Sample records for inhibitory avoidance retention

  1. The inhibitory avoidance discrimination task to investigate accuracy of memory.

    PubMed

    Atucha, Erika; Roozendaal, Benno

    2015-01-01

    The present study was aimed at developing a new inhibitory avoidance task, based on training and/or testing rats in multiple contexts, to investigate accuracy of memory. In the first experiment, male Sprague-Dawley rats were given footshock in an inhibitory avoidance apparatus and, 48 h later, retention latencies of each rat were assessed in the training apparatus (Shock box) as well as in a novel, contextually modified, apparatus. Retention latencies in the Shock box were significantly longer than those in the Novel box, indicating accurate memory of the training context. When the noradrenergic stimulant yohimbine (0.3 mg/kg, sc) was administered after the training, 48-h retention latencies in the Shock box, but not Novel box, were increased, indicating that the noradrenergic activation enhanced memory of the training experience without reducing memory accuracy. In the second experiment, rats were trained on an inhibitory avoidance discrimination task: They were first trained in an inhibitory avoidance apparatus without footshock (Non-Shock box), followed 1 min later by footshock training in a contextually modified apparatus (Shock box). Forty-eight-hour retention latencies in the Shock and Non-Shock boxes did not differ from each other but were both significantly longer than those in a Novel box, indicating that rats remembered the two training contexts but did not have episodic-like memory of the association of footshock with the correct training context. When the interval between the two training episodes was increased to 2 min, rats showed accurate memory of the association of footshock with the training context. Yohimbine administered after the training also enhanced rats' ability to remember in which training context they had received actual footshock. These findings indicate that the inhibitory avoidance discrimination task is a novel variant of the well-established inhibitory avoidance task suitable to investigate accuracy of memory.

  2. Gastrodia elata Bl. Attenuated learning deficits induced by forced-swimming stress in the inhibitory avoidance task and Morris water maze.

    PubMed

    Chen, Pei-Ju; Liang, Keng-Chen; Lin, Hui-Chen; Hsieh, Ching-Liang; Su, Kuan-Pin; Hung, Mei-Chu; Sheen, Lee-Yan

    2011-06-01

    This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

  3. Post-Retrieval Effects of ICV Infusions of Hemicholinium in Mice Are Dependent on the Age of the Original Memory

    ERIC Educational Resources Information Center

    Boccia, Mariano M.; Blake, Mariano G.; Acosta, Gabriela B.; Baratti, Carlos M.

    2006-01-01

    CF-1 male mice were trained in an inhibitory avoidance task using a high footshock (1,2 mA, 50 Hz, 1 sec) in order to reduce the influence of extinction on retention performance. At 2, 7, 14, or 30 d after training, the first retention test was performed and hemicholinium (HC-3, 1.0 microgram/mice), a specific inhibitor of high-affinity choline…

  4. Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans.

    PubMed

    Grillon, Christian; Cordova, Jeremy; Morgan, Charles Andrew; Charney, Dennis S; Davis, Michael

    2004-09-01

    Beta-adrenergic receptors are involved in the consolidation of emotional memories. Yet, a number of studies using Pavlovian cued fear conditioning have been unable to demonstrate an effect of beta-adrenergic blockade on acquisition or retention of fear conditioning. Evidence for the involvement of beta-adrenergic receptors in emotional memories comes mostly from studies using fear inhibitory avoidance in rodents. It is possible that fear inhibitory avoidance is more akin to contextual conditioning than to cued fear conditioning, suggesting that context conditioning may be disrupted by beta-adrenergic blockade. This study investigated the effects of the beta-adrenergic blocker propranolol on cued and contextual fear conditioning in humans. Subjects were given either placebo (n=15) or 40 mg propranolol (n=15) prior to differential cued conditioning. A week later, they were tested for retention of context and cued fear conditioning using physiological (startle reflex and electrodermal activity) and subjective measures of emotional arousal. The results were consistent with the hypothesis. The skin conductance level (SCL) and the subjective measure of arousal suggested reduced emotional arousal upon returning to the conditioning context in the propranolol group, compared to the placebo group. The acquisition and retention of cued fear conditioning were not affected by propranolol. These results suggest that beta-adrenergic receptors are involved in contextual fear conditioning.

  5. Sildenafil, a selective phosphodiesterase type 5 inhibitor, enhances memory reconsolidation of an inhibitory avoidance task in mice.

    PubMed

    Boccia, M M; Blake, M G; Krawczyk, M C; Baratti, C M

    2011-07-07

    Intracellular levels of the second messengers cAMP and cGMP are maintained through a balance between production, carried out by adenyl cyclase (AC) and guanylyl cyclase (GC), and degradation, carried out by phosphodiesterases (PDEs). Recently, PDEs have gained increased attention as potential new targets for cognition enhancement, with particular reference to phosphodiesterase type 5 (PDE5A). It is accepted that once consolidation is completed memory becomes permanent, but it has also been suggested that reactivation (memory retrieval) of the original memory makes it sensitive to the same treatments that affect memory consolidation when given after training. This new period of sensitivity coined the term reconsolidation. Sildenafil (1, 3, and 10mg/kg, ip), a cGMP-PDE5 inhibitor, facilitated retention performance of a one-trial step-through inhibitory avoidance task, when administered to CF-1 male mice immediately after retrieval. The effects of sildenafil (1mg/kg, ip) were time-dependent, long-lasting and inversely correlated with memory age. The administration of sildenafil (1mg/kg, ip) 30 min prior to the 2nd retention test did not affect retention of mice given post-retrieval injections of either vehicle or sildenafil (1mg/kg, ip). Finally, an enhancement of retention was also observed in CF-1 female mice receiving sildenafil (1mg/kg, ip) immediately, but not 180 min after retrieval. In the present paper we reported for the first time that systemic administration of sildenafil after memory reactivation enhances retention performance of the original learning. Our results indirectly point out cGMP, a component of the NO/cGMP/PKG pathway, as a necessary factor for memory reconsolidation. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. [Beta]-Adrenergic Receptors in the Insular Cortex are Differentially Involved in Aversive vs. Incidental Context Memory Formation

    ERIC Educational Resources Information Center

    Miranda, Maria Isabel; Sabath, Elizabeth; Nunez-Jaramillo, Luis; Puron-Sierra, Liliana

    2011-01-01

    The goal of this research was to determine the effects of [beta]-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the [beta]-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition…

  7. Scopolamine- and diazepam-induced amnesia are blocked by systemic and intraseptal administration of substance P and choline chloride.

    PubMed

    Costa, Joseane Carvalho; Costa, Kauê Machado; do Nascimento, José Luiz Martins

    2010-09-01

    Systemic (IP) and/or intraseptal (IS) administration of scopolamine (SCP) and diazepam (DZP) induce amnesia, whereas IP injection of the neuropeptide substance P (SP) and choline chloride (ChCl) produce memory facilitation. The septohippocampal cholinergic system has been pointed out as a possible site of SCP and DZP-induced amnesia as well as for the mnemonic effects induced by SP and ChCl. We performed a series of experiments in order to investigate the interactions between cholinergic and GABA/benzodiazepine (GABA/BZD) systems with the SPergic system on inhibitory avoidance retention. Male Wistar rats were trained and tested in a step-down inhibitory avoidance task (1.0 mA footshock). Animals received, pre-training, IP (1.0 mg/kg) or IS (1.0 nM/0.5 microl) injection of DZP, SCP (SCP; 1.0 mg/kg - IP or 0.5 microM/0.5 microl--IS) or vehicle (VEH). Immediately after training they received an IP or IS injections of SP 1-11 (50 microg/kg--IP or 1.0 nM/0.5 microl--IS), SP 1-7 (167 microg/kg--IP or 1.0 nM/0.5 microl--IS), ChCl (20 mg/kg--IP or 0.3 microM/0.5 microl--IS) or VEH. Rats pretreated with SCP and DZP showed amnesia. Post-trial treatments with SP 1-11, SP 1-7 or ChCl blocked the amnesic effects of SCP and DZP. These findings suggest an interaction between SPergic and cholinergic mechanisms with GABAergic systems in the modulation of inhibitory avoidance retention and that the effects of these treatments are mediated, at least in part, by interactions in the septohippocampal pathway. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Role of D2 dopamine receptors of the ventral pallidum in inhibitory avoidance learning.

    PubMed

    Lénárd, László; Ollmann, Tamás; László, Kristóf; Kovács, Anita; Gálosi, Rita; Kállai, Veronika; Attila, Tóth; Kertes, Erika; Zagoracz, Olga; Karádi, Zoltán; Péczely, László

    2017-03-15

    In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm. Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors. Control animals received saline. In a supplementary experiment, it was also investigated whether application of the same conditioning method leads to the formation of short-term memory in the experimental animals. In the experiment with the D2 DA receptor agonist, only the 0.1μg quinpirole increased significantly the step-through latency during the test trials: retention was significant compared to the controls even 2 weeks after conditioning. The D2 DA receptor antagonist sulpiride pretreatment proved that the effect was due to the agonist induced activation of the D2 DA receptors of the VP. The supplementary experiment demonstrated that short-term memory is formed after conditioning in the experimental animals, supporting that the agonist enhanced memory consolidation in the first two experiments. Our results show that the activation of the D2 DA receptors in the VP facilitates memory consolidation as well as memory-retention in inhibitory avoidance paradigm. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Post-training reversible disconnection of the ventral hippocampal-basolateral amygdaloid circuits impairs consolidation of inhibitory avoidance memory in rats.

    PubMed

    Wang, Gong-Wu; Liu, Jian; Wang, Xiao-Qin

    2017-11-01

    The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH-BLA circuit in IA memory consolidation. Male Wistar rats with implanted guide cannulae were trained with a one-trial IA task, then received immediate intracerebral injections of muscimol or saline, and were tested 24 h later. Muscimol injection into the bilateral BLA, or the unilateral VH and contralateral BLA, but not the unilateral VH and ipsilateral BLA, significantly decreased the retention latencies (versus saline treatment). The results suggest that the VH-BLA circuit could be an important circuit to modulate consolidation of IA memory in rats. © 2017 Wang et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test.

    PubMed

    Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S

    2015-02-01

    The forced swimming test (FST) remains one of the most used tools for screening antidepressants in rodent models. Nonetheless, the nature of immobility, its main behavioral measure, is still a matter of debate. The present study took advantage of our recent finding that mice of the inbred DBA/2J strain require a functioning left dorsolateral striatum (DLS) to consolidate long-term memory of FST to test whether immobility is the outcome of stress-related learning. Infusion of the GABA-A agonist muscimol in the left DLS immediately after a single experience of FST prevented and infusion in the left or the right amygdala impaired recall of the acquired levels of immobility in a probe test performed 24h later. Post-training left DLS infusion of muscimol, at a dose capable of preventing retention of FST-induced immobility, did not influence 24h retention of inhibitory avoidance training or of the escape response acquired in a water T-maze. However, this same treatment prevented 24h retention of the extinction training of the consolidated escape response. These results indicate that a left DLS-centered memory system selectively mediates memory consolidation of FST and of escape extinction and support the hypothesis that immobility is the result of extinction-like inhibitory learning involving all available escape responses due to the inescapable/unavoidable nature of FST experience. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Role of state-dependent learning in the cognitive effects of caffeine in mice.

    PubMed

    Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2013-08-01

    Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.

  12. Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory With Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

    PubMed Central

    Miranda, María I.; McGaugh, James L.

