x), P[n(x,t)], P(v), F (θ) and F(s), respectively. In addition, potential temperature elevation caused by a cellular phone was also examined. We demonstrated that a cellular phone-induced temperature elevation was not relevant, and that our measurements reflected RF EMF-induced effects on the locomotor behavior of Poecilia reticulata and Danio rerio. Fish locomotion was observed under normal conditions, in the visual presence of a cell phone, after feeding, and under starvation. Fish locomotor behavior was random both in normal conditions and in the presence of an off-signaled cell phone. However, there were significant changes in the locomotion of the fish after feeding under the RF EMF. The locomotion of the fed fish was affected in terms of changes in population and velocity distributions under the presence of the RF EMF emitted by the cell phone. There was, however, no significant difference in angular distribution.

  9. Adaptive evolution in locomotor performance: How selective pressures and functional relationships produce diversity.

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    Scales, Jeffrey A; Butler, Marguerite A

    2016-01-01

    Despite the complexity of nature, most comparative studies of phenotypic evolution consider selective pressures in isolation. When competing pressures operate on the same system, it is commonly expected that trade-offs will occur that will limit the evolution of phenotypic diversity, however, it is possible that interactions among selective pressures may promote diversity instead. We explored the evolution of locomotor performance in lizards in relation to possible selective pressures using the Ornstein-Uhlenbeck process. Here, we show that a combination of selection based on foraging mode and predator escape is required to explain variation in performance phenotypes. Surprisingly, habitat use contributed little explanatory power. We find that it is possible to evolve very different abilities in performance which were previously thought to be tightly correlated, supporting a growing literature that explores the many-to-one mapping of morphological design. Although we generally find the expected trade-off between maximal exertion and speed, this relationship surprisingly disappears when species experience selection for both performance types. We conclude that functional integration need not limit adaptive potential, and that an integrative approach considering multiple major influences on a phenotype allows a more complete understanding of adaptation and the evolution of diversity. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  10. A locomotor innovation enables water-land transition in a marine fish.

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    Shi-Tong Tonia Hsieh

    Full Text Available BACKGROUND: Morphological innovations that significantly enhance performance capacity may enable exploitation of new resources and invasion of new ecological niches. The invasion of land from the aquatic realm requires dramatic structural and physiological modifications to permit survival in a gravity-dominated, aerial environment. Most fishes are obligatorily aquatic, with amphibious fishes typically making slow-moving and short forays on to land. METHODOLOGY/PRINCIPAL FINDINGS: Here I describe the behaviors and movements of a little known marine fish that moves extraordinarily rapidly on land. I found that the Pacific leaping blenny, Alticus arnoldorum, employs a tail-twisting movement on land, previously unreported in fishes. Focal point behavioral observations of Alticus show that they have largely abandoned the marine realm, feed and reproduce on land, and even defend terrestrial territories. Comparisons of these blennies' terrestrial kinematic and kinetic (i.e., force measurements with those of less terrestrial sister genera show A. arnoldorum move with greater stability and locomotor control, and can move away more rapidly from impending threats. CONCLUSIONS/SIGNIFICANCE: My results demonstrate that axial tail twisting serves as a key innovation enabling invasion of a novel marine niche. This paper highlights the potential of using this system to address general evolutionary questions about water-land transitions and niche invasions.

  11. Corticospinal Reorganization after Locomotor Training in a Person with Motor Incomplete Paraplegia

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    Nupur Hajela

    2013-01-01

    Full Text Available Activity-dependent plasticity as a result of reorganization of neural circuits is a fundamental characteristic of the central nervous system that occurs simultaneously in multiple sites. In this study, we established the effects of subthreshold transcranial magnetic stimulation (TMS over the primary motor cortex region on the tibialis anterior (TA long-latency flexion reflex. Neurophysiological tests were conducted before and after robotic gait training in one person with a motor incomplete spinal cord injury (SCI while at rest and during robotic-assisted stepping. The TA flexion reflex was evoked following nonnociceptive sural nerve stimulation and was conditioned by TMS at 0.9 TA motor evoked potential resting threshold at conditioning-test intervals that ranged from 70 to 130 ms. Subthreshold TMS induced a significant facilitation on the TA flexion reflex before training, which was reversed to depression after training with the subject seated at rest. During stepping, corticospinal facilitation of the flexion reflex at early and midstance phases before training was replaced with depression at early and midswing followed by facilitation at late swing after training. These results constitute the first neurophysiologic evidence that locomotor training reorganizes the cortical control of spinal interneuronal circuits that generate patterned motor activity, modifying spinal reflex function, in the chronic lesioned human spinal cord.

  12. A model-based exploration of the role of pattern generating circuits during locomotor adaptation.

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    Marjaninejad, Ali; Finley, James M

    2016-08-01

    In this study, we used a model-based approach to explore the potential contributions of central pattern generating circuits (CPGs) during adaptation to external perturbations during locomotion. We constructed a neuromechanical modeled of locomotion using a reduced-phase CPG controller and an inverted pendulum mechanical model. Two different forms of locomotor adaptation were examined in this study: split-belt treadmill adaptation and adaptation to a unilateral, elastic force field. For each simulation, we first examined the effects of phase resetting and varying the model's initial conditions on the resulting adaptation. After evaluating the effect of phase resetting on the adaptation of step length symmetry, we examined the extent to which the results from these simple models could explain previous experimental observations. We found that adaptation of step length symmetry during split-belt treadmill walking could be reproduced using our model, but this model failed to replicate patterns of adaptation observed in response to force field perturbations. Given that spinal animal models can adapt to both of these types of perturbations, our findings suggest that there may be distinct features of pattern generating circuits that mediate each form of adaptation.

  13. Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury

    Science.gov (United States)

    Hansen, Christopher N.; Norden, Diana M.; Faw, Timothy D.; Deibert, Rochelle; S.Wohleb, Eric; Sheridan, John F.; P.Godbout, Jonathan; Basso, D. Michele

    2016-01-01

    Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24 hours and 7 days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24 hours after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7 days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9. PMID:27191729

  14. Microgeographic variation in locomotor traits among lizards in a human-built environment

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    Colin Donihue

    2016-03-01

    Full Text Available Microgeographic variation in fitness-relevant traits may be more common than previously appreciated. The fitness of many vertebrates is directly related to their locomotor capacity, a whole-organism trait integrating behavior, morphology, and physiology. Because locomotion is inextricably related to context, I hypothesized that it might vary with habitat structure in a wide-ranging lizard, Podarcis erhardii, found in the Greek Cyclade Islands. I compared lizard populations living on human-built rock walls, a novel habitat with complex vertical structure, with nearby lizard populations that are naive to human-built infrastructure and live in flat, loose-substrate habitat. I tested for differences in morphology, behavior, and performance. Lizards from built sites were larger and had significantly (and relatively longer forelimbs and hindlimbs. The differences in hindlimb morphology were especially pronounced for distal components—the foot and longest toe. These morphologies facilitated a significant behavioral shift in jumping propensity across a rocky experimental substrate. I found no difference in maximum velocity between these populations; however, females originating from wall sites potentially accelerated faster over the rocky experimental substrate. The variation between these closely neighboring populations suggests that the lizards inhabiting walls have experienced a suite of trait changes enabling them to take advantage of the novel habitat structure created by humans.

  15. Locomotor damage in rats after x-irradiation in Utero

    International Nuclear Information System (INIS)

    Mullenix, P.; Norton, S.; Culver, B.

    1975-01-01

    Alterations in gait were found in rats after whole-body irradiation with 125 R on day 14, 15, and 16 of gestation. No effects on locomotion were detected after irradiation on day 17 with 125 R or after irradiation on day 14 with 50 R. A technique was set up for quantitative evaluation of locomotion based on a modification of other methods. Walking patterns of irradiated rats were recorded, when they were adults, by requiring them to walk up a 10 0 incline through a corridor after their feet had been dipped in ink. Rats irradiated on gestational day 14 had an in-phase, hopping gait with the sine of the angle between the hind feet and the direction of progression over 0.9. Rats irradiated on gestational days 15 and 16 had an alternating, waddling gait with wider stance and broader angle than control rats. Histologic examination of serial sections of the brains of these rats showed that the 14-day rats lacked all telencephalic commissures except for a few fibers which crossed in some rats. There was a progressive improvement in the condition of the anterior and ventral hippocampal commissures up to day 17, but the corpus callosum and doral hippocampal commissure were lacking or markedly reduced in all day 17 rats. No animals showed damage to the mesencephalic posterior commissure. Since rats which used the in-phase mode of locomotion were never observed to use alternating gait, the possible causal relationship of the commissural damage to the altered locomotor patterns was considered. In view of the restricted period of damage found for the anterior and ventral hippocampal commissures and the restriction of altered locomotion to damage in the same period, primary involvement of the corpus callosum and dorsal hippocampal commissure could be excluded, but a possible role for the other telencephalic commissures remained

  16. General and Specific Strategies Used to Facilitate Locomotor Maneuvers.

    Directory of Open Access Journals (Sweden)

    Mengnan Wu

    Full Text Available People make anticipatory changes in gait patterns prior to initiating a rapid change of direction. How they prepare will change based on their knowledge of the maneuver. To investigate specific and general strategies used to facilitate locomotor maneuvers, we manipulated subjects' ability to anticipate the direction of an upcoming lateral "lane-change" maneuver. To examine specific anticipatory adjustments, we observed the four steps immediately preceding a maneuver that subjects were instructed to perform at a known time in a known direction. We hypothesized that to facilitate a specific change of direction, subjects would proactively decrease margin of stability in the future direction of travel. Our results support this hypothesis: subjects significantly decreased lateral margin of stability by 69% on the side ipsilateral to the maneuver during only the step immediately preceding the maneuver. This gait adaptation may have improved energetic efficiency and simplified the control of the maneuver. To examine general anticipatory adjustments, we observed the two steps immediately preceding the instant when subjects received information about the direction of the maneuver. When the maneuver direction was unknown, we hypothesized that subjects would make general anticipatory adjustments that would improve their ability to actively initiate a maneuver in multiple directions. This second hypothesis was partially supported as subjects increased step width and stance phase hip flexion during these anticipatory steps. These modifications may have improved subjects' ability to generate forces in multiple directions and maintain equilibrium during the onset and execution of the rapid maneuver. However, adapting these general anticipatory strategies likely incurred an additional energetic cost.

  17. Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT).

    Science.gov (United States)

    Kreiling, R; Hollnagel, H M; Hareng, L; Eigler, D; Lee, M S; Griem, P; Dreessen, B; Kleber, M; Albrecht, A; Garcia, C; Wendel, A

    2008-06-01

    The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon-carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI)> or = 3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.

  18. Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

    Science.gov (United States)

    Haralanov, Svetlozar; Haralanova, Evelina; Milushev, Emil; Shkodrova, Diana; Claussen, Claus-Frenz

    2018-04-17

    Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the

  19. Determinants of locomotor disability in people aged 55 years and over: The Rotterdam study

    International Nuclear Information System (INIS)

    Odding, Else; Valkenburg, Hans A.; Stam, Hendrik J.; Hofman, Albert

    2001-01-01

    Locomotor disability, as defined by difficulties in activities of daily living related to lower limb function, can be the consequence of diseases and impairments of the cardiovascular, pulmonary, nervous, sensory and musculoskeletal system. We estimated the associations between specific diseases and impairments and locomotor disability, and the proportion of disability attributable to each condition, controlling for age and comorbidity. The Rotterdam Study is a prospective follow-up study among people aged 55 years and over in the general population. Locomotor disability in 1219 men and 1856 women was assessed with the Stanford Health Assessment Questionnaire. Diseases and impairments were radiological osteoarthritis, pain of the hips and knees, morning stiffness, fractures, hypertension, vascular disease, ischemic heart disease, stroke, heart failure, chronic obstructive pulmonary disease (COPD), depression, Parkinson's disease, osteoporosis, diabetes mellitus, overweight, and low vision. Adjusted odds ratios, etiologic and attributable fractions were calculated for locomotor disability. The occurrence of locomotor disability can partly be ascribed to joint pain, COPD, morning stiffness, diabetes and heart failure in both men and women. In addition in women osteoarthritis, osteoporosis, low vision, fractures, stroke and Parkinson's disease are significant etiologic fractions. In men with morning stiffness, joint pain, heart failure, diabetes mellitus, and COPD a significant proportion of their disability is attributable to this impairment. In women this was the case for Parkinson's disease, morning stiffness, low vision, heart failure, joint pain, diabetes, radiological osteoarthritis, stroke, COPD, osteoporosis, and fractures of the lower limbs, in that order. We conclude that locomotor complaints, heart failure, COPD and diabetes mellitus contribute considerably to locomotor disability in non-institutionalized elderly people

  20. The Effects of Sex-Ratio and Density on Locomotor Activity in the House Fly, Musca domestica

    OpenAIRE

    Bahrndorff, Simon; Kjærsgaard, Anders; Pertoldi, Cino; Loeschcke, Volker; Schou, Toke M.; Skovgård, Henrik; Hald, Birthe

    2012-01-01

    Although locomotor activity is involved in almost all behavioral traits, there is a lack of knowledge on what factors affect it. This study examined the effects of sex-ratio and density on the circadian rhythm of locomotor activity of adult Musca domestica L. (Diptera: Muscidae) using an infra-red light system. Sex-ratio significantly affected locomotor activity, increasing with the percentage of males in the vials. In accordance with other studies, males were more active than females, but th...

  1. Antioxidants keep the potentially probiotic but highly oxygen-sensitive human gut bacterium Faecalibacterium prausnitzii alive at ambient air.

    Directory of Open Access Journals (Sweden)

    M Tanweer Khan

    Full Text Available The beneficial human gut microbe Faecalibacterium prausnitzii is a 'probiotic of the future' since it produces high amounts of butyrate and anti-inflammatory compounds. However, this bacterium is highly oxygen-senstive, making it notoriously difficult to cultivate and preserve. This has so far precluded its clinical application in the treatment of patients with inflammatory bowel diseases. The present studies were therefore aimed at developing a strategy to keep F. prausnitzii alive at ambient air. Our previous research showed that F. prausnitzii can survive in moderately oxygenized environments like the gut mucosa by transfer of electrons to oxygen. For this purpose, the bacterium exploits extracellular antioxidants, such as riboflavin and cysteine, that are abundantly present in the gut. We therefore tested to what extent these antioxidants can sustain the viability of F. prausnitzii at ambient air. The present results show that cysteine can facilitate the survival of F. prausnitzii upon exposure to air, and that this effect is significantly enhanced the by addition of riboflavin and the cryoprotectant inulin. The highly oxygen-sensitive gut bacterium F. prausnitzii can be kept alive at ambient air for 24 h when formulated with the antioxidants cysteine and riboflavin plus the cryoprotectant inulin. Improved formulations were obtained by addition of the bulking agents corn starch and wheat bran. Our present findings pave the way towards the biomedical exploitation of F. prausnitzii in redox-based therapeutics for treatment of dysbiosis-related inflammatory disorders of the human gut.

  2. Design of a Versatile pH-Responsive Hydrogel for Potential Oral Delivery of Gastric-Sensitive Bioactives

    Directory of Open Access Journals (Sweden)

    Angus R. Hibbins

    2017-09-01

    Full Text Available A pH-responsive hydrogel system was prepared by free radical polymerization of acrylamide and methyl acrylic acid in the presence of N-N′-methylene bisacrylamide. Sodium bicarbonate was further applied as a blowing agent, which afforded a porous hydrogel structure. The hydrogel system achieved a constant super swelling rate within simulated intestinal buffer (~4%/min and remained relatively static within simulated gastric buffer (~0.8%/min. The hydrogel system was able to achieve matrix resilience greater than 30% under a relatively high strain of 40%. In addition, the hydrogel system demonstrated significant swelling properties in response to simulated intestinal environmental over 24 h, with contrasting characteristics in simulated gastric buffer. The hydrogel demonstrated type IV isotherm porosity characteristics, with remarkable MRI and SEM variations in gastric and intestinal simulated fluids. Drug loading was observed to be greater than 98% using theophylline as a prototype drug, evaluating its controlled release kinetics over 24 h. The hydrogel exhibited substantial pH-responsive activity, which could be used as a versatile platform for targeted release of gastric-sensitive therapeutics to the small intestine.

  3. Damage-recognition proteins as a potential indicator of DNA-damage-mediated sensitivity or resistance of human cells to ultraviolet radiation

    International Nuclear Information System (INIS)

    Chao, C.C.-K.

    1992-01-01

    The authors compared damage-recognition proteins in cells expressing different sensitivities to DNA damage. An increase in damage-recognition proteins and an enhancement of plasmid re-activation were detected in HeLa cells resistant to cisplatin and u.v. However, repair-defective cells derived from xeroderma-pigmentosum (a rare skin disease) patients did not express less cisplatin damage-recognition proteins than repair-competent cells, suggesting that damage-recognition-protein expression may not be related to DNA repair. By contrast, cells resistant to DNA damage consistently expressed high levels of u.v.-modified-DNA damage-recognition proteins. The results support the notion that u.v. damage-recognition proteins are different from those that bind to cisplatin. Findings also suggest that the damage-recognition proteins identified could be used as potential indicators of the sensitivity or resistance of cells to u.v. (author)

  4. 1-(3-aminopropyl)-3-butylimidazolium bromide for carboxyl group derivatization: potential applications in high sensitivity peptide identification by mass spectrometry.

    Science.gov (United States)

    Qiao, Xiaoqiang; Zhou, Yuan; Hou, Chunyan; Zhang, Xiaodan; Yang, Kaiguang; Zhang, Lihua; Zhang, Yukui

    2013-03-01

    The cationic reagent 1-(3-aminopropyl)-3-butylimidazolium bromide (BAPI) was exploited for the derivatization of carboxyl groups on peptides. Nearly 100% derivatization efficiency was achieved with the synthetic peptide RVYVHPI (RI-7). Furthermore, the peptide derivative was stable in a 0.1% TFA/water solution or a 0.1% (v/v) TFA/acetonitrile/water solution for at least one week. The effect of BAPI derivatization on the ionization of the peptide RI-7 was further investigated, and the detection sensitivity was improved >42-fold via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), thus outperforming the commercial piperazine derivatization approach. Moreover, the charge states of the peptide were largely increased via BAPI derivatization by electrospray ionization (ESI) MS. The results indicate the potential merits of BAPI derivatization for high sensitivity peptide analysis by MS.

  5. Subnanometer Ga 2 O 3 Tunnelling Layer by Atomic Layer Deposition to Achieve 1.1 V Open-Circuit Potential in Dye-Sensitized Solar Cells

    KAUST Repository

    Chandiran, Aravind Kumar

    2012-08-08

    Herein, we present the first use of a gallium oxide tunnelling layer to significantly reduce electron recombination in dye-sensitized solar cells (DSC). The subnanometer coating is achieved using atomic layer deposition (ALD) and leading to a new DSC record open-circuit potential of 1.1 V with state-of-the-art organic D-π-A sensitizer and cobalt redox mediator. After ALD of only a few angstroms of Ga 2O 3, the electron back reaction is reduced by more than an order of magnitude, while charge collection efficiency and fill factor are increased by 30% and 15%, respectively. The photogenerated exciton separation processes of electron injection into the TiO 2 conduction band and the hole injection into the electrolyte are characterized in detail. © 2012 American Chemical Society.

  6. Subnanometer Ga2O3 tunnelling layer by atomic layer deposition to achieve 1.1 V open-circuit potential in dye-sensitized solar cells.

    Science.gov (United States)

    Chandiran, Aravind Kumar; Tetreault, Nicolas; Humphry-Baker, Robin; Kessler, Florian; Baranoff, Etienne; Yi, Chenyi; Nazeeruddin, Mohammad Khaja; Grätzel, Michael

    2012-08-08

    Herein, we present the first use of a gallium oxide tunnelling layer to significantly reduce electron recombination in dye-sensitized solar cells (DSC). The subnanometer coating is achieved using atomic layer deposition (ALD) and leading to a new DSC record open-circuit potential of 1.1 V with state-of-the-art organic D-π-A sensitizer and cobalt redox mediator. After ALD of only a few angstroms of Ga(2)O(3), the electron back reaction is reduced by more than an order of magnitude, while charge collection efficiency and fill factor are increased by 30% and 15%, respectively. The photogenerated exciton separation processes of electron injection into the TiO(2) conduction band and the hole injection into the electrolyte are characterized in detail.

  7. Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats.

    Science.gov (United States)

    Baladi, Michelle G; Koek, Wouter; Aumann, Megan; Velasco, Fortino; France, Charles P

    2012-08-01

    Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats. Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow). After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults. These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

  8. Potential costs of acclimatization to a warmer climate: growth of a reef coral with heat tolerant vs. sensitive symbiont types.

    Directory of Open Access Journals (Sweden)

    Alison Jones

    Full Text Available One of the principle ways in which reef building corals are likely to cope with a warmer climate is by changing to more thermally tolerant endosymbiotic algae (zooxanthellae genotypes. It is highly likely that hosting a more heat-tolerant algal genotype will be accompanied by tradeoffs in the physiology of the coral. To better understand one of these tradeoffs, growth was investigated in the Indo-Pacific reef-building coral Acropora millepora in both the laboratory and the field. In the Keppel Islands in the southern Great Barrier Reef this species naturally harbors nrDNA ITS1 thermally sensitive type C2 or thermally tolerant type D zooxanthellae of the genus Symbiodinium and can change dominant type following bleaching. We show that under controlled conditions, corals with type D symbionts grow 29% slower than those with type C2 symbionts. In the field, type D colonies grew 38% slower than C2 colonies. These results demonstrate the magnitude of trade-offs likely to be experienced by this species as they acclimatize to warmer conditions by changing to more thermally tolerant type D zooxanthellae. Irrespective of symbiont genotype, corals were affected to an even greater degree by the stress of a bleaching event which reduced growth by more than 50% for up to 18 months compared to pre-bleaching rates. The processes of symbiont change and acute thermal stress are likely to act in concert on coral growth as reefs acclimatize to more stressful warmer conditions, further compromising their regeneration capacity following climate change.

  9. Potential Costs of Acclimatization to a Warmer Climate: Growth of a Reef Coral with Heat Tolerant vs. Sensitive Symbiont Types

    Science.gov (United States)

    Jones, Alison; Berkelmans, Ray

    2010-01-01

    One of the principle ways in which reef building corals are likely to cope with a warmer climate is by changing to more thermally tolerant endosymbiotic algae (zooxanthellae) genotypes. It is highly likely that hosting a more heat-tolerant algal genotype will be accompanied by tradeoffs in the physiology of the coral. To better understand one of these tradeoffs, growth was investigated in the Indo-Pacific reef-building coral Acropora millepora in both the laboratory and the field. In the Keppel Islands in the southern Great Barrier Reef this species naturally harbors nrDNA ITS1 thermally sensitive type C2 or thermally tolerant type D zooxanthellae of the genus Symbiodinium and can change dominant type following bleaching. We show that under controlled conditions, corals with type D symbionts grow 29% slower than those with type C2 symbionts. In the field, type D colonies grew 38% slower than C2 colonies. These results demonstrate the magnitude of trade-offs likely to be experienced by this species as they acclimatize to warmer conditions by changing to more thermally tolerant type D zooxanthellae. Irrespective of symbiont genotype, corals were affected to an even greater degree by the stress of a bleaching event which reduced growth by more than 50% for up to 18 months compared to pre-bleaching rates. The processes of symbiont change and acute thermal stress are likely to act in concert on coral growth as reefs acclimatize to more stressful warmer conditions, further compromising their regeneration capacity following climate change. PMID:20454653

  10. Potential costs of acclimatization to a warmer climate: growth of a reef coral with heat tolerant vs. sensitive symbiont types.