    2004-01-01

    There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 μg oxotremorine and 1.25 μg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of β-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation. PMID:15169861

  13. Aniracetam reverses memory impairment in rats.

    PubMed

    Martin, J R; Moreau, J L; Jenck, F

    1995-02-01

    The pyrrolidinone derivative aniracetam given orally immediately after acquisition of an inhibitory avoidance response reproducibly ameliorated scopolamine-induced amnesia in female rats in an extensive series of test sessions conducted over a 1-year period. In a dose-response experiment it was demonstrated that 50 mg kg-1 was the lowest oral dose of aniracetam to significantly ameliorate scopolamine-induced amnesia. Combined results from these numerous test sessions demonstrated that 50 mg kg-1 aniracetam administered to scopolamine-treated rats resulted in 53% of the animals exhibiting correct passive avoidance responding in the retention evaluation versus 9% of the scopolamine-treated rats given vehicle (in comparison, 64% of the rats injected with vehicle rather than scopolamine in this experimental situation exhibited correct responding in the retention test). There was minimal variation in this pattern of results over the successive 1-month blocks constituting the complete experimental period. Thus, the nootropic compound aniracetam replicably exhibited memory enhancing effects in this animal model of reduced cholinergic function.

  14. Effects of oxotremorine and physostigmine on the inhibitory avoidance impairment produced by amitriptyline in male and female mice.

    PubMed

    Monleón, Santiago; Urquiza, Adoración; Vinader-Caerols, Concepción; Parra, Andrés

    2009-12-28

    We have previously observed that amitriptyline and other antidepressants produce impairing effects on inhibitory avoidance (also called passive avoidance) in mice of both sexes. In the present study we investigated the involvement of the cholinergic system in the inhibitory avoidance impairment produced by acute amitriptyline in male and female CD1 mice. For this purpose, the effects on said task of acute i.p. administration of several doses of amitriptyline, either alone or in combination with the cholinergic agonists oxotremorine and physostigmine, were evaluated. Pre-training administration of 5, 7.5, 10 or 15 mg/kg of amitriptyline produced a significant impairment of inhibitory avoidance in both males and females. When oxotremorine (0.05 or 0.1 mg/kg) was co-administered with amitriptyline, the antidepressant's impairing effect was partially counteracted, although inhibitory avoidance learning was not significant. Physostigmine (0.15, 0.3 or 0.6 mg/kg) counteracted the impairment produced by amitriptyline, as mice treated with both drugs exhibited inhibitory avoidance learning. These results show that the inhibitory avoidance impairment produced by amitriptyline in male and female mice is mediated, at least partially, by the cholinergic system.

  15. Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats

    PubMed Central

    Bernabeu, Ramon; Bevilaqua, Lia; Ardenghi, Patricia; Bromberg, Elke; Schmitz, Paulo; Bianchin, Marino; Izquierdo, Ivan; Medina, Jorge H.

    1997-01-01

    cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation. Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393 (7.5 μg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 μg/side), a D1/D5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training. Intrahippocampal infusion of 8Br-cAMP (1.25 μg/side), or forskolin (0.5 μg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training. KT5720 (0.5 μg/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining. Rats submitted to the avoidance task showed learning-specific increases in hippocampal 3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus. PMID:9192688

  16. Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy.

    PubMed

    Dubrovina, N I; Zinov'ev, D R; Zinov'eva, D V; Kulikov, A V

    2009-06-01

    This report presents results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in ASC mice, which were bred for a high level of predisposition to catalepsy, and in CBA and AKR mice. The following findings were obtained: 1) impairments to the extinction of the memory of fear represent an important symptom of depression in ASC mice; 2) extinction is delayed in CBA mice; and 3) new inhibitory learning occurs quickly in AKR mice. Prolonged retention of the fear memory in ASC mice appears to be related to increased anxiety on prolonged testing without a punishment. The deficit of inhibition of the fear reaction in ASC mice allows this strain to be regarded as a genetic model of depression.

  17. CB1 receptors in the formation of the different phases of memory-related processes in the inhibitory avoidance test in mice.

    PubMed

    Kruk-Slomka, Marta; Biala, Grażyna

    2016-03-15

    The endocannabinoid system, through the cannabinoid type 1 (CB1) and 2 (CB2) receptors modulates many physiological functions, including different aspects of memory-related processes. The aim of the present experiments was to explore the role of the endocannabinoid system, through CB1 receptors in the different stages of short-term (acquisition, retention and retrieval) and long-term (acquisition, consolidation and retrieval) memory-related responses, using the inhibitory avoidance (IA) test in mice. Our results revealed that an acute injection of oleamide (10 and 20mg/kg), a CB1 receptor agonist, impairs the short-term or/and long-term acquisition, retention/consolidation, retrieval memory and learning processes in the IA test in mice. In turn, in this test an acute injection of AM 251 (1 and 3mg/kg), a CB1 receptor antagonist, improves the short-term or/and long-term memory stages, described above. Moreover, this memory impairment induced by effective dose of oleamide (20mg/kg) is reversed by non-effective dose of AM 251 (0.25mg/kg) in the IA task, which proves the selectivity of oleamide to CB1 receptors and confirms that the CB1 receptor-related mechanism is one of the possible mechanisms, responsible for memory and learning responses. Obtained results provide clear evidence that the endocannabinoid system, through CB1 receptors, participates in the different stages of short- and long-term memory-related behavior. This knowledge may open in the future new possibilities for the development of CB-based therapies, especially for memory impairment human disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Facilitation of learning and modulation of frontal cortex acetylcholine by ventral pallidal injection of heparin glucosaminoglycan.

    PubMed

    De Souza Silva, M A; Jezek, K; Weth, K; Müller, H W; Huston, J P; Brandao, M L; Hasenöhrl, R U

    2002-01-01

    We examined the effects of heparin on learning and frontal cortex acetylcholine parameters following injection of the glucosaminoglycan into the ventral pallidum. In Experiment 1, possible mnemoactive effects of intrapallidal heparin injection were assessed. Rats with chronically implanted cannulae were administered heparin (0.1, 1.0, 10 ng) or vehicle (0.5 microl) and were tested on a one-trial step-through avoidance task. Two retention tests were carried out in each animal, one at 1.5 h after training to measure short-term memory and another at 24 h to measure long-term memory. Post-trial intrapallidal injection of 1.0 ng heparin improved both short- and long-term retention of the task, whereas the lower and the higher dose of the glucosaminoglycan had no effect. When the effective dose of heparin was injected 5 h, rather than immediately after training, it no longer facilitated long-term retention of the conditioned avoidance response. In Experiment 2, the effects of ventral pallidal heparin injection on frontal cortex acetylcholine and choline concentrations were investigated with in vivo microdialysis in anaesthetized rats. Heparin, administered in the dose of 1.0 ng, which was effective in facilitating avoidance performance, produced a delayed increase in cortical acetylcholine levels ipsi- and contralaterally to the side of intrabasalis injection, resembling the known neurochemical effects obtained for another glycosaminoglycan, chondroitin sulfate, which recently was shown to facilitate inhibitory avoidance learning and to increase frontal cortex acetylcholine. The present findings indicate that heparin, like other extracellular matrix proteoglycans, can exert beneficial effects on memory and strengthen the presumptive relationship between such promnestic effects of proteoglycans and basal forebrain cholinergic mechanisms. The data are discussed with respect to the presumed roles of matrix molecules in extrasynaptic volume transmission and in the 'cross-talk' between synapses.

  19. Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex

    PubMed Central

    Bravo-Rivera, Christian; Rodriguez-Romaguera, Jose; Pagan-Rivera, Pablo A; Burgos-Robles, Anthony; Roman-Ortiz, Ciorana; Quirk, Gregory J

    2018-01-01

    Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed avoidance. Surprisingly, optogenetic silencing of PL glutamatergic neurons did not delay avoidance. Consistent with this, inhibitory but not excitatory responses of rostral PL neurons were associated with avoidance training. To test the importance of these inhibitory responses, we optogenetically stimulated PL neurons to counteract the tone-elicited reduction in firing rate. Photoactivation of rostral (but not caudal) PL neurons at 4 Hz impaired avoidance. These findings suggest that inhibitory responses of rostral PL neurons signal the avoidability of a potential threat and underscore the importance of designing behavioral optogenetic studies based on neuronal firing responses. PMID:29851381

  20. Altered behavior in experimental cortical dysplasia.

    PubMed

    Zhou, Fu-Wen; Rani, Asha; Martinez-Diaz, Hildabelis; Foster, Thomas C; Roper, Steven N

    2011-12-01

    Developmental delay and cognitive impairment are common comorbidities in people with epilepsy associated with malformations of cortical development (MCDs). We studied cognition and behavior in an animal model of diffuse cortical dysplasia (CD), in utero irradiation, using a battery of behavioral tests for neuromuscular and cognitive function. Fetal rats were exposed to 2.25 Gy external radiation on embryonic day 17 (E17). At 1 month of age they were tested using an open field task, a grip strength task, a grid walk task, inhibitory avoidance, an object recognition task, and the Morris water maze task. Rats with CD showed reduced nonlocomotor activity in the open field task and impaired motor coordination for grid walking but normal grip strength. They showed a reduced tendency to recognize novel objects and reduced retention in an inhibitory avoidance task. Water maze testing showed that learning and memory were impaired in irradiated rats for both cue discrimination and spatially oriented tasks. These results demonstrate significant deficits in cortex- and hippocampus-dependent cognitive functions associated with the diffuse abnormalities of cortical and hippocampal development that have been documented in this model. This study documents multimodal cognitive deficits associated with CD and can serve as the foundation for future investigations into the mechanisms of and possible therapeutic interventions for this problem. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  1. Analysis of the 5-HT1A receptor involvement in passive avoidance in the rat

    PubMed Central

    Misane, Ilga; Johansson, Christina; Ove Ögren, Sven

    1998-01-01

    The effects of the 5-HT2A/2C agonist DOB, the selective 5-HT1A agonist NDO 008 (3-dipropylamino-5-hydroxychroman), and the two enantiomers of the selective 5-HT1A agonist 8-OH-DPAT (R(+)-8-OH-DPAT and S(−)-8-OH-DPAT) were studied in a step-through passive avoidance (PA) test in the male rat.The 5-HT1A agonists injected prior to training (conditioning) produced a dose-dependent impairment of PA retention when examined 24 h later. R(+)-8-OH-DPAT was four times more effective than S(−)-8-OH-DPAT to cause an impairment of PA retention. Both NDO 008 and the two enantiomers of 8-OH-DPAT induced the serotonin syndrome at the dose range that produced inhibition of the PA response, thus, indicating activation of postsynaptic 5-HT1A receptors.Neither NDO 008 nor R(+)-8-OH-DPAT induced head-twitches, a behavioural response attributed to stimulation of postsynaptic 5-HT2A receptors. In contrast, DOB induced head-twitches at the 0.01 mg kg−1 dose while a 200 times higher dose was required to produce a significant impairment of PA retention.The impairment of PA retention induced by both NDO 008 and R(+)-8-OH-DPAT was fully blocked by the active S(+)- enantiomer of the selective 5-HT1A antagonist WAY 100135 and the mixed 5-HT1A/β-adrenoceptor antagonist L(−)-alprenolol. In contrast, the mixed 5-HT2A/2C antagonists ketanserin and pirenperone were found to be ineffective. Moreover, the β2-adrenoceptor antagonist ICI 118551, the β1-antagonist metoprolol as well as the mixed β-adrenoceptor blocker D(+)-alprenolol all failed to modify the deficit of PA retention by NDO 008 and R(+)-8-OH-DPAT. None of the 5-HT1A or 5-HT2A/2C receptor antagonists tested or the β-blockers altered PA retention by themselves.A 3 day pretreatment procedure (200+100+100 mg kg−1) with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) did not alter PA retention and did not prevent the inhibitory action of the 5-HT1A agonists, indicating that their effects on PA do not depend on endogenous 5-HT.The effects of NDO 008 on PA were also studied using a state-dependent learning paradigm. NDO 008 was found to produce a disruption of PA when given either prior to training or retention or both prior to training and retention but it failed to affect PA retention when given immediately after training.These findings indicate that the deficit of passive avoidance retention induced by the 5-HT1A agonists is mainly a result of stimulation of postsynaptic 5-HT1A receptors but not 5-HT2A receptors. The 5-HT1A receptor stimulation appears to interfere with learning processes operating at both acquisition and retrieval. PMID:9806333