    Science.gov (United States)

    Jones, Alison; Berkelmans, Ray

    2010-05-03

    One of the principle ways in which reef building corals are likely to cope with a warmer climate is by changing to more thermally tolerant endosymbiotic algae (zooxanthellae) genotypes. It is highly likely that hosting a more heat-tolerant algal genotype will be accompanied by tradeoffs in the physiology of the coral. To better understand one of these tradeoffs, growth was investigated in the Indo-Pacific reef-building coral Acropora millepora in both the laboratory and the field. In the Keppel Islands in the southern Great Barrier Reef this species naturally harbors nrDNA ITS1 thermally sensitive type C2 or thermally tolerant type D zooxanthellae of the genus Symbiodinium and can change dominant type following bleaching. We show that under controlled conditions, corals with type D symbionts grow 29% slower than those with type C2 symbionts. In the field, type D colonies grew 38% slower than C2 colonies. These results demonstrate the magnitude of trade-offs likely to be experienced by this species as they acclimatize to warmer conditions by changing to more thermally tolerant type D zooxanthellae. Irrespective of symbiont genotype, corals were affected to an even greater degree by the stress of a bleaching event which reduced growth by more than 50% for up to 18 months compared to pre-bleaching rates. The processes of symbiont change and acute thermal stress are likely to act in concert on coral growth as reefs acclimatize to more stressful warmer conditions, further compromising their regeneration capacity following climate change.

  11. Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

    Science.gov (United States)

    Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

    2012-05-01

    Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

  12. Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression.

    Science.gov (United States)

    Press, M F; Hung, G; Godolphin, W; Slamon, D J

    1994-05-15

    HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explantation for the variable overexpression rate reported in the literature.

  13. The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife, Canary Islands, Spain.

    Science.gov (United States)

    Martín-Navarro, Carmen M; Lorenzo-Morales, Jacob; Cabrera-Serra, M Gabriela; Rancel, Fernando; Coronado-Alvarez, Nieves M; Piñero, José E; Valladares, Basilio

    2008-11-01

    Pathogenic strains of the genus Acanthamoeba are causative agents of a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. The prevalence of this infection has risen in the past 20 years, mainly due to the increase in number of contact lens wearers. In this study, the prevalence of Acanthamoeba in a risk group constituted by asymptomatic contact lens wearers from Tenerife, Canary Islands, Spain, was evaluated. Contact lenses and contact lens cases were analysed for the presence of Acanthamoeba isolates. The isolates' genotypes were also determined after rDNA sequencing. The pathogenic potential of the isolated strains was subsequently established using previously described molecular and biochemical assays, which allowed the selection of three strains with high pathogenic potential. Furthermore, the sensitivity of these isolates against two standard drugs, ciprofloxacin and chlorhexidine, was analysed. As the three selected strains were sensitive to chlorhexidine, its activity and IC(50) were evaluated. Chlorhexidine was found to be active against these strains and the obtained IC(50) values were compared to the concentrations of this drug present in contact lens maintenance solutions. It was observed that the measured IC(50) was higher than the concentration found in these maintenance solutions. Therefore, the ineffectiveness of chlorhexidine-containing contact lens maintenance solutions against potentially pathogenic strains of Acanthamoeba is demonstrated in this study.

  14. Potential Influence of Climate Change on the Acid-Sensitivity of High-Elevation Lakes in the Georgia Basin, British Columbia

    Directory of Open Access Journals (Sweden)

    Donna Strang

    2015-01-01

    Full Text Available Global climate models predict increased temperature and precipitation in the Georgia Basin, British Colmbia; however, little is known about the impacts on high-elevation regions. In the current study, fifty-four high-elevation lakes (754–2005 m a.s.l. were studied to investigate the potential influence of climate change on surface water acid-sensitivity. Redundancy analysis indicated that the concentration of nitrate, dissolved organic carbon, and associated metals was significantly influenced by climate parameters. Furthermore, these components differed significantly between biogeoclimatic zones. Modelled soil base cation weathering for a subset of the study lakes (n=11 was predicted to increase by 9% per 1°C increase in temperature. Changes in temperature and precipitation may potentially decrease the pH of surface waters owing to changes in anthropogenic deposition and organic acid production. In contrast, increased soil base cation weathering may increase the critical load (of acidity of high-elevation lakes. Ultimately, the determining factor will be whether enhanced base cation weathering is sufficient to buffer changes in natural and anthropogenic acidity. Mountain and high-elevation regions are considered early warning systems to climate change; as such, future monitoring is imperative to assess the potential ramifications of climate change on the hydrochemistry and acid-sensitivity of these surface waters.

  15. Motor unit recruitment patterns 1: responses to changes in locomotor velocity and incline.

    Science.gov (United States)

    Hodson-Tole, Emma F; Wakeling, James M

    2008-06-01

    Mammalian skeletal muscles are composed of a mixture of motor unit types, which contribute a range of mechanical and physiological properties to the muscle. For a muscle to effectively contribute to smooth, co-ordinated movement it must activate an appropriate number and combination of motor units to generate the required force over a suitable time period. Much evidence exists indicating that motor units are activated in an orderly fashion, from the slowest through to the fastest. A growing body of evidence, however, indicates that such a recruitment strategy does not always hold true. Here we investigate how motor unit recruitment patterns were influenced by changes in locomotor velocity and incline. Kinematics data and myoelectric signals were collected from three rat ankle extensor muscles during running on a treadmill at nine velocity and incline combinations. Wavelet and principal component analysis were used to simultaneously decompose the signals into time and frequency space. The relative frequency components of the signals were quantified during 20 time windows of a stride from each locomotor condition. Differences in signal frequency components existed between muscles and locomotor conditions. Faster locomotor velocities led to a relative increase in high frequency components, whereas greater inclines led to a relative increase in the low frequency components. These data were interpreted as representing changes in motor unit recruitment patterns in response to changes in the locomotor demand. Motor units were not always recruited in an orderly manner, indicating that recruitment is a multi-factorial phenomenon that is not yet fully understood.

  16. Osteological postcranial traits in hylid anurans indicate a morphological continuum between swimming and jumping locomotor modes.

    Science.gov (United States)

    Soliz, Mónica; Tulli, Maria J; Abdala, Virginia

    2017-03-01

    Anurans exhibit a particularly wide range of locomotor modes that result in wide variations in their skeletal structure. This article investigates the possible correlation between morphological aspects of the hylid postcranial skeleton and their different locomotor modes and habitat use. To do so, we analyzed 18 morphometric postcranial variables in 19 different anuran species representative of a variety of locomotor modes (jumper, hopper, walker, and swimmer) and habitat uses (arboreal, bush, terrestrial, and aquatic). Our results show that the evolution of the postcranial hylid skeleton cannot be explained by one single model, as for example, the girdles suggest modular evolution while the vertebral column suggests other evolutionary modules. In conjunction with data from several other studies, we were able to show a relationship between hylid morphology and habitat use; offering further evidence that the jumper/swimmer and walker/hopper locomotor modes exhibit quite similar morphological architecture. This allowed us to infer that new locomotor modalities are, in fact, generated along a morphological continuum. J. Morphol. 278:403-417, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Effect of thiamethoxam on cockroach locomotor activity is associated with its metabolite clothianidin.

    Science.gov (United States)

    Benzidane, Yassine; Touinsi, Sarra; Motte, Emilie; Jadas-Hécart, Alain; Communal, Pierre-Yves; Leduc, Lionel; Thany, Steeve H

    2010-12-01

    In the present study, the effect of thiamethoxam and clothianidin on the locomotor activity of American cockroach, Periplaneta americana (L.), was evaluated. Because it has been proposed that thiamethoxam is metabolised to clothianidin, high-performance liquid chromatography coupled with mass spectrometry was used to evaluate the amount of clothianidin on thiamethoxam-treated cockroaches. One hour after neonicotinoid treatment, the time spent in the open-field-like apparatus significantly increased, suggesting a decrease in locomotor activity. The percentage of cockroaches displaying locomotor activity was significantly reduced 1 h after haemolymph application of 1 nmol g(-1) neonicotinoid, while no significant effect was found after topical and oral administration. However, at 24 and 48 h, all neonicotinoids were able to reduce locomotor activity, depending on their concentrations and the way they were applied. Interestingly, it was found that thiamethoxam was converted to clothianidin 1 h after application, but the amount of clothianidin did not rise proportionately to thiamethoxam, especially after oral administration. The data suggest that the effect of thiamethoxam on cockroach locomotor activity is due in part to clothianidin action because (1) thiamethoxam levels remained persistent 48 h after application and (2) the amount of clothianidin in cockroach tissues was consistent with the toxicity of thiamethoxam. Copyright © 2010 Society of Chemical Industry.

  18. Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Bădescu, S V; Tătaru, C P; Kobylinska, L; Georgescu, E L; Zahiu, D M; Zăgrean, A M; Zăgrean, L

    2016-01-01

    Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations : STZ = streptozotocin, OFT = Open Field Test.

  19. Prediction of preservative sensitization potential using surface marker CD86 and/or CD54 expression on human cell line, THP-1.

    Science.gov (United States)

    Sakaguchi, Hitoshi; Miyazawa, Masaaki; Yoshida, Yukiko; Ito, Yuichi; Suzuki, Hiroyuki

    2007-02-01

    Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This test evaluates the augmentation of CD86 and CD54 expression, which are key events in the sensitization process, as an indicator of allergy following treatment with test chemical. Earlier, we found that a sub-toxic concentration was needed for the up-regulation of surface marker expression. In this study, we further evaluate the capability of h-CLAT to predict allergy potential using eight preservatives. Cytotoxicity was determined using propidium iodide with flow cytometry analysis and five doses that produce a 95, 85, 75, 65, and 50% cell viability were selected. If a material did not have any cytotoxicity at the highest technical dose (HTD), five doses are set using serial 1.3 dilutions of the HTD. The test materials used were six known allergic preservatives (e.g., methylchloroisothiazolinone/methylisothiazolinone, formaldehyde), and two non-allergic preservatives (methylparaben and 4-hydroxybenzoic acid). All allergic preservatives augmented CD86 and/or CD54 expression, indicating h-CLAT correctly identified the allergens. No augmentation was observed with the non-allergic preservatives; also correctly identified by h-CLAT. In addition, we report two threshold concentrations that may be used to categorize skin sensitization potency like the LLNA estimated concentration that yield a three-fold stimulation (EC3) value. These corresponding values are the estimated concentration which gives a relative fluorescence intensity (RFI) = 150 for CD86 and an RFI = 200 for CD54. These data suggest that h-CLAT, using THP-1 cells, may be able to predict the allergy potential of preservatives and

  20. Effect of subacute poisoning with bifenthrin on locomotor activity, memory retention, haematological, biochemical and histopathological parameters in mice.

    Science.gov (United States)

    Nieradko-Iwanicka, B; Borzecki, A; Jodlowska-Jedrych, B

    2015-02-01

    Bifenthrin (BIF) is a pyrethroid (PYR) insecticide. The target point for PYR's toxic action are voltage sensitive sodium channels in the central nervous system (CNS). Intoxication with PYRs results in motor activity impairment and death in insects. Although PYRs are considered to be safe for mammals, there were numerous cases of pyrethroid poisoning in humans, animals and pets described. The general population is chronically exposed to PYRs via grain products, dust and indoor air. Therefore new questions arise: whether PYRs act in a dose-additive fashion in the course of subacute poisoning, are there other target organs (but brain) for BIF and if there is one common mechanism of its' toxic action in different organs. The objective of this work was to characterize the effect of BIF at the doses of 4 or 8 mg/kg injected intraperitoneally (i.p.) daily for 28 consecutive days on memory and motor activity, hematological, biochemical and histopathological parameters in mice. BIF at the doses of 8 mg/kg or 4 mg/kg of body mass was administered i.p. daily to the mice for 28 consecutive days. Motor function was measured on day 1, 7, 14 and 28 and memory retention was tested in a passive avoidance task on day 2, 7, 14 and 28. BIF significantly impaired memory retention on day 2. BIF decreased locomotor activity at every stage of the experiment in a single dose depending manner. No behavioral cumulative effect was observed. Subacute poisoning with the higher dose of BIF caused anaemia, elevated white blood cell count (WBC), elevated alanine transaminase (ALT), superoxide dismuthase (SOD), and decreased glutathione peroxidase (GPx) activity. Lymphocyte infiltrates were visualized in the livers. subacute poisoning with BIF decreases locomotor activity in a single dose proportionate manner. BIF damages also the liver and alters blood morphology. The possible common mechanism of these effects can be oxidative stress.

  1. Intermittent long-wavelength red light increases the period of daily locomotor activity in mice

    Directory of Open Access Journals (Sweden)

    Hughes Amanda M

    2005-05-01

    Full Text Available Abstract Background We observed that a dim, red light-emitting diode (LED triggered by activity increased the circadian periods of lab mice compared to constant darkness. It is known that the circadian period of rats increases when vigorous wheel-running triggers full-spectrum lighting; however, spectral sensitivity of photoreceptors in mice suggests little or no response to red light. Thus, we decided to test the following hypotheses: dim red light illumination triggered by activity (LEDfb increases the circadian period of mice compared to constant dark (DD; covering the LED prevents the effect on period; and DBA2/J mice have a different response to LEDfb than C57BL6/J mice. Methods The irradiance spectra of the LEDs were determined by spectrophotometer. Locomotor activity of C57BL/6J and DBA/2J mice was monitored by passive-infrared sensors and circadian period was calculated from the last 10 days under each light condition. For constant dark (DD, LEDs were switched off. For LED feedback (LEDfb, the red LED came on when the mouse was active and switched off seconds after activity stopped. For taped LED the red LED was switched on but covered with black tape. Single and multifactorial ANOVAs and post-hoc t-tests were done. Results The circadian period of mice was longer under LEDfb than under DD. Blocking the light eliminated the effect. There was no difference in period change in response to LEDfb between C57BL/6 and DBA/2 mice. Conclusion An increase in mouse circadian period due to dim far-red light (1 lux at 652 nm exposure was unexpected. Since blocking the light stopped the response, sound from the sensor's electronics was not the impetus of the response. The results suggest that red light as background illumination should be avoided, and indicator diodes on passive infrared motion sensors should be switched off.

  2. Satellite provided customer promises services, a forecast of potential domestic demand through the year 2000. Volume 4: Sensitivity analysis

    Science.gov (United States)

    Kratochvil, D.; Bowyer, J.; Bhushan, C.; Steinnagel, K.; Kaushal, D.; Al-Kinani, G.

    1984-03-01

    The overall purpose was to forecast the potential United States domestic telecommunications demand for satellite provided customer promises voice, data and video services through the year 2000, so that this information on service demand would be available to aid in NASA program planning. To accomplish this overall purpose the following objectives were achieved: (1) development of a forecast of the total domestic telecommunications demand; (2) identification of that portion of the telecommunications demand suitable for transmission by satellite systems; (3) identification of that portion of the satellite market addressable by consumer promises service (CPS) systems; (4) identification of that portion of the satellite market addressable by Ka-band CPS system; and (5) postulation of a Ka-band CPS network on a nationwide and local level. The approach employed included the use of a variety of forecasting models, a parametric cost model, a market distribution model and a network optimization model. Forecasts were developed for: 1980, 1990, and 2000; voice, data and video services; terrestrial and satellite delivery modes; and C, Ku and Ka-bands.

  3. Prediction of overall persistence and long-range transport potential with multimedia fate models: robustness and sensitivity of results

    International Nuclear Information System (INIS)

    Fenner, Kathrin; Scheringer, Martin; Hungerbuehler, Konrad

    2004-01-01

    The hazard indicators persistence (P) and long-range transport potential (LRTP) are used in chemicals assessment to characterize chemicals with regard to the temporal and spatial extent of their environmental exposure. They are often calculated based on the results of multimedia fate models. The environmental and substance-specific input parameters of such models are subject to a range of methodological uncertainties and also influenced by natural variability. We employed probabilistic uncertainty analysis to quantify variance in P and LRTP predictions for chemicals with different partitioning and transport behavior. Variance found in the results is so large that it prevents a clear distinction between chemicals. Additionally, only small improvements are observed when evaluating the results relative to a benchmark chemical. This can be explained by the dominance of substance-specific parameters and the only small direct influence of environmental parameters on P and LRTP as model outcomes. The findings underline the importance of learning how environmental conditions cause variability in substance behavior for improved substance ranking and classification. - Environmental conditions cause variability in substance behavior which need to be considered in chemical ranking schemes

  4. The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.

    Science.gov (United States)

    de Fiebre, NancyEllen C; Dawson, Ralph; de Fiebre, Christopher M

    2002-06-01

    Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.

  5. Locomotor circumvention strategies are altered by stroke: II. Postural Coordination.

    Science.gov (United States)

    Darekar, Anuja; Lamontagne, Anouk; Fung, Joyce

    2017-06-15

    Locomotor strategies for obstacle circumvention require appropriate postural coordination that depends on sensorimotor integration within the central nervous system. It is not known how these strategies are affected by a stroke. The objective of this study was to contrast postural coordination strategies used for obstacle circumvention between post-stroke participants (n = 12) and healthy controls (n = 12). Participants walked towards a target in a virtual environment (11 × 8 m room) with cylindrical obstacles that were stationary or approaching from head-on, or diagonally 30° left/right. Two stepping strategies for obstacle circumvention were identified: 1) side step: increase in step width by the foot ipsilateral to the side of circumvention; 2) cross step: decrease in step width by the foot contralateral to the side of circumvention. The side step strategy was favoured by post-stroke individuals in circumventing stationary and head-on approaching obstacles. In circumventing diagonally approaching obstacles, healthy controls generally veered opposite to obstacle approach (>60% trials), whereas the majority of post-stroke participants (7/12) veered to the same side of obstacle approach (V same ). Post-stroke participants who veered to the opposite side (V opp , 5/12) were more independent and faster ambulators who favoured the side step strategy in circumventing obstacles approaching from the paretic side and cross step strategy for obstacles approaching from the non-paretic side. V same participants generally favoured the side step strategy for both diagonal approaches. Segmental rotation amplitudes and latencies were largest in the V same group, and significantly greater in post-stroke participants than controls for all obstacle conditions. All participants initiated circumvention with the feet followed by the pelvis and thorax, demonstrating a caudal-rostral sequence of reorientation. Postural coordination strategies for obstacle circumvention

  6. Sensitivity testing of the model set-up used for calculation of photochemical ozone creation potentials (POCP) under European conditions

    Energy Technology Data Exchange (ETDEWEB)

    Altenstedt, J.; Pleijel, K.

    1998-02-01

    Photochemical Ozone Creation Potentials (POCP) is a method to rank VOC, relative to other VOC, according to their ability to produce ground level ozone. To obtain POCP values valid under European conditions, a critical analysis of the POCP concept has been performed using the IVL photochemical trajectory model. The critical analysis has concentrated on three VOC (ethene, n-butane and o-xylene) and has analysed the effect on their POCP values when different model parameters were varied. The three species were chosen because of their different degradation mechanisms in the atmosphere and thus their different abilities to produce ozone. The model parameters which have been tested include background emissions, initial concentrations, dry deposition velocities, the features of the added point source and meteorological parameters. The critical analysis shows that the background emissions of NO{sub x} and VOC have a critical impact on the POCP values. The hour of the day for the point source emission also shows a large influence on the POCP values. Other model parameters which have been studied have not shown such large influence on the POCP values. Based on the critical analysis a model set-up for calculation of POCP is defined. The variations in POCP values due to changes in the background emissions of NO{sub x} and VOC are so large that they can not be disregarded in the calculation of POCP. It is recommended to calculate POCP ranges based on the extremes in POCP values instead of calculating site specific POCP values. Four individual emission scenarios which produced the extremes in POCP values in the analysis have been selected for future calculation of POCP ranges. The scenarios are constructed based on the emissions in Europe and the resulting POCP ranges are thus intended to be applicable within Europe 67 refs, 61 figs, 16 tabs

  7. In-Doped ZnO Hexagonal Stepped Nanorods and Nanodisks as Potential Scaffold for Highly-Sensitive Phenyl Hydrazine Chemical Sensors.

    Science.gov (United States)

    Umar, Ahmad; Kim, Sang Hoon; Kumar, Rajesh; Al-Assiri, Mohammad S; Al-Salami, A E; Ibrahim, Ahmed A; Baskoutas, Sotirios

    2017-11-21

    Herein, we report the growth of In-doped ZnO (IZO) nanomaterials, i.e., stepped hexagonal nanorods and nanodisks by the thermal evaporation process using metallic zinc and indium powders in the presence of oxygen. The as-grown IZO nanomaterials were investigated by several techniques in order to examine their morphological, structural, compositional and optical properties. The detailed investigations confirmed that the grown nanomaterials, i.e., nanorods and nanodisks possess well-crystallinity with wurtzite hexagonal phase and grown in high density. The room-temperature PL spectra exhibited a suppressed UV emissions with strong green emissions for both In-doped ZnO nanomaterials, i.e., nanorods and nanodisks. From an application point of view, the grown IZO nanomaterials were used as a potential scaffold to fabricate sensitive phenyl hydrazine chemical sensors based on the I-V technique. The observed sensitivities of the fabricated sensors based on IZO nanorods and nanodisks were 70.43 μA·mM -1 cm -2 and 130.18 μA·mM -1 cm -2 , respectively. For both the fabricated sensors, the experimental detection limit was 0.5 μM, while the linear range was 0.5 μM-5.0 mM. The observed results revealed that the simply grown IZO nanomaterials could efficiently be used to fabricate highly sensitive chemical sensors.

  8. Terricolous alpine lichens are sensitive to both load and concentration of applied nitrogen and have potential as bioindicators of nitrogen deposition

    International Nuclear Information System (INIS)

    Britton, Andrea J.; Fisher, Julia M.

    2010-01-01

    The influence of applied nitrogen (N) concentration and load on thallus chemistry and growth of five terricolous alpine lichen species was investigated in a three-month N addition study. Thallus N content was influenced by both concentration and load; but the relative importance of these parameters varied between species. Growth was most affected by concentration. Thresholds for effects observed in this study support a low critical load for terricolous lichen communities ( -1 y -1 ) and suggest that concentrations of N currently encountered in UK cloudwater may have detrimental effects on the growth of sensitive species. The significance of N concentration effects on sensitive species also highlights the need to avoid artificially high concentrations when designing N addition experiments. Given the sensitivity of some species to extremely low loads and concentrations of N we suggest that terricolous lichens have potential as indicators of deposition and impact in northern and alpine ecosystems. - Terricolous lichen species' N content responds to both applied N concentration and load while applied N concentration has greatest effects on growth.

  9. Terricolous alpine lichens are sensitive to both load and concentration of applied nitrogen and have potential as bioindicators of nitrogen deposition

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Andrea J., E-mail: a.britton@macaulay.ac.u [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Fisher, Julia M. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom)

    2010-05-15

    The influence of applied nitrogen (N) concentration and load on thallus chemistry and growth of five terricolous alpine lichen species was investigated in a three-month N addition study. Thallus N content was influenced by both concentration and load; but the relative importance of these parameters varied between species. Growth was most affected by concentration. Thresholds for effects observed in this study support a low critical load for terricolous lichen communities (<7.5 kg N ha{sup -1} y{sup -1}) and suggest that concentrations of N currently encountered in UK cloudwater may have detrimental effects on the growth of sensitive species. The significance of N concentration effects on sensitive species also highlights the need to avoid artificially high concentrations when designing N addition experiments. Given the sensitivity of some species to extremely low loads and concentrations of N we suggest that terricolous lichens have potential as indicators of deposition and impact in northern and alpine ecosystems. - Terricolous lichen species' N content responds to both applied N concentration and load while applied N concentration has greatest effects on growth.