  2. Effects of aniracetam on one-trial passive avoidance tests and cholinergic neurons in discrete brain regions of rats.

    PubMed

    Toide, K

    1989-01-01

    Using rats in one-trial passive avoidance tests, the anti-amnesic effects of the nootropic drug aniracetam were investigated; moreover, the action of aniracetam upon the cholinergic system in the brain was studied. In one-trial passive avoidance tests, aniracetam prolonged significantly the retention time for 100 mg/kg, p.o. However, the retention-prolonging effect was diminished when the dose was increased to 300 mg/kg p.o. Investigation of the action of the drug upon the cholinergic system revealed that ACh and choline content in the corpus striatum was not increased by any doses of aniracetam. ACh content in the hippocampus was increased by doses of 100-300 mg/kg, p.o., but choline was not significantly increased by any doses, while in the cerebral cortex ACh content was significantly increased by a dose of 300 mg/kg, p.o. In addition, the decrease in hippocampal ACh and choline content following an injection of scopolamine was lessened by aniracetam 100 mg/kg, p.o. and 100-300 mg/kg, respectively. In order to elucidate the mechanism of these actions of aniracetam, the ACh-releasing action and changes in choline content of the extracellular spaces in the hippocampus were investigated, but no effects were observed. The results obtained indicate that aniracetam has an inhibitory effect upon scopolamine-induced amnesia. The mechanism of this effect may be an action upon the cholinergic system; therefore, some action with respect to the impairment of cholinergic neurotransmission in the hippocampus induced by scopolamine appears to be of particular importance.

  3. GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats.

    PubMed

    Rubin, M A; Jurach, A; da Costa Júnior, E M; Lima, T T; Jiménez-Bernal, R E; Begnini, J; Souza, D O; de Mello, C F

    1996-09-02

    Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.

  4. A benzothiazole/piperazine derivative with acetylcholinesterase inhibitory activity: Improvement in streptozotocin-induced cognitive deficits in rats.

    PubMed

    Demir Özkay, Ümide; Can, Özgür Devrim; Sağlık, Begüm Nurpelin; Turan, Nazlı

    2017-12-01

    Acetylcholinesterase (AChE) inhibitors are frequently prescribed to mitigate the cognitive decline in Alzheimer's disease. Thus, we investigated the possible efficacy of the AChE inhibitor 2-[(6-Nitro-2-benzothiazolyl)amino]-2-oxoethyl4-[2-(N,N-dimethylamino)ethyl] piperazine-1 carbodithioate (BPCT) in a streptozotocin (STZ)-induced Alzheimer's disease model (SADM). First, we analyzed the molecular interaction of BPCT with AChE via a docking study. Then, the cognitive effects of BPCT (10 and 20mg/kg) were evaluated in intracerebroventricular STZ- and vehicle-administered rats with the elevated plus maze (EPM), Morris water maze (MWM), and active avoidance (AA) tests. Locomotor activity was also assessed. Docking analysis indicated significant binding of BPCT to the AChE active site. In behavioral tests, STZ administration impaired cognitive performance in SADM rats versus control rats. Treatment with donepezil or BPCT significantly decreased the prolonged 2nd retention transfer latency and 2nd retention latency time values of the SADM group in the EPM and MWM tests, respectively. Further, prolonged latency times were decreased and reduced frequency of avoidance events were increased in the AA test. Locomotor activity between groups was not different. BPCT appears to function as a central AChE inhibitor, and its improvement of deficits in SADM rats suggests that it has therapeutic potential in Alzheimer's disease. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Amygdala kindling-resistant (SLOW) or -prone (FAST) rat strains show differential fear responses.

    PubMed

    Mohapel, P; McIntyre, D C

    1998-12-01

    The authors compared two rat strains, selectively bred for their susceptibility to amygdala kindling, with respect to their performance on various behavioral and learning tasks that are associated with fear and anxiety. The two rat strains differed significantly in measurements of exploration of novel and familiar environments, as well as in reactivity to footshock and fear-based learning. The kindling-resistant (SLOW) strain exhibited a lower ratio of open- to closed-arm entries in the elevated plus-maze, less activity over days in the open field, greater behavioral suppression in the open-field if previously footshocked, greater freezing in the inhibitory avoidance task, and slower acquisition and poorer retention in the one-way avoidance task than did the kindling-prone (FAST) strain. These experiments suggest that the SLOW rats are more expressively fearful than the FAST rats, particularly with respect to environmentally triggered freezing or immobility. Further, these observations imply that the relatively constrained excitability of the amygdala network in the SLOW rats might mediate their relatively greater expression of fear and anxiety compared with the FAST rats.

  6. Amnesia of Inhibitory Avoidance by Scopolamine Is Overcome by Previous Openfield Exposure

    ERIC Educational Resources Information Center

    Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge A.; Jerusalinsky, Diana A.

    2014-01-01

    The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two…

  7. Bombesin administration impairs memory and does not reverse memory deficit caused by sleep deprivation.

    PubMed

    Ferreira, L B T; Oliveira, S L B; Raya, J; Esumi, L A; Hipolide, D C

    2017-07-28

    Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0μg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effects of the antidepressant drug moclobemide on learning and memory in rats.

    PubMed

    Getova, D; Dimitrova, D; Roukounakis, I

    2003-12-01

    Moclobemide is a well known drug with antidepressant action. The aim of this study was to investigate the effects of moclobemide on learning and memory processes in Sprague Dawley rats. Over a 5-day period, learning sessions with 30 trials per day and memory retention tests were performed. The conditioned responses (avoidances), the unconditioned responses (escapes) and the intertrial crossings were observed. An active avoidance test was carried out using a shuttle box. Two passive avoidance tests were used: step-through (using a light chamber) and step-down (using a platform). In the step-through passive avoidance test, the learning and retention sessions consisted of three trials each and the latency of reaction times (the rat remaining in the light chamber for more than 180 sec) was used as criterion. In the step-down passive avoidance test, learning and retention sessions consisted of two trials and the latency of reaction times (the rat remaining on the platform for 60 sec) was used as criterion. In the active avoidance tests, moclobemide dose-dependently increased the number of avoidances during learning sessions and maintained this number in memory retention tests. Moclobemide did not alter the number of escapes, but did increase motor activity. In the passive avoidance tests, moclobemide also increased the latency of reaction times in learning and short memory retrieval tests. These findings suggest that moclobemide improves learning and memory processes in active and passive avoidance tests and has a cognition-enhancing effect. (c) 2003 Prous Science

  9. Drought-avoiding plants with low water use can achieve high rainfall retention without jeopardising survival on green roofs.

    PubMed

    Szota, Christopher; Farrell, Claire; Williams, Nicholas S G; Arndt, Stefan K; Fletcher, Tim D

    2017-12-15

    Green roofs are increasingly being used among the suite of tools designed to reduce the volume of surface water runoff generated by cities. Plants provide the primary mechanism for restoring the rainfall retention capacity of green roofs, but selecting plants with high water use is likely to increase drought stress. Using empirically-derived plant physiological parameters, we used a water balance model to assess the trade-off between rainfall retention and plant drought stress under a 30-year climate scenario. We compared high and low water users with either drought avoidance or drought tolerance strategies. Green roofs with low water-using, drought-avoiding species achieved high rainfall retention (66-81%) without experiencing significant drought stress. Roofs planted with other strategies showed high retention (72-90%), but they also experienced >50days of drought stress per year. However, not all species with the same strategy behaved similarly, therefore selecting plants based on water use and drought strategy alone does not guarantee survival in shallow substrates where drought stress can develop quickly. Despite this, it is more likely that green roofs will achieve high rainfall retention with minimal supplementary irrigation if planted with low water users with drought avoidance strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze.

    PubMed

    Gomes, Karina Santos; de Carvalho-Netto, Eduardo Ferreira; Monte, Kátia Cristina Da Silva; Acco, Bruno; Nogueira, Paulo José de Campos; Nunes-de-Souza, Ricardo Luiz

    2009-03-30

    The elevated T-maze (ETM) is an animal model of anxiety-like behavior that assesses two different defensive behavioral tasks in the same animal-acquisition of inhibitory avoidance and latency to escape from an open and elevated arm. In rats, cute and chronic treatments with anxiolytic-like drugs impair avoidance acquisition while only chronic administration of panicolytic-like drugs impairs open arm withdrawal. To date, only the acute effects of anxiolytic/anxiogenic or panicolytic/panicogenic drugs have been tested in the mouse ETM and the results have partially corroborated those found in the rat ETM. This study investigated the effects of acute (a single intraperitoneal injection 30 min before testing) and chronic (daily i.p. injections for 15 consecutive days) treatment with imipramine or fluoxetine, non-selective and selective serotonin reuptake inhibitors, respectively, on inhibitory avoidance and escape tasks in the mouse ETM. Neither acute nor chronic treatment with imipramine (0, 1, 5 or 10 mg/kg, i.p.) significantly changed the behavioral profile of mice in the two ETM tasks. Interestingly, while acute fluoxetine (0, 5, 10, 20 or 40 mg/kg, i.p.) facilitated inhibitory avoidance and impaired escape latency, chronic treatment (0, 5, 20 or 40 mg/kg, i.p.) with this selective serotonin reuptake inhibitor (SSRI) produced an opposite effect, i.e., it impaired inhibitory avoidance acquisition and facilitated open arm withdrawal. Importantly, acute or chronic treatment with imipramine (except at the highest dose that increased locomotion when given acutely) or fluoxetine failed to alter general locomotor activity in mice as assessed in an ETM in which all arms were enclosed by lateral walls (eETM). These results suggest that inhibitory avoidance acquisition is a useful task for the evaluation of acute and chronic effects of SSRI treatment on anxiety in mice. However, as open arm latency was actually increased and reduced by acute and chronic fluoxetine, respectively, this does not seem to be a useful measure of escape from a proximal threat in this species.

  11. Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties.

    PubMed

    Menze, Esther T; Esmat, Ahmed; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

    2015-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities.

  12. Computational Model of a Positive BDNF Feedback Loop in Hippocampal Neurons Following Inhibitory Avoidance Training

    ERIC Educational Resources Information Center

    Zhang, Yili; Smolen, Paul; Alberini, Cristina M.; Baxter, Douglas A.; Byrne, John H.

    2016-01-01

    Inhibitory avoidance (IA) training in rodents initiates a molecular cascade within hippocampal neurons. This cascade contributes to the transition of short- to long-term memory (i.e., consolidation). Here, a differential equation-based model was developed to describe a positive feedback loop within this molecular cascade. The feedback loop begins…

  13. The Role of Muscarinic and Nicotinic Cholinergic Neurotransmission in Aversive Conditioning: Comparing Pavlovian Fear Conditioning and Inhibitory Avoidance

    ERIC Educational Resources Information Center

    Tinsley, Matthew R.; Quinn, Jennifer J.; Fanselow, Michael S.

    2004-01-01

    Aversive conditioning is an ideal model for studying cholinergic effects on the processes of learning and memory for several reasons. First, deficits produced by selective lesions of the anatomical structures shown to be critical for Pavlovian fear conditioning and inhibitory avoidance (such as the amygdala and hippocampus) resemble those deficits…

  14. Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats.