  10. Effects of noradrenaline on locomotor rhythm-generating networks in the isolated neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Kiehn, O; Sillar, K T; Kjaerulff, O

    1999-01-01

    locomotor-like rhythm, in which activity alternated between the left and right sides, and between rostral and caudal roots on the same side. As shown previously, stable locomotor activity could be induced by bath application of N-methyl-D-aspartate (NMDA; 4-8.5 microM) and/or serotonin (5-HT; 4-20 micro......M). NA modulated this activity by decreasing the cycle frequency and increasing the ventral root burst duration. These effects were dose dependent in the concentration range 1-5 microM. In contrast, at no concentration tested did NA have consistent effects on burst amplitudes or on the background...... activity of the ongoing rhythm. Moreover, NA did not obviously affect the left/right and rostrocaudal alternation of the NMDA/5-HT rhythm. The NMDA/5-HT locomotor rhythm sometimes displayed a time-dependent breakdown in coordination, ultimately resulting in tonic ventral root activity. However...

  11. EphA4 defines a class of excitatory locomotor-related interneurons

    DEFF Research Database (Denmark)

    Butt, S. J B; Lundfald, Line; Kiehn, Ole

    2005-01-01

    of these interneurons provide direct excitation to ipsilateral motor neurons as determined by spike-triggered averaging of the local ventral root DC trace. Our findings substantiate the role of EphA4-positive interneurons as significant components of the ipsilateral locomotor network and describe a group of putative...... of the role of these cells in the network. One such marker is the EphA4 axon guidance receptor. EphA4-null mice display an abnormal rabbit-like hopping gait that is thought to be the result of synchronization of the normally alternating, bilateral locomotor network via aberrant crossed connections....... In this study, we have performed whole-cell patch clamp on EphA4-positive interneurons in the flexor region (L2) of the locomotor network. We provide evidence that although EphA4 positive interneurons are not entirely a homogeneous population, most of them fire in a rhythmic manner. Moreover, a subset...

  12. Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

    Science.gov (United States)

    Hou, Fenxia; Xing, Caihong; Li, Bin; Cheng, Juan; Chen, Wei; Zhang, Man

    2015-01-01

    Allergic contact dermatitis (ACD) is a skin disease characterized by eczema and itching. A considerable proportion of chemicals induce ACD in humans. More than 10,000 substances should be tested for skin sensitization potential under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation. The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for sensitization testing by REACH. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. For both the LLNA and the LLNA:BrdU-ELISA, CBA/JN mouse is the preferred mouse strain recommended in the regulatory guidelines. However, the availability of CBA/JN mouse in China is only limited to a few animal suppliers, which makes the mouse difficult to obtain. BALB/c mouse, which is widely commercially available, is considered for alternative use but it can only be used in the assay after it has been evaluated by formal validation study. Thus, a validation study was conducted in our laboratory to determine if BALB/c mouse could also be used in the LLNA:BrdU-ELISA. Forty-three test substances including 32 LLNA sensitizers and 11 LLNA non-sensitizers, their vehicles and each concentration used were the same as that used in the formal validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. Female BALB/c mice of 8-10 weeks old were randomly allocated to groups (four mice per group). The test substance (25 μl) or the vehicle alone was applied to the dorsum of both ears daily for 3 consecutive days. A single intraperitoneal injection of 0.5 ml of BrdU (10mg/ml) solution was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, weighed and stored at -20°C until BrdU-ELISA was conducted. This validation study for the LLNA:BrdU-ELISA using BALB/c mouse correctly identified 30 of 31 sensitizers and 8 of 11 non-sensitizers. The accuracy, sensitivity, specificity, false positive rate, false negative rate

  13. Transmembrane potential polarization, calcium influx, and receptor conformational state modulate the sensitivity of the imidacloprid-insensitive neuronal insect nicotinic acetylcholine receptor to neonicotinoid insecticides.

    Science.gov (United States)

    Bodereau-Dubois, Béatrice; List, Olivier; Calas-List, Delphine; Marques, Olivier; Communal, Pierre-Yves; Thany, Steeve H; Lapied, Bruno

    2012-05-01

    Neonicotinoid insecticides act selectively on insect nicotinic acetylcholine receptors (nAChRs). Recent studies revealed that their efficiency was altered by the phosphorylation/dephosphorylation process and the intracellular signaling pathway involved in the regulation of nAChRs. Using whole-cell patch-clamp electrophysiology adapted for dissociated cockroach dorsal unpaired median (DUM) neurons, we demonstrated that intracellular factors involved in the regulation of nAChR function modulated neonicotinoid sensitivity. DUM neurons were known to express two α-bungarotoxin-insensitive nAChR subtypes: nAChR1 and nAChR2. Whereas nAChR1 was sensitive to imidacloprid, nAChR2 was insensitive to this insecticide. Here, we demonstrated that, like nicotine, acetamiprid and clothianidin, other types of neonicotinoid insecticides, acted as agonists on the nAChR2 subtype. Using acetamiprid, we revealed that both steady-state depolarization and hyperpolarization affected nAChR2 sensitivity. The measurement of the input membrane resistance indicated that change in the acetamiprid-induced agonist activity was related to the receptor conformational state. Using cadmium chloride, ω-conotoxin GVIA, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-acetamide (LOE 908), we found that inhibition of calcium influx through high voltage-activated calcium channels and transient receptor potential γ (TRPγ) activated by both depolarization and hyperpolarization increased nAChR2 sensitivity to acetamiprid. Finally, using N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7), forskolin, and cAMP, we demonstrated that adenylyl cyclase sensitive to the calcium/calmodulin complex regulated internal cAMP concentration, which in turn modulated TRPγ function and nAChR2 sensitivity to acetamiprid. Similar TRPγ-induced modulatory effects were also obtained when clothianidin was tested. These findings bring insights into the signaling pathway modulating

  14. Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin

    Directory of Open Access Journals (Sweden)

    Takahito Miyake

    2017-11-01

    Full Text Available Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1 is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD, which causes sensitization of TRPA1 to reactive oxygen species (ROS. Furthermore, PHD inhibition endows cold-insensitive human TRPA1 (hTRPA1 with ROS-dependent cold sensitivity. Since cysteine oxidation and proline hydroxylation regulate its activity, their association with oxaliplatin-induced TRPA1 activation and acquirement of cold sensitivity were investigated in the present study. A high concentration of oxaliplatin (1 mM induced outward-rectifier whole-cell currents and increased the intracellular Ca2+ concentration in hTRPA1-expressing HEK293 cells, but did not increase the probability of hTRPA1 channel opening in the inside-out configuration. Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala-expressing cells showed similar whole-cell currents and Ca2+ influx. By contrast, a lower concentration of oxaliplatin (100 μM did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower

  15. Cultured cells from a severe combined immunodeficient mouse have a slower than normal rate of repair of potentially lethal damage sensitive to hypertonic treatment

    International Nuclear Information System (INIS)

    Kimura, H.; Terado, T.; Ikebuchi, M.; Aoyama, T.; Komatsu, K.; Nozawa, A.

    1995-01-01

    The effects of hypertonic 0.5 M NaCl treatment after irradiation on the repair of DNA damage were examined in fibroblasts of the severe combined immunodeficient (scid) mouse. These cells are hypersensitive to ionizing radiation because of a deficiency in the repair of double-strand breaks. Hypertonic treatment caused radiosensitization due to a fixation of potentially lethal damage (PLD) in scid cells, demonstrating that scid cells normally repair PLD. To assess the kinetics of the repair of PLD, hypertonic treatment was delayed for various times after irradiation. Potentially lethal damage was repaired during these times in isotonic medium at 37 degrees C. It was found that the rate of repair of PLD was much slower in scid cells than in BALB/c 3T3 cells, which have a open-quotes wild-typeclose quotes level of radiosensitivity. This fact indicates that the scid mutation affects the type of repair of PLD that is sensitive to 0.5 M NaCl treatment. In scid hybrid cells containing fragments of human chromosome 8, which complements the radiosensitivity of the scid cells, the rate of repair was restored to a normal level. An enzyme encoded by a gene on chromosome 8 may also be connected with PLD which is sensitive to hypertonic treatment. 29 refs., 3 figs

  16. Locomotor muscle fatigue does not alter oxygen uptake kinetics during high-intensity exercise

    Directory of Open Access Journals (Sweden)

    James Hopker

    2016-10-01

    Full Text Available The slow component (VO2sc that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre fatigue condition or rest for 33 minutes (control condition according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-second maximal sprints at a fixed pedaling cadence of 90 rev·min-1. Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and VO2max determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue (P = 0.03, the VO2sc was not significantly different between the pre fatigue (464 ± 301 mL·min-1 and the control (556 ± 223 mL·min-1 condition (P = 0.50. Blood lactate response was not significantly different between conditions (P = 0.48 but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition (P < 0.01 suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the VO2 kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the VO2sc is strongly associated with locomotor muscle fatigue.

  17. Altered Patterns of Reflex Excitability, Balance, and Locomotion Following Spinal Cord Injury (SCI and Locomotor Training.

    Directory of Open Access Journals (Sweden)

    Prodip K Bose

    2012-07-01

    Full Text Available Spasticity is an important problem that complicates daily living in many individuals with SCI. While previous studies in human and animals revealed significant improvements in locomotor ability with treadmill locomotor training, it is not known to what extent locomotor training influences spasticity. In addition, it would be of considerable practical interest to know how the more ergonomically feasible cycle training compares with treadmill training as therapy to manage SCI-induced spasticity and to improve locomotor function. Our present studies were initiated to evaluate the influence of different types of locomotor training on measures of limb spasticity, gait, and reflex components that contribute to locomotion. For these studies, thirty animals received midthoracic SCI using the standard MASCIS protocol (10 g 2.5 cm weight drop. They were divided randomly into three equal groups: control (contused untrained, contused treadmill trained, and contused cycle trained. Velocity-dependent ankle torque was tested across a wide range of velocities (612 – 49 deg/sec to permit quantitation of tonic (low velocity and dynamic (high velocity contributions to lower limb spasticity. Treadmill and cycle training were started on post-injury day 8. By post-injury weeks 4 and 6, the untrained group revealed significant velocity-dependent ankle extensor spasticity, compared to pre-surgical control values. At these post-injury time points, spasticity was not observed in either of the two training groups. Instead, a significantly milder form of velocity dependent spasticity was detected at postcontusion week 8 through 12 in both treadmill and bicycle training groups at the four fastest ankle rotation velocities (350 - 612 deg/sec. Locomotor training using treadmill or bicycle also produced significant increase in the rate of recovery of limb placement measures (limb axis, base of support, and BBB and reflex rate depression, a quantitative assessment of

  18. Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise.

    Science.gov (United States)

    Hopker, James G; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M

    2016-01-01

    The [Formula: see text] slow component ([Formula: see text]) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min -1 . Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and [Formula: see text] determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue ( P = 0.03), the [Formula: see text] was not significantly different between the pre-fatigue (464 ± 301 mL·min -1 ) and the control (556 ± 223 mL·min -1 ) condition ( P = 0.50). Blood lactate response was not significantly different between conditions ( P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition ( P locomotor muscle fatigue does not significantly alter the [Formula: see text] kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the [Formula: see text] is strongly associated with locomotor muscle fatigue.

  19. Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

    Science.gov (United States)

    Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

    2017-06-15

    Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

    Science.gov (United States)

    Yamamoto, Dorothy J.; Nelson, Anna M.; Mandt, Bruce H.; Larson, Gaynor A.; Rorabaugh, Jacki M.; Ng, Christopher M.C.; Barcomb, Kelsey M.; Richards, Toni L.; Allen, Richard M.; Zahniser, Nancy R.

    2013-01-01

    Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine’s discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

  1. Asymmetric operation of the locomotor central pattern generator in the neonatal mouse spinal cord

    DEFF Research Database (Denmark)

    Endo, Toshiaki; Kiehn, Ole

    2008-01-01

    The rhythmic voltage oscillations in motor neurons (MNs) during locomotor movements reflect the operation of the pre-MN central pattern generator (CPG) network. Recordings from MNs can thus be used as a method to deduct the organization of CPGs. Here, we use continuous conductance measurements...... of locomotor CPG. The extracted excitatory and inhibitory synaptic conductances varied between 2 and 56% of the mean total conductance. Analysis of the phase tuning of the extracted synaptic conductances in flexor and extensor MNs in the rostral lumbar cord showed that the flexor-phase-related synaptic...

  2. Plasticity of locomotor sensorimotor interactions after peripheral and/or spinal lesions

    DEFF Research Database (Denmark)

    Rossignol, Serge; Barrière, Grégory; Frigon, Alain

    2008-01-01

    The present paper reviews aspects of locomotor sensorimotor interactions by focussing on work performed in spinal cats. We provide a brief overview of spinal locomotion and describe the effects of various types of sensory deprivations (e.g. rhizotomies, and lesions of muscle and cutaneous nerves......) to highlight the spinal neuroplasticity necessary for adapting to sensory loss. Recent work on plastic interactions between reflex pathways that could be responsible for such plasticity, in particular changes in proprioceptive and cutaneous pathways that occur during locomotor training of spinal cats...

  3. Glutamatergic mechanisms for speed control and network operation in the rodent locomotor CPG

    DEFF Research Database (Denmark)

    Talpalar, Adolfo E.; Kiehn, Ole

    2010-01-01

    in mammals have produced conflicting results regarding the necessity and role of the different ionotropic glutamate receptors (GluRs) in the CPG function. Here, we use electrophysiological and pharmacological techniques in the in vitro neonatal mouse lumbar spinal cord to investigate the role of a broad...... mechanisms acting at various network levels. AMPA and kainate receptors are necessary for generating the highest locomotor frequencies. For coordination, NMDARs are more important than non-NMDARs for conveying the rhythmic signal from the network to the motor neurons during long-lasting and steady locomotor...

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

    OpenAIRE

    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, th...

  5. Sleep pattern and locomotor activity are impaired by doxorubicin in non-tumor-bearing rats.

    Science.gov (United States)

    Lira, Fabio Santos; Esteves, Andrea Maculano; Pimentel, Gustavo Duarte; Rosa, José Cesar; Frank, Miriam Kannebley; Mariano, Melise Oliveira; Budni, Josiane; Quevedo, João; Santos, Ronaldo Vagner Dos; de Mello, Marco Túlio

    2016-01-01

    We sought explore the effects of doxorubicin on sleep patterns and locomotor activity. To investigate these effects, two groups were formed: a control group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control or DOXO groups. The sleep patterns were examined by polysomnographic recording and locomotor activity was evaluated in an open-field test. In the light period, the total sleep time and slow wave sleep were decreased, while the wake after sleep onset and arousal were increased in the DOXO group compared with the control group (plocomotor activity.

  6. Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance in a Discordant Sensory Environment

    Science.gov (United States)

    Temple, D. R.; De Dios, Y. E.; Layne, C. S.; Bloomberg, J. J.; Mulavara, A. P.

    2016-01-01

    Astronauts exposed to microgravity face sensorimotor challenges incurred when readapting to a gravitational environment. Sensorimotor Adaptability (SA) training has been proposed as a countermeasure to improve locomotor performance during re-adaptation, and it is suggested that the benefits of SA training may be further enhanced by improving detection of weak sensory signals via mechanisms such as stochastic resonance when a non-zero level of stochastic white noise based electrical stimulation is applied to the vestibular system (stochastic vestibular stimulation, SVS). The purpose of this study was to test the efficacy of using SVS to improve short-term adaptation in a sensory discordant environment during performance of a locomotor task.

  7. Effect of physical exercise prelabyrinthectomy on locomotor balance compensation in the squirrel monkey

    Science.gov (United States)

    Igarashi, M.; Ohashi, K.; Yoshihara, T.; MacDonald, S.

    1989-01-01

    This study examines the effectiveness of physical exercise, during a prepathology state, on locomotor balance compensation after subsequent unilateral labyrinthectomy in squirrel monkeys. An experimental group underwent 3 hr. of daily running exercise on a treadmill for 3 mo. prior to the surgery, whereas a control group was not exercised. Postoperatively, the locomotor balance function of both groups was tested for 3 mo. There was no significant difference in gait deviation counts in the acute phase of compensation. However, in the chronic compensation maintenance phase, the number of gait deviation counts was fewer in the exercise group, which showed significantly better performance stability.

  8. 1/N expansions for central potentials revisited in the light of hypervirial and Hellmann-Feynman theorems and the principle of minimal sensitivity

    International Nuclear Information System (INIS)

    Kwato Njock, M.G.; Bona, Z.; Nsangou, M.; Nana Engo, S.G.; Oumarou, B.

    1999-02-01

    The hypervirial and Hellmann-Feynman theorems are used in the methods of 1/N expansion to construct Rayleigh-Schroedinger perturbation expansion for bound-state energy eigenvalues of spherical symmetric potentials. A new iteration procedure of calculating correction terms of arbitrarily high orders is obtained for any kind of 1/N expansion. The recurrence formulas for three variants of the 1/N expansion are considered in this work, namely, the 1/n expansion, the shifted and unshifted 1/N expansions which are applied to the Gaussian and Patil potentials. As a result, their credibility could be reliably judged when account is taken of high order terms of the eigenenergies. It is also found that there is a distinct advantage in using the shifted 1/N expansion over the two other versions. However, the shifted 1/N expansion diverges for s states and in certain cases is not applicable as far as complicated potentials are concerned. In an effort to solve these problems we have incorporated the principle of minimal sensitivity in the shifted 1/N expansion as a first step toward extending the scope of applicability of that technique, and then we have tested the obtained approach to some unfavorable cases of the Patil and Hellmann potentials. The agreement between our numerical calculations and reference data is quite satisfactory. (author)

  9. Activity of Renshaw cells during locomotor-like rhythmic activity in the isolated spinal cord of neonatal mice

    DEFF Research Database (Denmark)

    Nishimaru, Hiroshi; Restrepo, Carlos E.; Kiehn, Ole

    2006-01-01

    % of the recorded RCs fired in-phase with the ipsilateral L2 flexor-related rhythm, whereas the rest fired in the extensor phase. Each population of RCs fired throughout the corresponding locomotor phase. All RCs received both excitatory and inhibitory synaptic inputs during the locomotor-like rhythmic activity...

  10. Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

    Science.gov (United States)

    Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

    2018-04-23

    Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

  11. Satisfaction and perceptions of long-term manual wheelchair users with a spinal cord injury upon completion of a locomotor training program with an overground robotic exoskeleton.

    Science.gov (United States)

    Gagnon, Dany H; Vermette, Martin; Duclos, Cyril; Aubertin-Leheudre, Mylène; Ahmed, Sara; Kairy, Dahlia

    2017-12-19

    The main objectives of this study were to quantify clients' satisfaction and perception upon completion of a locomotor training program with an overground robotic exoskeleton. A group of 14 wheelchair users with a spinal cord injury, who finished a 6-8-week locomotor training program with the robotic exoskeleton (18 training sessions), were invited to complete a web-based electronic questionnaire. This questionnaire encompassed 41 statements organized around seven key domains: overall satisfaction related to the training program, satisfaction related to the overground robotic exoskeleton, satisfaction related to the program attributes, perceived learnability, perceived health benefits and risks and perceived motivation to engage in physical activity. Each statement was rated using a visual analogue scale ranging from "0 = totally disagree" to "100 = completely agree". Overall, respondents unanimously considered themselves satisfied with the locomotor training program with the robotic exoskeleton (95.7 ± 0.7%) and provided positive feedback about the robotic exoskeleton itself (82.3 ± 6.9%), the attributes of the locomotor training program (84.5 ± 6.9%) and their ability to learn to perform sit-stand transfers and walk with the robotic exoskeleton (79.6 ± 17%). Respondents perceived some health benefits (67.9 ± 16.7%) and have reported no fear of developing secondary complications or of potential risk for themselves linked to the use of the robotic exoskeleton (16.7 ± 8.2%). At the end of the program, respondents felt motivated to engage in a regular physical activity program (91.3 ± 0.1%). This study provides new insights on satisfaction and perceptions of wheelchair users while also confirming the relevance to continue to improve such technologies, and informing the development of future clinical trials. Implications for Rehabilitation All long-term manual wheelchair users with a spinal cord injury who participated in the

  12. Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

    Science.gov (United States)

    Gallant, S; Welch, L; Martone, P; Shalev, U

    2017-06-15

    Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury.

    Science.gov (United States)

    Morrison, Sarah A; Lorenz, Douglas; Eskay, Carol P; Forrest, Gail F; Basso, D Michele

    2018-03-01

    To determine the impact of long-term, body weight-supported locomotor training after chronic, incomplete spinal cord injury (SCI), and to estimate the health care costs related to lost recovery potential and preventable secondary complications that may have occurred because of visit limits imposed by insurers. Prospective observational cohort with longitudinal follow-up. Eight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network (NRN). Individuals with motor incomplete chronic SCI (American Spinal Injury Association Impairment Scale C or D; N=69; 0.1-45y after SCI) who completed at least 120 NRN physical therapy sessions. Manually assisted locomotor training (LT) in a body weight-supported treadmill environment, overground standing and stepping activities, and community integration tasks. International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), Berg Balance Scale, Modified Functional Reach, 10-m walk test, and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6- to 12-month follow-up after discharge from therapy. Significant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement, and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6 to 12 months after treatment. Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20-session insurance limit can reduce rehospitalizations and long-term health costs. Copyright © 2018 American Congress of Rehabilitation Medicine

  14. Comparative locomotor costs of domestic dogs reveal energetic economy of wolf-like breeds.

    Science.gov (United States)

    Bryce, Caleb M; Williams, Terrie M

    2017-01-15

    The broad diversity in morphology and geographic distribution of the 35 free-ranging members of the family Canidae is only rivaled by that of the domesticated dog, Canis lupus familiaris. Considered to be among nature's most elite endurance athletes, both domestic and wild canids provide a unique opportunity to examine the variability in mammalian aerobic exercise performance and energy expenditure. To determine the potential effects of domestication and selective breeding on locomotor gait and economy in canids, we measured the kinematics and mass-specific metabolism of three large (>20 kg) dog breed groups (northern breeds, retrievers and hounds) of varying morphological and genomic relatedness to their shared progenitor, the gray wolf. By measuring all individuals moving in preferred steady-state gaits along a level transect and on a treadmill, we found distinct biomechanical, kinematic and energetic patterns for each breed group. While all groups exhibited reduced total cost of transport (COT) at faster speeds, the total COT and net COT during trotting and galloping were significantly lower for northern breed dogs (3.0 and 2.1 J kg -1  m -1 , respectively) relative to hound (4.2 and 3.4 J kg -1  m -1 , respectively) and retriever dogs (3.8 and 3.0 J kg -1  m -1 , respectively) of comparable mass. Similarly, northern breeds expended less energy per stride (3.5 J kg -1  stride -1 ) than hounds or retrievers (5.0 and 4.0 J kg -1  stride -1 , respectively). These results suggest that, in addition to their close genetic and morphological ties to gray wolves, northern breed dogs have retained highly cursorial kinematic and physiological traits that promote economical movement across the landscape. © 2017. Published by The Company of Biologists Ltd.

  15. Sensitive Detection of Plasmodium vivax Using a High-Throughput, Colourimetric Loop Mediated Isothermal Amplification (HtLAMP Platform: A Potential Novel Tool for Malaria Elimination.