    PubMed

    Rashidy-Pour, Ali; Vafaei, Abbas Ali; Taherian, Abbas Ali; Miladi-Gorji, Hossein; Sadeghi, Hassan; Fathollahi, Yaghoub; Bandegi, Ahmad Reza

    2009-10-12

    This study was designed to investigate an interaction between acute restraint stress and corticosterone with verapamil, a blocker of L-type voltage-dependent calcium (VDC) channels on retrieval of long-term memory. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On retention test given 48 h after training, the latency to re-enter dark compartment of the apparatus was recorded. In Experiment 1, verapamil pretreatment (5, 10, or 20 mg/kg) enhanced the impairing effects of acute stress (which was applied for 10 min in a Plexiglass tube 30 min before the retention test) on memory retrieval. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress-induced impairment of memory retrieval is mediated, in part, by increased plasma levels of glucocorticoids. Verapamil did not change this response. In Experiment 2, pretreatment of an intermediate dose of verapamil also enhanced corticosterone-induced impairment of memory retrieval. In Experiments 3 and 4, acute stress or corticosterone did not change motor activity with or without prior treatment of verapamil, suggesting that stress or glucocorticoid-induced impairment of memory retrieval is not due to any gross disturbances in motor performance of animals. These findings indicate that blockade of L-type VDC channels enhances stress or glucocorticoid-induced impairment of memory retrieval, and provide evidence for the existence of an interaction between glucocorticoids and L-type VDC channels on memory retrieval.

  15. Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder.

    PubMed

    Morena, Maria; Berardi, Andrea; Peloso, Andrea; Valeri, Daniela; Palmery, Maura; Trezza, Viviana; Schelling, Gustav; Campolongo, Patrizia

    2017-06-30

    Intensive Care Unit (ICU) or emergency care patients, exposed to traumatic events, are at increased risk for Post-Traumatic Stress Disorder (PTSD) development. Commonly used sedative/anesthetic agents can interfere with the mechanisms of memory formation, exacerbating or attenuating the memory for the traumatic event, and subsequently promote or reduce the risk of PTSD development. Here, we evaluated the effects of ketamine, dexmedetomidine and propofol on fear memory consolidation and subsequent cognitive and emotional alterations related to traumatic stress exposure. Immediately following an inhibitory avoidance training, rats were intraperitoneally injected with ketamine (100-125mg/kg), dexmedetomidine (0.3-0.4mg/kg) or their vehicle and tested for 48h memory retention. Furthermore, the effects of ketamine (125mg/kg), dexmedetomidine (0.4mg/kg), propofol (300mg/kg) or their vehicle on long-term memory and social interaction were evaluated two weeks after drug injection in a rat PTSD model. Ketamine anesthesia increased memory retention without altering the traumatic memory strength in the PTSD model. However, ketamine induced a long-term reduction of social behavior. Conversely, dexmedetomidine markedly impaired memory retention, without affecting long-lasting cognitive or emotional behaviors in the PTSD model. We have previously shown that propofol anesthesia enhanced 48h memory retention. Here, we found that propofol induced an enduring traumatic memory enhancement and anxiogenic effects in the PTSD model. These findings provide new evidence for clinical studies showing that the use of ketamine or propofol anesthesia in emergency care and ICU might be more likely to promote the development of PTSD, while dexmedetomidine might have prophylactic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Post-Training Reversible Disconnection of the Ventral Hippocampal-Basolateral Amygdaloid Circuits Impairs Consolidation of Inhibitory Avoidance Memory in Rats

    ERIC Educational Resources Information Center

    Wang, Gong-Wu; Liu, Jian; Wang, Xiao-Qin

    2017-01-01

    The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH-BLA circuit in IA memory consolidation. Male Wistar rats…

  17. Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.

    PubMed

    Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan

    2014-09-01

    We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Prelimbic cortex extracellular signal-regulated kinase 1/2 activation is required for memory retrieval of long-term inhibitory avoidance.

    PubMed

    Luo, Fei; Zheng, Jian; Sun, Xuan; Deng, Wei-Ke; Li, Bao Ming; Liu, Fang

    2017-04-15

    Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABA A -receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-h inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30min prior to test. The present study provides evidence that retrieval of long-lasting memory for inhibitory avoidance requires mPFC and involves the ERK-CREB signaling cascade. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Reversal of prenatal morphine exposure-induced memory deficit in male but not female rats.

    PubMed

    Nasiraei-Moghadam, Shiva; Sherafat, Mohammad Amin; Safari, Mir-Shahram; Moradi, Fatemeh; Ahmadiani, Abolhassan; Dargahi, Leila

    2013-05-01

    Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M₁₋₁₃, or to the time of delivery, M₁₋₂₁. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M₁₋₁₃ and M₁₋₂₁ groups. Adolescent and adult male offspring were similar to control animals in M₁₋₁₃ group. However M₁₋₂₁ impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M₁₋₁₃ and M₁₋₂₁ adolescent and adult female rats, but only in M₁₋₂₁ adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.

  20. Reducing voluntary, avoidable turnover through selection.

    PubMed

    Barrick, Murray R; Zimmerman, Ryan D

    2005-01-01

    The authors investigated the efficacy of several variables used to predict voluntary, organizationally avoidable turnover even before the employee is hired. Analyses conducted on applicant data collected in 2 separate organizations (N = 445) confirmed that biodata, clear-purpose attitudes and intentions, and disguised-purpose dispositional retention scales predicted voluntary, avoidable turnover (rs ranged from -.16 to -.22, R = .37, adjusted R = .33). Results also revealed that biodata scales and disguised-purpose retention scales added incremental validity, whereas clear-purpose retention scales did not explain significant incremental variance in turnover beyond what was explained by biodata and disguised-purpose scales. Furthermore, disparate impact (subgroup differences on race, sex, and age) was consistently small (average d = 0.12 when the majority group scored higher than the minority group).

  1. The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: The involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex.

    PubMed

    Canto-de-Souza, L; Mattioli, R

    2016-04-01

    Several studies using inhibitory avoidance models have demonstrated the importance of limbic structures, such as the amygdala, dorsal hippocampus and medial prefrontal cortex, in the consolidation of emotional memory. However, we aimed to investigate the role of the amygdala (AMG), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) of mice in the consolidation of step-down inhibitory avoidance and whether this avoidance would be conditioned relative to the intensity of the aversive stimulus. To test this, we bilaterally infused anisomycin (ANI-40μg/μl, a protein synthesis inhibitor) into one of these three brain areas in mice. These mice were then exposed to one of two different intensities (moderate: 0.5mA or intense: 1.5mA) in a step-down inhibitory avoidance task. We found that consolidation of both of the aversive experiences was mPFC dependent, while the AMG and DH were only required for the consolidation of the intense experience. We suggest that in moderately aversive situations, which do not represent a severe physical risk to the individual, the consolidation of aversive experiences does not depend on protein synthesis in the AMG or the DH, but only the mPFC. However, for intense aversive stimuli all three of these limbic structures are essential for the consolidation of the experience. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory with Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

    ERIC Educational Resources Information Center

    Miranda, Maria I.; McGaugh, James L.

    2004-01-01

    There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the…

  3. Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats

    PubMed Central

    Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L.; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L.

    2013-01-01

    The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT-7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. PMID:23792034

  4. Central ghrelin increases anxiety in the Open Field test and impairs retention memory in a passive avoidance task in neonatal chicks.

    PubMed

    Carvajal, Pedro; Carlini, Valeria P; Schiöth, Helgi B; de Barioglio, Susana R; Salvatierra, Nancy A

    2009-05-01

    Ghrelin (Grh) is an endogenous ligand for the growth hormone secretagogue receptor. Although Ghr stimulates feeding in rats, it inhibits feeding in neonatal chicks. However, little is known about other central behavioral effects of Ghr. Therefore, we investigated the Ghr effects, injected intracerebroventricularly, on anxiety and memory retention of neonatal chicks in an Open Field test and in a one-trial passive avoidance task, respectively. In the Open Field test, the administration of Ghr in a dose-dependent manner increased the latency to ambulate but decreased ambulation activity, indicating an anxiogenic effect. Furthermore, chicks trained on a passive avoidance task and injected with a dose of 30pmol of Ghr immediately after training showed an impairment of memory retention. However, there were no significant effects on the number of pecks during the pretraining, training, retention and discrimination. In addition, different doses of Ghr produced an inhibition in food intake at different times after injection. Our results indicate that Ghr induces anxiogenesis in chicks. Moreover, we have shown for the first time that Ghr can decrease memory retention in a non-mammalian species, suggesting that Ghr may play an important role in the processes of memory retention in birds.

  5. HPLC-based lipophilicity of pyrrolyl-acetic acid ARIs: Relationships with biological activity.

    PubMed

    Chrysanthakopoulos, Marios; Nicolaou, Ioannis; Demopoulos, Vassilis J; Tsantili-Kakoulidou, Anna

    2010-01-01

    Reversed phase HPLC was used to assess the lipophilicity of a series pyrrolyl-acetic acid derivatives with aldose reductase inhibitory activity. The pH conditions were adjusted at 3.0 to investigate the behavior of the neutral species and at pH 7.4, at which the ionized form predominates, using phosphate and MOPS buffer. Retention was monitored in absence and in presence of different amounts of n-octanol in the mobile phase in order to explore the chromatographic conditions which best reproduce the octanol-water partition or distribution coefficients. The effect of n-octanol in retention was systematically studied and its role in lipophilicity assessment was evaluated. Nevertheless rather moderate regression equations were obtained, which deviated significantly from the ideal 1:1 correlation. No significant effect of buffer was observed. The appropriateness of retention factors to be used in correlation with aldose reductase inhibitory activity was further evaluated and compared to the efficiency of the corresponding octanol-water logP values.

  6. Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body.

    PubMed

    Perisse, Emmanuel; Owald, David; Barnstedt, Oliver; Talbot, Clifford B; Huetteroth, Wolf; Waddell, Scott

    2016-06-01

    In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Interactive contributions of self-regulation deficits and social motivation to psychopathology: Unraveling divergent pathways to aggressive behavior and depressive symptoms

    PubMed Central

    RUDOLPH, KAREN D.; TROOP-GORDON, WENDY; LLEWELLYN, NICOLE

    2015-01-01

    Poor self-regulation has been implicated as a significant risk factor for the development of multiple forms of psychopathology. This research examined the proposition that self-regulation deficits differentially predict aggressive behavior and depressive symptoms, depending on children’s social approach versus avoidance motivation. A prospective, multiple-informant approach was used to test this hypothesis in 419 children (M age = 8.92, SD = 0.36). Parents rated children’s inhibitory control. Children completed measures of social approach–avoidance motivation and depressive symptoms. Teachers rated children’s aggressive behavior. As anticipated, poor inhibitory control predicted aggressive behavior in boys with high but not low approach motivation and low but not high avoidance motivation, whereas poor inhibitory control predicted depressive symptoms in girls with high but not low avoidance motivation. This research supports several complementary theoretical models of psychopathology and provides insight into the differential contributions of poor self-regulation to maladaptive developmental outcomes. The findings suggest the need for targeted intervention programs that consider heterogeneity among children with self-regulatory deficits. PMID:23627953

  8. The integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal inhibitory avoidance memory.

    PubMed

    Giovannini, Maria Grazia; Lana, Daniele; Pepeu, Giancarlo

    2015-03-01

    The purpose of this review is to summarize the present knowledge on the interplay among the cholinergic system, Extracellular signal-Regulated Kinase (ERK) and Mammalian Target of Rapamycin (mTOR) pathways in the development of short and long term memories during the acquisition and recall of the step-down inhibitory avoidance in the hippocampus. The step-down inhibitory avoidance is a form of associative learning that is acquired in a relatively simple one-trial test through several sensorial inputs. Inhibitory avoidance depends on the integrated activity of hippocampal CA1 and other brain areas. Recall can be performed at different times after acquisition, thus allowing for the study of both short and long term memory. Among the many neurotransmitter systems involved, the cholinergic neurons that originate in the basal forebrain and project to the hippocampus are of crucial importance in inhibitory avoidance processes. Acetylcholine released from cholinergic fibers during acquisition and/or recall of behavioural tasks activates muscarinic and nicotinic acetylcholine receptors and brings about a long-lasting potentiation of the postsynaptic membrane followed by downstream activation of intracellular pathway (ERK, among others) that create conditions favourable for neuronal plasticity. ERK appears to be salient not only in long term memory, but also in the molecular mechanisms underlying short term memory formation in the hippocampus. Since ERK can function as a biochemical coincidence detector in response to extracellular signals in neurons, the activation of ERK-dependent downstream effectors is determined, in part, by the duration of ERK phosphorylation itself. Long term memories require protein synthesis, that in the synapto-dendritic compartment represents a direct mechanism that can produce rapid changes in protein content in response to synaptic activity. mTOR in the brain regulates protein translation in response to neuronal activity, thereby modulating synaptic plasticity and long term memory formation. Some studies demonstrate a complex interplay among the cholinergic system, ERK and mTOR. It has been shown that co-activation of muscarinic acetylcholine receptors and β-adrenergic receptors facilitates the conversion of short term to long term synaptic plasticity through an ERK- and mTOR-dependent mechanism which requires translation initiation. It seems therefore that the complex interplay among the cholinergic system, ERK and mTOR is crucial in the development of new inhibitory avoidance memories in the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory.