    Directory of Open Access Journals (Sweden)

    Sumudu Britton

    2016-02-01

    Full Text Available Plasmodium vivax malaria has a wide geographic distribution and poses challenges to malaria elimination that are likely to be greater than those of P. falciparum. Diagnostic tools for P. vivax infection in non-reference laboratory settings are limited to microscopy and rapid diagnostic tests but these are unreliable at low parasitemia. The development and validation of a high-throughput and sensitive assay for P. vivax is a priority.A high-throughput LAMP assay targeting a P. vivax mitochondrial gene and deploying colorimetric detection in a 96-well plate format was developed and evaluated in the laboratory. Diagnostic accuracy was compared against microscopy, antigen detection tests and PCR and validated in samples from malaria patients and community controls in a district hospital setting in Sabah, Malaysia.The high throughput LAMP-P. vivax assay (HtLAMP-Pv performed with an estimated limit of detection of 1.4 parasites/ μL. Assay primers demonstrated cross-reactivity with P. knowlesi but not with other Plasmodium spp. Field testing of HtLAMP-Pv was conducted using 149 samples from symptomatic malaria patients (64 P. vivax, 17 P. falciparum, 56 P. knowlesi, 7 P. malariae, 1 mixed P. knowlesi/P. vivax, with 4 excluded. When compared against multiplex PCR, HtLAMP-Pv demonstrated a sensitivity for P. vivax of 95% (95% CI 87-99%; 61/64, and specificity of 100% (95% CI 86-100%; 25/25 when P. knowlesi samples were excluded. HtLAMP-Pv testing of 112 samples from asymptomatic community controls, 7 of which had submicroscopic P. vivax infections by PCR, showed a sensitivity of 71% (95% CI 29-96%; 5/7 and specificity of 93% (95% CI87-97%; 98/105.This novel HtLAMP-P. vivax assay has the potential to be a useful field applicable molecular diagnostic test for P. vivax infection in elimination settings.

  16. Radioecological sensitivity

    International Nuclear Information System (INIS)

    Howard, Brenda J.; Strand, Per; Assimakopoulos, Panayotis

    2003-01-01

    After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

  17. Signal sensitivity of alternating current potential drop measurement for crack detection of conductive substrate with tunable coating materials through finite element modeling

    International Nuclear Information System (INIS)

    Rao, Simha Sandeep; Zhao, Huijuan; Liu, Ming; Peng, Fei; Zhang, Bo

    2016-01-01

    We adopt a finite element numerical modeling approach to investigate the electromagnetic coupling effect of two parallel electric conductors with tunable electric conductivity σ and magnetic permeability μ . For two parallel conductors C and S ( μ C   ⋅  σ C   ≤  μ S   ⋅  σ S ), we find that the shape of current density profile of conductor S is dependent on the product of μ C   ⋅  σ C , while the magnitude is determined by the AC current frequency f . On the other hand, the frequency f affects not only the shape but also the magnitude of the current density profile of conductor C. We further adopt a coplanar model to investigate the signal sensitivity of alternating current potential drop (ACPD) measurement for both surface crack and inner crack detection. We find that with modified coating materials (lower electric conductivity and higher magnetic permeability, compared with the substrate material properties), the crack detection signal sensitivity can be greatly enhanced for both the cracks within the coating and at the coating/substrate interface, where cracks are most commonly encountered in real situations. (paper)

  18. Different role of TTX-sensitive voltage-gated sodium channel (NaV 1) subtypes in action potential initiation and conduction in vagal airway nociceptors.

    Science.gov (United States)

    Kollarik, M; Sun, H; Herbstsomer, R A; Ru, F; Kocmalova, M; Meeker, S N; Undem, B J

    2018-04-15

    The action potential initiation in the nerve terminals and its subsequent conduction along the axons of afferent nerves are not necessarily dependent on the same voltage-gated sodium channel (Na V 1) subunits. The action potential initiation in jugular C-fibres within airway tissues is not blocked by TTX; nonetheless, conduction of action potentials along the vagal axons of these nerves is often dependent on TTX-sensitive channels. This is not the case for nodose airway Aδ-fibres and C-fibres, where both action potential initiation and conduction is abolished by TTX or selective Na V 1.7 blockers. The difference between the initiation of action potentials within the airways vs. conduction along the axons should be considered when developing Na V 1 blocking drugs for topical application to the respiratory tract. The action potential (AP) initiation in the nerve terminals and its subsequent AP conduction along the axons do not necessarily depend on the same subtypes of voltage-gated sodium channels (Na V 1s). We evaluated the role of TTX-sensitive and TTX-resistant Na V 1s in vagal afferent nociceptor nerves derived from jugular and nodose ganglia innervating the respiratory system. Single cell RT-PCR was performed on vagal afferent neurons retrogradely labelled from the guinea pig trachea. Almost all of the jugular neurons expressed the TTX-sensitive channel Na V 1.7 along with TTX-resistant Na V 1.8 and Na V 1.9. Tracheal nodose neurons also expressed Na V 1.7 but, less frequently, Na V 1.8 and Na V 1.9. Na V 1.6 were expressed in ∼40% of the jugular and 25% of nodose tracheal neurons. Other Na V 1 α subunits were only rarely expressed. Single fibre recordings were made from the vagal nodose and jugular nerve fibres innervating the trachea or lung in the isolated perfused vagally-innervated preparations that allowed for selective drug delivery to the nerve terminal compartment (AP initiation) or to the desheathed vagus nerve (AP conduction). AP initiation in

  19. Optical fiber taste sensors using potential sensitive dye coatings. Makuden'i kanjusei shikisomaku wo mochiita hikari fiber mikaku sensor

    Energy Technology Data Exchange (ETDEWEB)

    Yamakawa, S.; Yamaguchi, A. (Toyama National College of Maritime Technology, Toyama (Japan))

    1992-12-20

    The present paper proposes a new taste recognition system using optical response patterns from multi-channel optical fiber sensors having potential sensitive dye coatings. It was found that the sensors give large changes in optical absorption spectra of the dyes when they are immersed in various taste solutions. Consequently, it was shown that the sensors can be used as a taste sensor. Six dyes, which give large changes in dye absorption, were selected from twenty dyes and used for six-channel optical fiber taste sensors array. The absorption spectra change data were processed by multiple discriminant analysis and neural networks using back-propagation algorithm. From the analytical results, it was demonstrated that salty (NaCl), bitter (quinidine), sweet (sucrose), sour (HCl), and umami (sodium glutamate) substances can be recognized from each other by using the optical taste sensor system. 11 refs., 8 figs., 2 tabs.

  20. Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions.

    Science.gov (United States)

    Hamezah, Hamizah Shahirah; Durani, Lina Wati; Ibrahim, Nor Faeizah; Yanagisawa, Daijiro; Kato, Tomoko; Shiino, Akihiko; Tanaka, Sachiko; Damanhuri, Hanafi Ahmad; Ngah, Wan Zurinah Wan; Tooyama, Ikuo

    2017-12-01

    Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1 H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age. Copyright © 2017. Published by Elsevier Inc.

  1. Human spinal locomotor control is based on flexibly organized burst generators

    OpenAIRE

    Danner, Simon M.; Hofstoetter, Ursula S.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-01-01

    Understanding the organisation of human spinal locomotor circuitry after severe CNS damage is essential for improving neurorehabilitation strategies. Danner et al. present evidence of flexibly organised burst-generating elements within the functionally isolated human lumbosacral spinal cord that generate rhythmic patterns in response to constant, repetitive epidural stimulation.

  2. MRT of the locomotor system. 4. rev. and enl. ed.; MRT des Bewegungsapparats

    Energy Technology Data Exchange (ETDEWEB)

    Vahlensieck, Martin [Praxisnetz Radiologie und Nuklearmedizin Bonn Bad Godesberg - RheinSieg, Bonn (Germany); Reiser, Maximilian (ed.) [Klinikum Grosshadern, Muenchen (Germany). Inst. fuer Klinische Radiologie

    2015-02-01

    The book on MRT of the locomotor system covers the following topics: relevant NMT imaging techniques, spinal cord, shoulder, elbows, wrist and fingers, hip region, knee, lower leg - ankle - foot, temporomandibular joint, skeletal muscles, bone marrow, bone and soft tissue tumors, osteoporosis, sacroiliac joint, jaw and periodontium.

  3. Gait quality is improved by locomotor training in individuals with SCI regardless of training approach

    NARCIS (Netherlands)

    Nooijen, C.F.J.; ter Hoeve, N.; Field-Fote, E.C.

    2009-01-01

    Background: While various body weight supported locomotor training (BWSLT) approaches are reported in the literature for individuals with spinal cord injury (SCI), none have evaluated outcomes in terms of gait quality. The purpose of this study was to compare changes in measures of gait quality

  4. Locomotor performance of cane toads differs between native-range and invasive populations.

    Science.gov (United States)

    Kosmala, Georgia; Christian, Keith; Brown, Gregory; Shine, Richard

    2017-07-01

    Invasive species provide a robust opportunity to evaluate how animals deal with novel environmental challenges. Shifts in locomotor performance-and thus the ability to disperse-(and especially, the degree to which it is constrained by thermal and hydric extremes) are of special importance, because they might affect the rate that an invader can spread. We studied cane toads ( Rhinella marina ) across a broad geographical range: two populations within the species' native range in Brazil, two invasive populations on the island of Hawai'i and eight invasive populations encompassing the eastern, western and southern limits of the toad invasion in Australia. A toad's locomotor performance on a circular raceway was strongly affected by both its temperature and its hydration state, but the nature and magnitude of those constraints differed across populations. In their native range, cane toads exhibited relatively low performance (even under optimal test conditions) and a rapid decrease in performance at lower temperatures and hydration levels. At the other extreme, performance was high in toads from southern Australia, and virtually unaffected by desiccation. Hawai'ian toads broadly resembled their Brazilian conspecifics, plausibly reflecting similar climatic conditions. The invasion of Australia has been accompanied by a dramatic enhancement in the toads' locomotor abilities, and (in some populations) by an ability to maintain locomotor performance even when the animal is cold and/or dehydrated. The geographical divergences in performance among cane toad populations graphically attest to the adaptability of invasive species in the face of novel abiotic challenges.

  5. Disruption of locomotor adaptation with repetitive transcranial magnetic stimulation over the motor cortex

    DEFF Research Database (Denmark)

    Choi, Julia Tsok Lam; Bouyer, Laurent J; Nielsen, Jens Bo

    2015-01-01

    Locomotor patterns are adapted on a trial-and-error basis to account for predictable dynamics. Once a walking pattern is adapted, the new calibration is stored and must be actively de-adapted. Here, we tested the hypothesis that storage of newly acquired ankle adaptation in walking is dependent...

  6. NeuroRecovery Network provides standardization of locomotor training for persons with incomplete spinal cord injury.

    Science.gov (United States)

    Morrison, Sarah A; Forrest, Gail F; VanHiel, Leslie R; Davé, Michele; D'Urso, Denise

    2012-09-01

    To illustrate the continuity of care afforded by a standardized locomotor training program across a multisite network setting within the Christopher and Dana Reeve Foundation NeuroRecovery Network (NRN). Single patient case study. Two geographically different hospital-based outpatient facilities. This case highlights a 25-year-old man diagnosed with C4 motor incomplete spinal cord injury with American Spinal Injury Association Impairment Scale grade D. Standardized locomotor training program 5 sessions per week for 1.5 hours per session, for a total of 100 treatment sessions, with 40 sessions at 1 center and 60 at another. Ten-meter walk test and 6-minute walk test were assessed at admission and discharge across both facilities. For each of the 100 treatment sessions percent body weight support, average, and maximum treadmill speed were evaluated. Locomotor endurance, as measured by the 6-minute walk test, and overground gait speed showed consistent improvement from admission to discharge. Throughout training, the patient decreased the need for body weight support and was able to tolerate faster treadmill speeds. Data indicate that the patient continued to improve on both treatment parameters and walking function. Standardization across the NRN centers provided a mechanism for delivering consistent and reproducible locomotor training programs across 2 facilities without disrupting training or recovery progression. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Slow Versus Fast Robot-Assisted Locomotor Training After Severe Stroke: A Randomized Controlled Trial.