    PubMed

    Atucha, Erika; Vukojevic, Vanja; Fornari, Raquel V; Ronzoni, Giacomo; Demougin, Philippe; Peter, Fabian; Atsak, Piray; Coolen, Marcel W; Papassotiropoulos, Andreas; McGaugh, James L; de Quervain, Dominique J-F; Roozendaal, Benno

    2017-08-22

    Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock-context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkm ζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.

  10. Retrieval of Inhibitory Avoidance Memory Induces Differential Transcription of arc in Striatum, Hippocampus, and Amygdala.

    PubMed

    González-Salinas, Sofía; Medina, Andrea C; Alvarado-Ortiz, Eduardo; Antaramian, Anaid; Quirarte, Gina L; Prado-Alcalá, Roberto A

    2018-07-01

    Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. We found that arc expression in the striatum increased 30 min after retrieval while no changes were observed in zif268 in this region. Expression of arc and zif268 also increased in the dorsal hippocampus but the changes were attributed to context re-exposure. Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Intra-Amygdala ZIP Injections Impair the Memory of Learned Active Avoidance Responses and Attenuate Conditioned Taste-Aversion Acquisition in Rats

    ERIC Educational Resources Information Center

    Gamiz, Fernando; Gallo, Milagros

    2011-01-01

    We have investigated the effect of protein kinase Mzeta (PKM[zeta]) inhibition in the basolateral amygdala (BLA) upon the retention of a nonspatial learned active avoidance response and conditioned taste-aversion (CTA) acquisition in rats. ZIP (10 nmol/[mu]L) injected into the BLA 24 h after training impaired retention of a learned…

  12. Differences in Active Avoidance Conditioning in Male and Female Rats with Experimental Anxiety-Depressive Disorder.

    PubMed

    Khlebnikova, N N; Krupina, N A; Kushnareva, E Yu; Orlova, I N

    2015-07-01

    Using rat model of experimental anxiety-depressive disorder caused by postnatal administration of methionyl-2(S)-cyanopyrrolidine, an inhibitor of dipeptidyl peptidase IV, we compared conditioned active avoidance response and memory retention in males and females. In experimental males and females, conditioning was impaired in comparison with the control. In experimental groups, females were worse learners than males, while in control groups, females were better learners than males. Memory retention in experimental animals did not differ from that in controls 24 h after learning. Two months after learning, control females demonstrated better retention than control males.

  13. GABA[subscript A] Receptors Determine the Temporal Dynamics of Memory Retention

    ERIC Educational Resources Information Center

    McNally, Gavan P.; Augustyn, Katarzyna A.; Richardson, Rick

    2008-01-01

    Four experiments studied the role of GABA[subscript A] receptors in the temporal dynamics of memory retention. Memory for an active avoidance response was a nonmonotonic function of the retention interval. When rats were tested shortly (2 min) or some time (24 h) after training, retention was excellent, but when they were tested at intermediate…

  14. Modification of CO2 avoidance behaviour in Drosophila by inhibitory odorants.

    PubMed

    Turner, Stephanie Lynn; Ray, Anandasankar

    2009-09-10

    The fruitfly Drosophila melanogaster exhibits a robust and innate olfactory-based avoidance behaviour to CO(2), a component of odour emitted from stressed flies. Specialized neurons in the antenna and a dedicated neuronal circuit in the higher olfactory system mediate CO(2) detection and avoidance. However, fruitflies need to overcome this avoidance response in some environments that contain CO(2) such as ripening fruits and fermenting yeast, which are essential food sources. Very little is known about the molecular and neuronal basis of this unique, context-dependent modification of innate olfactory avoidance behaviour. Here we identify a new class of odorants present in food that directly inhibit CO(2)-sensitive neurons in the antenna. Using an in vivo expression system we establish that the odorants act on the Gr21a/Gr63a CO(2) receptor. The presence of these odorants significantly and specifically reduces CO(2)-mediated avoidance behaviour, as well as avoidance mediated by 'Drosophila stress odour'. We propose a model in which behavioural avoidance to CO(2) is directly influenced by inhibitory interactions of the novel odours with CO(2) receptors. Furthermore, we observe differences in the temporal dynamics of inhibition: the effect of one of these odorants lasts several minutes beyond the initial exposure. Notably, animals that have been briefly pre-exposed to this odorant do not respond to the CO(2) avoidance cue even after the odorant is no longer present. We also show that related odorants are effective inhibitors of the CO(2) response in Culex mosquitoes that transmit West Nile fever and filariasis. Our findings have broader implications in highlighting the important role of inhibitory odorants in olfactory coding, and in their potential to disrupt CO(2)-mediated host-seeking behaviour in disease-carrying insects like mosquitoes.

  15. Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task.

    PubMed

    Nasehi, Mohammad; Morteza-Zadeh, Parastoo; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

    2016-12-17

    In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABA A receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABA A receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABA A receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABA A receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats.

    PubMed

    Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L

    2013-10-01

    The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT--7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory

    PubMed Central

    Atucha, Erika; Vukojevic, Vanja; Fornari, Raquel V.; Ronzoni, Giacomo; Demougin, Philippe; Peter, Fabian; Atsak, Piray; Coolen, Marcel W.; Papassotiropoulos, Andreas; McGaugh, James L.; de Quervain, Dominique J.-F.; Roozendaal, Benno

    2017-01-01

    Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock–context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory. PMID:28790188

  18. Nootropic activity of extracts from wild and cultivated Alfredia cernua.

    PubMed

    Mustafin, R N; Shilova, I V; Suslov, N I; Kuvacheva, N V; Amelchenko, V P

    2011-01-01

    Antihypoxic and nootropic activities of extracts from aerial parts of wild and cultivated Alfredia cernua (L.) Cass. were studied on the models of pressure chamber hypoxia, open field test, and passive avoidance conditioning. The extracts of Alfredia cernua promoted retention of the orientation reflex and passive avoidance conditioned response and normalized orientation and exploratory activities disordered as a result of hypoxic injury. The efficiency of the extracts was superior to that of piracetam by the effect on retention of passive avoidance response throughout the greater part of the experiment. Nootropic activity of cultivated Alfredia cernua was not inferior to that of the wild plant.

  19. [Influence of activation and blockade of NMDA receptors on extinction of passive avoidance response in mice with different levels of anxiety].

    PubMed

    Tomilenko, R A; Dubrovina, N I

    2006-03-01

    Influence of agonist (D-cycloserine) and antagonist (dizocilpine) N-methyl-D-aspartate receptors on learning and extinction of passive avoidance response in medium-, high-, and low-anxious mice was studied. In medium-anxious mice, D-cycloserine (30 mg/kg) although not changing learning accelerated development of extinction, whereas dizocilpine (0.15 mg/kg), while impairing passive avoidance learning, detained the extinction. In high-anxious mice with good retrieval of memory trace and absence of extinction, D-cycloserine was ineffective, whereas dizocilpine reduced learning and promoted retention of memory trace retrieval at the generated level on extinction. In low-anxious mice, D-cycloserine impaired learning and accelerated extinction, whereas dizocilpine completely blocked learning and retention of passive avoidance response.

  20. Beneficial effect of commercial Rhodiola extract in rats with scopolamine-induced memory impairment on active avoidance.

    PubMed

    Vasileva, Liliya V; Getova, Damianka P; Doncheva, Nina D; Marchev, Andrey S; Georgiev, Milen I

    2016-12-04

    Rhodiola rosea L., family Crassulaceae also known as Golden Root or Arctic root is one of the most widely used medicinal plants with effect on cognitive dysfunction, psychological stress and depression. The aim of the study was to examine the effect of a standardized commercial Rhodiola extract on learning and memory processes in naive rats as well as its effects in rats with scopolamine-induced memory impairment. Sixty male Wistar rats were used in the study. The experiment was conducted in two series - on naive rats and on rats with scopolamine-induced model of impaired memory. The active avoidance test was performed in an automatic conventional shuttle box set-up. The criteria used were the number of conditional stimuli (avoidances), the number of unconditioned stimuli (escapes) as well as the number of intertrial crossings. The chemical fingerprinting of the standardized commercial Rhodiola extract was performed by means of nuclear magnetic resonance (NMR). Naive rats treated with standardized Rhodiola extract increased the number of avoidances during the learning session and memory retention test compared to the controls. Rats with scopolamine-induced memory impairment treated with Rhodiola extract showed an increase in the number of avoidances during the learning session and on the memory tests compared to the scopolamine group. The other two parameters were not changed in rats treated with the extract of Rhodiola in the two series. It was found that the studied Rhodiola extract exerts a beneficial effect on learning and memory processes in naive rats and rats with scopolamine-induced memory impairment. The observed effect is probably due to multiple underlying mechanisms including its modulating effect on acetylcholine levels in the brain and MAO-inhibitory activity leading to stimulation of the monoamines' neurotransmission. In addition the pronounced stress-protective properties of Rhodiola rosea L. could also play a role in the improvement of cognitive functions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. An economic assessment of local farm multi-purpose surface water retention systems in a Canadian Prairie setting

    NASA Astrophysics Data System (ADS)

    Berry, Pamela; Yassin, Fuad; Belcher, Kenneth; Lindenschmidt, Karl-Erich

    2017-12-01

    There is a need to explore more sustainable approaches to water management on the Canadian Prairies. Retention pond installation schemes designed to capture surface water may be a viable option that would reduce water stress during drought periods by providing water for irrigation. The retention systems would serve to capture excess spring runoff and extreme rainfall events, reducing flood potential downstream. Additionally, retention ponds may be used for biomass production and nutrient retention. The purpose of this research was to investigate the economic viability of adopting local farm surface water retention systems as a strategic water management strategy. A retention pond was analyzed using a dynamic simulation model to predict its storage capacity, installation and upkeep cost, and economic advantage to farmers when used for irrigation. While irrigation application increased crop revenue, the cost of irrigation and reservoir infrastructure and installation costs were too high for the farmer to experience a positive net revenue. Farmers who harvest cattails from retention systems for biomass and available carbon offset credits can gain 642.70/hectare of harvestable cattail/year. Cattail harvest also removes phosphorus and nitrogen, providing a monetized impact of 7014/hectare of harvestable cattail/year. The removal of phosphorus, nitrogen, carbon, and avoided flooding damages of the retention basin itself provide an additional 17,730-18,470/hectare of retention system/year. The recommended use of retention systems is for avoided flood damages, nutrient retention, and biomass production. The revenue gained from these functions can support farmers wanting to invest in irrigation while providing economic and environmental benefits to the region.

  2. Potential effects of reward and loss avoidance in overweight adolescents.

    PubMed

    Reyes, Sussanne; Peirano, Patricio; Luna, Beatriz; Lozoff, Betsy; Algarín, Cecilia

    2015-08-01

    Reward system and inhibitory control are brain functions that exert an influence on eating behavior regulation. We studied the differences in inhibitory control and sensitivity to reward and loss avoidance between overweight/obese and normal-weight adolescents. We assessed 51 overweight/obese and 52 normal-weight 15-y-old Chilean adolescents. The groups were similar regarding sex and intelligence quotient. Using Antisaccade and Incentive tasks, we evaluated inhibitory control and the effect of incentive trials (neutral, loss avoidance, and reward) on generating correct and incorrect responses (latency and error rate). Compared to normal-weight group participants, overweight/obese adolescents showed shorter latency for incorrect antisaccade responses (186.0 (95% CI: 176.8-195.2) vs. 201.3 ms (95% CI: 191.2-211.5), P < 0.05) and better performance reflected by lower error rate in incentive trials (43.6 (95% CI: 37.8-49.4) vs. 53.4% (95% CI: 46.8-60.0), P < 0.05). Overweight/obese adolescents were more accurate on loss avoidance (40.9 (95% CI: 33.5-47.7) vs. 49.8% (95% CI: 43.0-55.1), P < 0.05) and reward (41.0 (95% CI: 34.5-47.5) vs. 49.8% (95% CI: 43.0-55.1), P < 0.05) compared to neutral trials. Overweight/obese adolescents showed shorter latency for incorrect responses and greater accuracy in reward and loss avoidance trials. These findings could suggest that an imbalance of inhibition and reward systems influence their eating behavior.

  3. Time course of scopolamine effect on memory consolidation and forgetting in rats.

    PubMed

    Popović, Miroljub; Giménez de Béjar, Verónica; Popović, Natalija; Caballero-Bleda, María

    2015-02-01

    The effect of scopolamine on the consolidation and forgetting of emotional memory has not been completely elucidated yet. The aim of the present study was to investigate the time course of scopolamine effect on consolidation and forgetting of passive avoidance response. In a first experiment of the present study, we tested the effect of scopolamine (1mg/kg, i.p., immediately after acquisition), on 24h and 48h retention performance of the step-through passive avoidance task, in adult male Wistar rats. On the 24h retested trial, the latency of the passive avoidance response was significantly lower, while on the 48h retested trial it was significantly higher in scopolamine than in the saline-treated group. In a second experiment, we assessed the 24h time course of scopolamine (1mg/kg) effect on memory consolidation in passive avoidance task. We found that scopolamine administration only within the first six and half hours after acquisition improved memory consolidation in 48h retention performance. Finally, a third experiment was performed on the saline- and scopolamine-treated rats (given immediately after acquisition) that on the 48h retention test did not step through into the dark compartment during the cut-off time. These animals were retested weekly for up to first three months, and after that, every three months until the end of experiment (i.e., 15 months after acquisition). The passive avoidance response in the saline treated group lasted up to 6 weeks after acquisition, while in the scopolamine treated group 50% of animals conserved the initial level of passive avoidance response until the experiment end point. In conclusion, the present data suggest that (1) improving or impairment effect of scopolamine given in post-training periods depends on delay of retention trial, (2) memory consolidation process could be modify by scopolamine within first six and half hours after training and (3) scopolamine could delay forgetting of emotional memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice.

    PubMed

    Tabrizian, Kaveh; Yazdani, Abdolmajid; Baheri, Behnam; Payandemehr, Borna; Sanati, Mehdi; Hashemzaei, Mahmoud; Miri, Abdolhossein; Zandkarimi, Majid; Belaran, Maryam; Fanoudi, Sahar; Sharifzadeh, Mohammad

    2016-01-01

    It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

  5. Effects of ethanolic extract and naphthoquinones obtained from the bulbs of Cipura paludosa on short-term and long-term memory: involvement of adenosine A₁ and A₂A receptors.

    PubMed

    Lucena, Greice M R S; Matheus, Filipe C; Ferreira, Vania M; Tessele, Priscila B; Azevedo, Mariangela S; Cechinel-Filho, Valdir; Prediger, Rui D

    2013-04-01

    Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

  6. TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition.

    PubMed

    Blank, Martina; Petry, Fernanda S; Lichtenfels, Martina; Valiati, Fernanda E; Dornelles, Arethuza S; Roesler, Rafael

    2016-03-01

    Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.

  7. Behavioral consequences of predator stress in the rat elevated T-maze.

    PubMed

    Bulos, Erika Mondin; Pobbe, Roger Luis Henschel; Zangrossi, Helio

    2015-07-01

    Analyses of the behavioral reactions of rodents to predators have greatly contributed to the understanding of defense-related human psychopathologies such as anxiety and panic.We here investigated the behavioral consequences of exposing male Wistar rats to a live cat using the elevated T-maze test of anxiety. This test allows the measurement of two defensive responses: inhibitory avoidance and escape, which in terms of pathology have been associated with generalized anxiety and panic disorders, respectively. For comparative reasons, the effects of exposure to the cat were also assessed in the elevated plus-maze. The results showed that a 5-min exposure to the cat selectively facilitated inhibitory avoidance acquisition, an anxiogenic effect, without affecting escape expression in the elevated T-maze. This was seen immediately but not 30 min after contact with the predator. This short-lived anxiogenic effect was also detected in the elevated plus-maze. Previous administration of the benzodiazepine anxiolytic diazepam (2 mg/kg) decreased the immediate avoidance response to the predator and the neophobic reaction to a dummy cat used as a control stimulus. The drug also impaired inhibitory avoidance acquisition in the elevated T-maze, indicating an anxiolytic effect, without affecting escape performance. The results indicate that the state of anxiety evoked during contact with the predator generalizes to both elevated plus- and T-mazes, impacting on defensive responses associated with generalized anxiety disorder.

  8. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats.

    PubMed

    Ghosh, Arijit; Dhumal, V R; Tilak, A V; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A

    2011-01-01

    To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

  9. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

    PubMed Central

    Ghosh, Arijit; Dhumal, V. R.; Tilak, A. V.; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A.

    2011-01-01

    Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions. PMID:21701638

  10. Novel Technologies for Next Generation Memory

    DTIC Science & Technology

    2013-07-25

    charge in the capacitor) eventually fades unless the capacitor charge is refreshed , so the memory cells must be periodically refreshed (rewritten). The...reliability issues (such as poor data retention problem and refresh failure). In order to avoid those problems, a 3-dimensional channel structure...states during the refresh cycle (retention time). When the channel length is scaled down, it is difficult to guarantee sufficient retention time

  11. Potential effects of reward and loss avoidance in overweight adolescents

    PubMed Central

    Reyes, Sussanne; Peirano, Patricio; Luna, Beatriz; Lozoff, Betsy; Algarín, Cecilia

    2015-01-01

    Background Reward system and inhibitory control are brain functions that exert an influence on eating behavior regulation. We studied the differences in inhibitory control and sensitivity to reward and loss avoidance between overweight/obese and normal-weight adolescents. Methods We assessed 51 overweight/obese and 52 normal-weight 15-y-old Chilean adolescents. The groups were similar regarding sex and intelligence quotient. Using Antisaccade and Incentive tasks, we evaluated inhibitory control and the effect of incentive trials (neutral, loss avoidance, and reward) on generating correct and incorrect responses (latency and error rate). Results Compared to normal-weight group participants, overweight/obese adolescents showed shorter latency for incorrect antisaccade responses (186.0 (95% CI: 176.8–195.2) vs. 201.3 ms (95% CI: 191.2–211.5), P < 0.05) and better performance reflected by lower error rate in incentive trials (43.6 (95% CI: 37.8–49.4) vs. 53.4% (95% CI: 46.8–60.0), P < 0.05). Overweight/obese adolescents were more accurate on loss avoidance (40.9 (95% CI: 33.5–47.7) vs. 49.8% (95% CI: 43.0–55.1), P < 0.05) and reward (41.0 (95% CI: 34.5–47.5) vs. 49.8% (95% CI: 43.0–55.1), P < 0.05) compared to neutral trials. Conclusion Overweight/obese adolescents showed shorter latency for incorrect responses and greater accuracy in reward and loss avoidance trials. These findings could suggest that an imbalance of inhibition and reward systems influence their eating behavior. PMID:25927543

  12. Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

    PubMed

    Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

    2002-12-01

    Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

  13. "To be or not to be Retained … That's the Question!" Retention, Self-esteem, Self-concept, Achievement Goals, and Grades.

    PubMed

    Peixoto, Francisco; Monteiro, Vera; Mata, Lourdes; Sanches, Cristina; Pipa, Joana; Almeida, Leandro S

    2016-01-01

    Keeping students back in the same grade - retention - has always been a controversial issue in Education, with some defending it as a beneficial remedial practice and others arguing against its detrimental effects. This paper undertakes an analysis of this issue, focusing on the differences in student motivation and self-related variables according to their retention related status, and the interrelationship between retention and these variables. The participants were 695 students selected from two cohorts (5th and 7th graders) of a larger group of students followed over a 3-year project. The students were assigned to four groups according to their retention-related status over time: (1) students with past and recent retention; (2) students with past but no recent retention; (3) students with no past but recent retention; (4) students with no past or recent retention. Measures of achievement goal orientations, self-concept, self-esteem, importance given to school subjects and Grade Point Average (GPA) were collected for all students. Repeated measures MANCOVA analyses were carried out showing group differences in self-esteem, academic self-concept, importance attributed to academic competencies, task and avoidance orientation and academic achievement. To attain a deeper understanding of these results and to identify profiles across variables, a cluster analysis based on achievement goals was conducted and four clusters were identified. Students who were retained at the end of the school year are mainly represented in clusters with less adaptive motivational profiles and almost absent from clusters exhibiting more adaptive ones. Findings highlight that retention leaves a significant mark that remains even when students recover academic achievement and retention is in the distant past. This is reflected in the low academic self-concept as well as in the devaluation of academic competencies and in the avoidance orientation which, taken together, can undermine students' academic adjustment and turn retention into a risk factor.

  14. “To be or not to be Retained … That’s the Question!” Retention, Self-esteem, Self-concept, Achievement Goals, and Grades

    PubMed Central

    Peixoto, Francisco; Monteiro, Vera; Mata, Lourdes; Sanches, Cristina; Pipa, Joana; Almeida, Leandro S.

    2016-01-01

    Keeping students back in the same grade – retention – has always been a controversial issue in Education, with some defending it as a beneficial remedial practice and others arguing against its detrimental effects. This paper undertakes an analysis of this issue, focusing on the differences in student motivation and self-related variables according to their retention related status, and the interrelationship between retention and these variables. The participants were 695 students selected from two cohorts (5th and 7th graders) of a larger group of students followed over a 3-year project. The students were assigned to four groups according to their retention-related status over time: (1) students with past and recent retention; (2) students with past but no recent retention; (3) students with no past but recent retention; (4) students with no past or recent retention. Measures of achievement goal orientations, self-concept, self-esteem, importance given to school subjects and Grade Point Average (GPA) were collected for all students. Repeated measures MANCOVA analyses were carried out showing group differences in self-esteem, academic self-concept, importance attributed to academic competencies, task and avoidance orientation and academic achievement. To attain a deeper understanding of these results and to identify profiles across variables, a cluster analysis based on achievement goals was conducted and four clusters were identified. Students who were retained at the end of the school year are mainly represented in clusters with less adaptive motivational profiles and almost absent from clusters exhibiting more adaptive ones. Findings highlight that retention leaves a significant mark that remains even when students recover academic achievement and retention is in the distant past. This is reflected in the low academic self-concept as well as in the devaluation of academic competencies and in the avoidance orientation which, taken together, can undermine students’ academic adjustment and turn retention into a risk factor. PMID:27790167

  15. TRIMETHYLTIN IMPAIRS RETENTION OF A PASSIVE AVOIDANCE TASK

    EPA Science Inventory

    Trimethyltin is a neurotoxic organometal which produces neuronal damage in several limbic regions including the hippocampus, amygdala and the pyriform cortex. One administration of trimethyltin (5,6 or 7 mg/kg) twenty one days prior to passive avoidance conditioning produced an i...