    Science.gov (United States)

    Rodrigues, Thais Amanda; Goroso, Daniel Gustavo; Westgate, Philip M; Carrico, Cheryl; Batistella, Linamara R; Sawaki, Lumy

    2017-10-01

    Robot-assisted locomotor training on a bodyweight-supported treadmill is a rehabilitation intervention that compels repetitive practice of gait movements. Standard treadmill speed may elicit rhythmic movements generated primarily by spinal circuits. Slower-than-standard treadmill speed may elicit discrete movements, which are more complex than rhythmic movements and involve cortical areas. Compare effects of fast (i.e., rhythmic) versus slow (i.e., discrete) robot-assisted locomotor training on a bodyweight-supported treadmill in subjects with chronic, severe gait deficit after stroke. Subjects (N = 18) were randomized to receive 30 sessions (5 d/wk) of either fast or slow robot-assisted locomotor training on a bodyweight-supported treadmill in an inpatient setting. Functional ambulation category, time up and go, 6-min walk test, 10-m walk test, Berg Balance Scale, and Fugl-Meyer Assessment were administered at baseline and postintervention. The slow group had statistically significant improvement on functional ambulation category (first quartile-third quartile, P = 0.004), 6-min walk test (95% confidence interval [CI] = 1.8 to 49.0, P = 0.040), Berg Balance Scale (95% CI = 7.4 to 14.8, P locomotor training on a bodyweight-supported treadmill after severe stroke, slow training targeting discrete movement may yield greater benefit than fast training.

  8. Functional organization of V2a-related locomotor circuits in the rodent spinal cord

    DEFF Research Database (Denmark)

    Dougherty, Kimberly J.; Kiehn, Ole

    2010-01-01

    Studies of mammalian locomotion have been greatly facilitated by the use of the isolated rodent spinal cord preparation that retains the locomotor circuits needed to execute the movement. Physiological and molecular genetic experiments in this preparation have started to unravel the basic circuit...

  9. Self-Motion Perception during Locomotor Recalibration: More than Meets the Eye

    Science.gov (United States)

    Durgin, Frank H.; Pelah, Adar; Fox, Laura F.; Lewis, Jed; Kane, Rachel; Walley, Katherine A.

    2005-01-01

    Do locomotor after effects depend specifically on visual feedback? In 7 experiments, 116 college students were tested, with closed eyes, at stationary running or at walking to a previewed target after adaptation, with closed eyes, to treadmill locomotion. Subjects showed faster inadvertent drift during stationary running and increased distance…

  10. Temperature and Population Density Effects on Locomotor Activity of Musca domestica (Diptera: Muscidae)

    DEFF Research Database (Denmark)

    Schou, T. M.; Faurby, S.; Kjærsgaard, A.

    2013-01-01

    The behavior of ectotherm organisms is affected by both abiotic and biotic factors. However, a limited number of studies have investigated the synergistic effects on behavioral traits. This study examined the effect of temperature and density on locomotor activity of Musca domestica (L.). Locomot...

  11. The morphological development of the locomotor and cardiac muscles of the migratory barnacle goose (Branta leucopsis)

    NARCIS (Netherlands)

    Bishop, CM; Butler, PJ; ElHaj, AJ; Egginton, S; Loonen, MJJE

    The masses of the locomotor and cardiac muscles of wild barnacle goose goslings, from a migratory population, were examined systematically during development and their values compared to those of pre-migratory geese. Pre-flight development was typified by approximately linear increases of body, leg,

  12. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus)

    Science.gov (United States)

    Walaszczyk, Erin J.; Johnson, Nicholas S.; Steibel, Juan Pedro; Li, Weiming

    2013-01-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p reproductive synchrony of mature adults, thus increasing reproductive success in this species.

  13. Drugs that Target Dopamine Receptors: Changes in Locomotor Activity in Larval Zebrafish

    Science.gov (United States)

    As part of an effort at the US Environmental Protection Agency to develop a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae. This includes assessing the acute effects of drugs known...

  14. Efficacy of Static Magnetic Field for Locomotor Activity of Experimental Osteopenia

    Directory of Open Access Journals (Sweden)

    Norimasa Taniguchi

    2007-01-01

    Full Text Available In order to examine the effectiveness of applying a static magnetic field (SMF for increasing bone mineral density (BMD, we assessed the degree of osteopenia by dual-energy X-ray absorptiometry (DEXA, the metabolism measuring system, and histological examination of bone tissue in an ovariectomized (OVX rat model. Thirty-six female Wistar rats (8 weeks old, 160–180 g were divided into three groups. The rats in the OVX-M group were exposed to SMF for 12 weeks after ovariectomy. The ovariectomized rats in the OVX-D group were not exposed to SMF as a control. The rats in the normal group received neither ovariectomy nor exposure to SMF. Twelve-week exposure to SMF in the OVX-M group inhibited the reduction in BMD that was observed in the OVX-D group. Moreover, in the OVX rats, before exposure to SMF, there was no clear difference in the level of locomotor activity between the active and resting phases, and the pattern of locomotor activity was irregular. After exposure of OVX rats to SMF, the pattern of locomotor activity became diphasic with clear active and resting phases, as was observed in the normal group. In the OVX-M group, the continuity of the trabecular bone was maintained more favorably and bone mass was higher than the respective parameters in the OVX-D group. These results demonstrate that exposure to SMF increased the level of locomotor activity in OVX rats, thereby increasing BMD.

  15. Fractional-Order Information in the Visual Control of Lateral Locomotor Interception

    NARCIS (Netherlands)

    Bootsma, Reinoud J.; Ledouit, Simon; Casanova, Remy; Zaal, Frank T. J. M.

    Previous work on locomotor interception of a target moving in the transverse plane has suggested that interception is achieved by maintaining the target's bearing angle (often inadvertently confused and/or confounded with the target heading angle) at a constant value. However, dynamics-based model

  16. Plateau properties in mammalian spinal interneurons during transmitter-induced locomotor activity

    DEFF Research Database (Denmark)

    Kiehn, O.; Johnson, B. R.; Raastad, M.

    1996-01-01

    We examined the organization of spinal networks controlling locomotion in the isolated spinal cord of the neonatal rat, and in this study we provide the first demonstration of plateau and bursting mechanisms in mammalian interneurons that show locomotor-related activity. Using tight-seal whole...

  17. Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

    NARCIS (Netherlands)

    DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

    2016-01-01

    Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral

  18. Zebrafish Locomotor Responses Predict Irritant Potential of Smoke Particulate Matter from Five Biomass Fuels

    Science.gov (United States)

    Over the past few decades, the drying and warming trends of global climate change have increased wildland fire (WF) season length, as well as geographic area impacted. Consequently, exposures to WF fine particulate matter (PM2.5; aerodynamic diameter <2.5 µm) are likely ...

  19. Why pitch sensitivity matters: Event-related potential evidence of metric and syntactic violation detection among Spanish late learners of German.

    Directory of Open Access Journals (Sweden)

    Maren eSchmidt-Kassow

    2011-06-01

    Full Text Available Event-related potential (ERP data in monolingual German speakers have shown that sentential metric expectancy violations elicit a biphasic ERP pattern consisting of an anterior negativity and a posterior positivity (P600. This pattern is comparable to that elicited by syntactic violations. However, proficient French late learners of German do not detect violations of metric expectancy in German. They also show qualitatively and quantitatively different ERP responses to metric and syntactic violations. We followed up the questions whether (1 latter evidence results from a potential pitch cue insensitivity in speech segmentation in French speakers, or (2 if the result is founded in rhythmic language differences. Therefore, we tested Spanish late learners of German, as Spanish, contrary to French, uses pitch as a segmentation cue even though the basic segmentation unit is the same in French and Spanish (i.e., the syllable. We report ERP responses showing that Spanish L2 learners are sensitive to syntactic as well as metric violations in German sentences independent of attention to task in a P600 response. Overall, the behavioral performance resembles that of German native speakers. The current data suggest that Spanish L2 learners are able to extract metric units (trochee in their L2 (German even though their basic segmentation unit in Spanish is the syllable. In addition Spanish in contrast to French L2 learners of German are sensitive to syntactic violations indicating a tight link between syntactic and metric competence. This finding emphasizes the relevant role of metric cues not only in L2 prosodic but also in syntactic processing.

  20. A single exercise bout and locomotor learning after stroke: physiological, behavioural, and computational outcomes.

    Science.gov (United States)

    Charalambous, Charalambos C; Alcantara, Carolina C; French, Margaret A; Li, Xin; Matt, Kathleen S; Kim, Hyosub E; Morton, Susanne M; Reisman, Darcy S

    2018-05-15

    Previous work demonstrated an effect of a single high-intensity exercise bout coupled with motor practice on the retention of a newly acquired skilled arm movement, in both neurologically intact and impaired adults. In the present study, using behavioural and computational analyses we demonstrated that a single exercise bout, regardless of its intensity and timing, did not increase the retention of a novel locomotor task after stroke. Considering both present and previous work, we postulate that the benefits of exercise effect may depend on the type of motor learning (e.g. skill learning, sensorimotor adaptation) and/or task (e.g. arm accuracy-tracking task, walking). Acute high-intensity exercise coupled with motor practice improves the retention of motor learning in neurologically intact adults. However, whether exercise could improve the retention of locomotor learning after stroke is still unknown. Here, we investigated the effect of exercise intensity and timing on the retention of a novel locomotor learning task (i.e. split-belt treadmill walking) after stroke. Thirty-seven people post stroke participated in two sessions, 24 h apart, and were allocated to active control (CON), treadmill walking (TMW), or total body exercise on a cycle ergometer (TBE). In session 1, all groups exercised for a short bout (∼5 min) at low (CON) or high (TMW and TBE) intensity and before (CON and TMW) or after (TBE) the locomotor learning task. In both sessions, the locomotor learning task was to walk on a split-belt treadmill in a 2:1 speed ratio (100% and 50% fast-comfortable walking speed) for 15 min. To test the effect of exercise on 24 h retention, we applied behavioural and computational analyses. Behavioural data showed that neither high-intensity group showed greater 24 h retention compared to CON, and computational data showed that 24 h retention was attributable to a slow learning process for sensorimotor adaptation. Our findings demonstrated that acute exercise

  1. Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.

    Science.gov (United States)

    Dominelli, Paolo B; Archiza, Bruno; Ramsook, Andrew H; Mitchell, Reid A; Peters, Carli M; Molgat-Seon, Yannick; Henderson, William R; Koehle, Michael S; Boushel, Robert; Sheel, A William

    2017-11-01

    What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the

  2. Oxidized trilinoleate and tridocosahexaenoate induce pica behavior and change locomotor activity.

    Science.gov (United States)

    Kitamura, Fuki; Watanabe, Hiroyuki; Umeno, Aya; Yoshida, Yasukazu; Kurata, Kenji; Gotoh, Naohiro

    2013-01-01

    Pica behavior, a behavior that is characterized by eating a nonfood material such as kaolin and relates to the degree of discomfort in animals, and the variations of locomotor activity of rats after eating deteriorated fat and oil extracted from instant noodles were examined in our previous study. The result shows that oxidized fat and oil with at least 100 meq/kg in peroxide value (PV) increase pica behavior and decrease locomotor activity. In the present study, the same two behaviors were measured using autoxidized trilinoleate (tri-LA) and tridocosahexaenoate (tri-DHA) as a model of vegetable and fish oil, respectively, to compare fatty acid differences against the induction of two behaviors. The oxidized levels of tri-LA and tri-DHA were analyzed with PV and p-anisidine value (AnV), the method to analyze secondary oxidized products. The oxidation levels of respective triacylglycerol (TAG) samples were carefully adjusted to make them having almost the same PV and AnV. As the results, 600 or more meq/kg in PV of both TAGs significantly increased the consumption of kaolin pellets compared to the control group. Furthermore, 300 or more meq/kg in PV of tri-LA and 200 or more meq/kg in PV of tri-DHA demonstrated significant decrease in locomotor activity compared to control group. These results would indicate that the oxidized TAG having the same PV and/or AnV would induce the same type of pica behavior and locomotor activity. Furthermore, that the structure of oxidized products might not be important and the amount of hydroperoxide group and/or aldehyde group in deteriorated fats and oils might affect the pica behavior and locomotor activity were thought.

  3. The effects of long-term dopaminergic treatment on locomotor behavior in rats.

    Science.gov (United States)

    Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

    2014-12-01

    Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Au