  16. Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents.

    PubMed

    Cumin, R; Bandle, E F; Gamzu, E; Haefely, W E

    1982-01-01

    The effect of aniracetam (Ro 13-5057, 1-anisoyl-2-pyrrolidinone) was studied on various forms of experimentally impaired cognitive functions (learning and memory) in rodents and produced the following effects: (1) almost complete prevention of the incapacity to learn a discrete escape response in rats exposed to sublethal hypercapnia immediately before the acquisition session; (2) partial (rats) or complete (mice) prevention of the scopolamine-induced short-term amnesia for a passive avoidance task; (3) complete protection against amnesia for a passive avoidance task in rats submitted to electroconvulsive shock immediately after avoidance acquisition; (4) prevention of the long-term retention- or retrieval-deficit for a passive avoidance task induced in rats and mice by chloramphenicol or cycloheximide administered immediately after acquisition; (5) reversal, when administered as late as 1 h before the retention test, of the deficit in retention or retrieval of a passive avoidance task induced by cycloheximide injected 2 days previously; (6) prevention of the deficit in the retrieval of an active avoidance task induced in mice by subconvulsant electroshock or hypercapnia applied immediately before retrieval testing (24 h after acquisition). These improvements or normalizations of impaired cognitive functions were seen at oral aniracetam doses of 10-100 mg/kg. Generally, the dose-response curves were bell-shaped. The mechanisms underlying the activity of aniracetam and its 'therapeutic window' are unknown. Piracetam, another pyrrolidinone derivative was used for comparison. It was active only in six of nine tests and had about one-tenth the potency of aniracetam. The results indicate that aniracetam improves cognitive functions which are impaired by different procedure and in different phases of the learning and memory process.

  17. Semi-continuous anaerobic co-digestion of cow manure and steam-exploded Salix with recirculation of liquid digestate.

    PubMed

    Estevez, Maria M; Sapci, Zehra; Linjordet, Roar; Schnürer, Anna; Morken, John

    2014-04-01

    The effects of recirculating the liquid fraction of the digestate during mesophilic anaerobic co-digestion of steam-exploded Salix and cow manure were investigated in laboratory-scale continuously stirred tank reactors. An average organic loading rate of 2.6 g VS L(-1) d(-1) and a hydraulic retention time (HRT) of 30 days were employed. Co-digestion of Salix and manure gave better methane yields than digestion of manure alone. Also, a 16% increase in the methane yield was achieved when digestate was recirculated and used instead of water to dilute the feedstock (1:1 dilution ratio). The reactor in which the larger fraction of digestate was recirculated (1:3 dilution ratio) gave the highest methane yields. Ammonia and volatile fatty acids did not reach inhibitory levels, and some potentially inhibitory compounds released during steam explosion (i.e., furfural and 5-hydroxy methyl furfural) were only detected at trace levels throughout the entire study period. However, accumulation of solids, which was more pronounced in the recycling reactors, led to decreased methane yields in those systems after three HRTs. Refraining from the use of fresh water to dilute biomass with a high-solids content and obtaining a final digestate with increased dry matter content might offer important economic benefits in full-scale processes. To ensure long-term stability in such an approach, it would be necessary to optimize separation of the fraction of digestate to be recirculated and also perform proper monitoring to avoid accumulation of solids. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

    PubMed

    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-06-22

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve-ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats, these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost, but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. By contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared with sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  19. Participation of muscarinic receptors in memory consolidation in passive avoidance learning.

    PubMed

    Dobryakova, Yulia V; Gurskaya, Olga; Markevich, Vladimir A

    2014-01-01

    It is well-known that the cholinergic system and the muscarinic cholinergic receptors are associated with cognitive functions. Here we examined whether a non-selective muscarinic receptor antagonist scopolamine affects learning performance and/or synaptic plasticity during the memory consolidation period. Adult male Wistar rats (250-300 g) were injected with scopolamine (2 mg/kg) or saline immediately after training in a "passive avoidance" task. Memory retention test was conducted 24 h after training. The changes in the latency of the first entry into a dark compartment of a test chamber was chosen as a criterion of learning. The efficacy of synaptic transmission was estimated by the changes in the basal level of focal potentials (fEPSP amplitude and slope ratio) before training (baseline), 90 min after the training (consolidation period), and 24 hour after the training (retention period). We found that foot-shock presentation by itself had no effect on fEPSP within the first 90 min after training, but in 24 hour fEPSPs were decreased. In untrained rats administration of scopolamine had no effect on the fEPSP amplitude within the first 90 min after the injection, but in 24 h we observed an increase in the fEPSP amplitude. In trained animals, scopolamine decreased the fEPSP amplitude in the hippocampal CA1 area during first 1.5 h after the injection. However, the drug had no effect on the memory retention in the passive avoidance task. Taken together our data suggest that scopolamine modifies the synaptic placticity of the hippocampal network but does not induce significant changes in the retention of the passive avoidance skill.

  20. Allergens retained in clothing.

    PubMed

    Nedorost, Susan; Kessler, Margaret; McCormick, Thomas

    2007-12-01

    Some patients state compliance with avoidance of identified allergens, yet have persistent dermatitis in areas under tight-fitting clothing. To analyze a series of such cases to identify allergens most likely retained in clothing. Review of contact dermatitis clinic cases and identification of type and formula weight of allergens involved. High-formula-weight allergens and allergens present in medicament ointments are difficult to dissolve in laundry detergent and water and may be retained in clothing. Retention of allergens in clothing, even after washing, may explain recalcitrant dermatitis in a patient who states compliance with avoidance of a seemingly relevant allergen. Dermatologists should consider the possibility of allergen retention in clothing whenever a patient has only partial clearing after at least 1 month of attempted compliance with avoidance of identified allergens. Purchase of new clothing may be required to clear allergic contact dermatitis in this situation.

  1. C(5)-C(5a)-modified bicyclomycins: synthesis, structure, and biochemical and biological properties.

    PubMed

    Vincent, F; Srinivasan, J; Santillán, A; Widger, W R; Kohn, H

    2001-04-06

    Bicyclomycin (1) is a novel antibiotic that targets rho transcription termination factor in Escherichia coli. We have demonstrated that retention of the C(5)-C(5a) exomethylene unit in 1 is not essential for inhibition. In a recent paper we proposed a working model for 1 and rho function and suggested that 1 binds in a cleft with the C(5)-C(5a) exomethylene unit directed toward the dimeric interface of two rho monomers. This report examines the bicyclomycin C(5)-C(5a) structural constraints necessary for retention of rho inhibitory activity. Three classes of C(5)-C(5a)-modified bicyclomycins have been prepared and their inhibitory activities evaluated in the poly C-dependent ATPase and filter disk antimicrobial assays. The first series consisted of 12 analogues (8-19) that contained a C(5a)-unsaturated substituent and possessed C(5E)-geometry. The second set were a pair of C(5a)-substituted C(5E)- and C(5Z)-geometrical isomers (21 and 23). The final group of compounds consisted of six C(5)-C(5a)-dihydrobicyclomycins (24-28, 34) where the terminal substituent was systematically varied. We find that extending the C(5)-C(5a) double bond with unsaturated substituents provides bicyclomycin derivatives with excellent inhibitory activities in the biochemical assay, and that enhanced inhibitory activity is observed for the C(5E) geometrical isomer compared with its C(5Z) counterpart. Finally, C(5a)-substituted dihydrobicyclomycin inhibitory activity appears to be tightly regulated by the nature and spatial placement of the C(5a)-terminal substituent with respect to the [4.2.2]-bicyclic ring system. The observed biochemical activities for the C(5a)-extended conjugated bicyclomycin derivatives and the (5E) and (5Z) isomers were correlated with a structural model for the 1-rho complex.

  2. Avoiding the Potential Pitfalls of Using Negative Priming Tasks in Developmental Studies: Assessing Inhibitory Control in Children, Adolescents, and Adults

    ERIC Educational Resources Information Center

    Pritchard, Verena E.; Neumann, Ewald

    2009-01-01

    Despite being ignored, visual distractors often produce traceable negative priming (NP) effects that can be used to investigate inhibitory processes. Robust NP effects are typically found with young adults, but not with children. Using 2 different NP tasks, the authors compared NP in 5 different age groups spanning 5 to 25 years of age. The 1st…

  3. Effects of activation and blockade of NMDA receptors on the extinction of a conditioned passive avoidance response in mice with different levels of anxiety.

    PubMed

    Tomilenko, R A; Dubrovina, N I

    2007-06-01

    The effects of an agonist (D-cycloserine) and an antagonist (dizocilpine) of N-methyl-D-aspartate (NMDA) receptors on the learning and extinction of a conditioned passive avoidance response were studied in mice with low, intermediate, and high levels of anxiety. In intermediate-anxiety mice, D-cycloserine (30 mg/kg) had no effect on learning but accelerated extinction, while dizocilpine (0.15 mg/kg) degraded acquisition of the reflex but delayed extinction. In high-anxiety mice, with good learning and no extinction, D-cycloserine had no effect, while dizocilpine decreased learning and facilitated retention of performance of the memory trace at the ongoing level in conditions promoting extinction. In low-anxiety mice, D-cycloserine degraded learning and accelerated extinction, while dizocilpine completely blocked learning and the retention of the passive avoidance response.

  4. Semantic Integration as a Boundary Condition on Inhibitory Processes in Episodic Retrieval

    ERIC Educational Resources Information Center

    Goodmon, Leilani B.; Anderson, Michael C.

    2011-01-01

    Recalling an experience often impairs the later retention of related traces, a phenomenon known as retrieval-induced forgetting (RIF). Research has shown that episodic associations protect competing memories from RIF (Anderson & McCulloch, 1999). We report 4 experiments that examined whether semantic associations also protect against RIF. In…

  5. Threat Interference Biases Predict Socially Anxious Behavior: The Role of Inhibitory Control and Minute of Stressor.

    PubMed

    Gorlin, Eugenia I; Teachman, Bethany A

    2015-07-01

    The current study brings together two typically distinct lines of research. First, social anxiety is inconsistently associated with behavioral deficits in social performance, and the factors accounting for these deficits remain poorly understood. Second, research on selective processing of threat cues, termed cognitive biases, suggests these biases typically predict negative outcomes, but may sometimes be adaptive, depending on the context. Integrating these research areas, the current study examined whether conscious and/or unconscious threat interference biases (indexed by the unmasked and masked emotional Stroop) can explain unique variance, beyond self-reported anxiety measures, in behavioral avoidance and observer-rated anxious behavior during a public speaking task. Minute of speech and general inhibitory control (indexed by the color-word Stroop) were examined as within-subject and between-subject moderators, respectively. Highly socially anxious participants (N=135) completed the emotional and color-word Stroop blocks prior to completing a 4-minute videotaped speech task, which was later coded for anxious behaviors (e.g., speech dysfluency). Mixed-effects regression analyses revealed that general inhibitory control moderated the relationship between both conscious and unconscious threat interference bias and anxious behavior (though not avoidance), such that lower threat interference predicted higher levels of anxious behavior, but only among those with relatively weaker (versus stronger) inhibitory control. Minute of speech further moderated this relationship for unconscious (but not conscious) social-threat interference, such that lower social-threat interference predicted a steeper increase in anxious behaviors over the course of the speech (but only among those with weaker inhibitory control). Thus, both trait and state differences in inhibitory control resources may influence the behavioral impact of threat biases in social anxiety. Copyright © 2015. Published by Elsevier Ltd.

  6. Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

    PubMed

    Azambuja, Amanda Stapenhorst; Correa, Lilian; Gabiatti, Bernardo Pappi; Martins, Giselle Renata; de Oliveira Franco, Álvaro; Ribeiro, Maria Flávia Marques; Baldo, Guilherme

    2018-02-01

    Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

  7. [Herpes zoster infection with acute urinary retention].

    PubMed

    Jakab, G; Komoly, S; Juhász, E

    1990-03-11

    The history of a young female patient is presented. She developed urine retention of sudden onset as a complication of herpes zoster infection manifested in the sacral dermatomes. Symptomatic and antiviral treatments were introduced with full recovery of bladder function. The correct diagnosis of this rare and benign complication of herpes zoster infection can help to avoid unnecessary and invasive examinations.

  8. Effects of histamine and some related compounds on conditioned avoidance response in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tasaka, K.; Kamei, C.; Akahori, H.

    1985-11-25

    When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 ..mu..g. l-methylHi, l-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 ..mu..g. H/sub 1/-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H/sub 2/-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydraminemore » and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5-hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H/sub 1/-receptor. After intraventricular application of /sup 3/H-Hi, the highest radioactivity was determined in the hypothalamus. 21 references, 4 figures, 4 tables.« less

  9. Avoiding a Pilot Retention Death Spiral: The Pilot Shortage and DOD’s Challenge to Maintain an Effective Fighting Force

    DTIC Science & Technology

    2018-04-09

    pilot retention, they must move beyond solely seeing retention as a money issue and instead address the entire pilot system from production to pay...Shortage is All About the Money ,” ALPA.org, February 27, 2014, http://www.alpa.org/news-and-events/news-room/2014-02-27-Pilot-Shortage-All-About... Money (accessed October 17, 2017). 15 Air Line Pilots Association, “The Landing,” Air Line Pilot Vol. 84, No. 6 (August 2015): 37, http://www3.alpa.org

  10. Effects of alismol isolated from Alismatis Rhizoma on calcium-induced contraction in the rabbit thoracic aorta

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsuda, H.; Kobayashi, G.; Yamahara, J.

    1987-10-12

    The authors examined the inhibitory effects of alismol, a sesquiterpenoid isolated from Alismatis Rhizoma, on vascular contractions induced by high concentrations of K/sup +/ and Ca/sup 2 +/, and on /sup 45/Ca/sup 2 +/ retention in normal and in high K/sup +/-containing medium. Alismol affected neither the resting tension nor the /sup 45/Ca/sup 2 +/ retention in normal medium, but it inhibited sustained contraction and increased /sup 45/Ca/sup 2 +/ retention induced by high K/sup +/ concentrations. Alismol did not affect norepinephrine-induced contractions in normal medium, nor phasic contractions in Ca/sup 2 +/-free medium. These results suggested that alismol inhibitedmore » mainly Ca/sup 2 +/ influx through a voltage-dependent Ca/sup 2 +/ channel. 19 references, 6 figures.« less

  11. Gap junctions and memory: an investigation using a single trial discrimination avoidance task for the neonate chick.

    PubMed

    Verwey, L J; Edwards, T M

    2010-02-01

    Gap junctions are important to how the brain functions but are relatively under-investigated with respect to their contribution towards behaviour. In the present study a single trial discrimination avoidance task was used to investigate the effect of the gap junction inhibitor 18-alpha-glycyrrhetinic acid (alphaGA) on retention. Past studies within our research group have implied a potential role for gap junctions during the short-term memory (STM) stage which decays by 15 min post-training. A retention function study comparing 10 microM alphaGA and vehicle given immediately post-training demonstrated a significant main effect for drug with retention loss at all times of test (10-180 min post-training). Given that the most common gap junction in the brain is that forming the astrocytic network it is reasonable to conclude that alphaGA was acting upon these. To confirm this finding and interpretation two additional investigations were undertaken using endothelin-1 (ET-1) and ET-1+tolbutamide. Importantly, a retention function study using 10nM ET-1 replicated the retention loss observed for alphaGA. In order to confirm that ET-1 was acting on astrocytic gap junctions the amnestic action of ET-1 was effectively challenged with increasing concentrations of tolbutamide. The present findings suggest that astrocytic gap junctions are important for memory processing. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

    PubMed Central

    Menezes, Jefferson; Alves, Niége; Borges, Sidnei; Roehrs, Rafael; de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Izquierdo, Ivan; Mello-Carpes, Pâmela B.

    2015-01-01

    Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors. PMID:25775606

  13. Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment.

    PubMed

    Zhang, Kun; Li, Pei; He, Yaping; Bo, Xiaowan; Li, Xiaolong; Li, Dandan; Chen, Hangrong; Xu, Huixiong

    2016-08-01

    Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Relationship between changes in rat behavior and integral biochemical indexes determined by laser correlation spectroscopy after photothrombosis of the prefrontal cortex.

    PubMed

    Romanova, G A; Shakova, F M; Kovaleva, O I; Pivovarov, V V; Khlebnikova, N N; Karganov, M Yu

    2004-02-01

    Experiments on rats showed that Noopept improved retention and retrieval of conditioned passive avoidance response after phototrombosis of the prefrontal cortex (a procedure impairing retention of memory traces). The impairment of mnesic functions was accompanied by changes in integral biochemical indexes of the plasma determined by laser correlation spectroscopy. Treatment of behavioral disorders with Noopepet normalized biochemical indexes.

  15. Trypsin inhibitory activity and gel-enhancing effect of sarcoplasmic proteins from common carp.

    PubMed

    Siriangkanakun, Siriphon; Yongsawatdigul, Jirawat

    2012-10-01

    Proteinase inhibitory activity of sarcoplasmic protein (SP) extracted from common carp (Cyprinus carpio) muscle and its gel-improving ability were investigated. SPs displayed 89% and 54% inhibitory activity toward trypsin at 40 and 65 °C, respectively. Protein bands with molecular mass of 69, 50, 44, 41, and 35 kDa appeared on trypsin inhibitory activity staining under nonreducing condition when incubated at 40 °C, while 2 protein bands at 54 and 35 kDa were observed at 65 °C. Addition of SP at 0.18 g protein/100 g increased textural properties of threadfin bream surimi gel. However, when SP was added in combination with various CaCl(2) concentrations (0.1% to 0.5%) it did not further improve textural properties as compared to the addition of SP alone. Retention of myosin heavy chain of threadfin bream surimi was greater with the addition of SP. These results indicated that the gel-enhancing effect of common carp SP was due to the inhibitory activity toward endogenous trypsin-like proteinases in threadfin bream surimi. Sarcoplasmic protein from common carp muscle could be used as a functional protein ingredient that minimizes muscle proteolysis and improves textural properties of surimi containing trypsin-like endogenous proteinases. © 2012 Institute of Food Technologists®

  16. Motivation, working memory, and decision making: a cognitive-motivational theory of personality vulnerability to alcoholism.

    PubMed

    Finn, Peter R

    2002-09-01

    This article presents a cognitive-motivational theory (CMT) of the mechanisms associated with three basic dimensions of personality vulnerability to alcoholism, impulsivity/novelty seeking, harm avoidance, and excitement seeking. CMT describes the interrelationships between activity in basic motivational systems and attentional, decision-making and working memory processes as the mechanisms associated with variation in each personality trait. Impulsivity/novelty seeking reflects activity in both appetitive and inhibitory motivational systems, greater attention to reward cues, and increased emotional reactivity to reward and frustration. Harm avoidance reflects individual differences in fearfulness and activity in specific inhibitory systems. Excitement seeking reflects the need to engage in appetitive behaviors in less predictable environments to experience positive affect. CMT also describes the impact of working memory and the specific motivational processes underlying each trait dimension on the dynamics of decision making from the perspective of decision field theory.

  17. Role of renal sensory nerves in physiological and pathophysiological conditions

    PubMed Central

    2014-01-01

    Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

  18. Acute urinary retention due to benign inflammatory nervous diseases.

    PubMed

    Sakakibara, Ryuji; Yamanishi, Tomonori; Uchiyama, Tomoyuki; Hattori, Takamichi

    2006-08-01

    Both neurologists and urologists might encounter patients with acute urinary retention due to benign inflammatory nervous diseases. Based on the mechanism of urinary retention, these disorders can be divided into two subgroups: disorders of the peripheral nervous system (e.g., sacral herpes) or the central nervous system (e.g., meningitis-retention syndrome [MRS]). Laboratory abnormalities include increased herpes virus titers in sacral herpes, and increased myelin basic protein in the cerebrospinal fluid (CSF) in some cases with MRS. Urodynamic abnormality in both conditions is detrusor areflexia; the putative mechanism of it is direct involvement of the pelvic nerves in sacral herpes; and acute spinal shock in MRS. There are few cases with CSF abnormality alone. Although these cases have a benign course, management of the acute urinary retention is necessary to avoid bladder injury due to overdistension. Clinical features of sacral herpes or MRS differ markedly from those of the original "Elsberg syndrome" cases.

  19. mTORC1 controls long-term memory retrieval.

    PubMed

    Pereyra, Magdalena; Katche, Cynthia; de Landeta, Ana Belén; Medina, Jorge H

    2018-06-08

    Understanding how stored information emerges is a main question in the neurobiology of memory that is now increasingly gaining attention. However, molecular events underlying this memory stage, including involvement of protein synthesis, are not well defined. Mammalian target of rapamycin complex 1 (mTORC1), a central regulator of protein synthesis, has been implicated in synaptic plasticity and is required for memory formation. Using inhibitory avoidance (IA), we evaluated the role of mTORC1 in memory retrieval. Infusion of a selective mTORC1 inhibitor, rapamycin, into the dorsal hippocampus 15 or 40 min but not 3 h before testing at 24 h reversibly disrupted memory expression even in animals that had already expressed IA memory. Emetine, a general protein synthesis inhibitor, provoked a similar impairment. mTORC1 inhibition did not interfere with short-term memory retrieval. When infused before test at 7 or 14 but not at 28 days after training, rapamycin impaired memory expression. mTORC1 blockade in retrosplenial cortex, another structure required for IA memory, also impaired memory retention. In addition, pretest intrahippocampal rapamycin infusion impaired object location memory retrieval. Our results support the idea that ongoing protein synthesis mediated by activation of mTORC1 pathway is necessary for long but not for short term memory.

  20. Effect of Free Ammonia, Free Nitrous Acid, and Alkalinity on the Partial Nitrification of Pretreated Pig Slurry, Using an Alternating Oxic/Anoxic SBR

    PubMed Central

    Hsieh, Chia-Fang; Guerrero, Lorna; Méndez, Ramón; Mosquera-Corral, Anuska; Vidal, Gladys

    2017-01-01

    The effect of free ammonia (NH3 or FA), free nitrous acid (HNO2 or FNA), and total alkalinity (TA) on the performance of a partial nitrification (PN) sequencing batch reactor (SBR) treating anaerobically pretreated pig slurry was studied. The SBR was operated under alternating oxic/anoxic (O/A) conditions and was fed during anoxic phases. This strategy allowed using organic matter to partially remove nitrite (NO2−) and nitrate (NO3−) generated during oxic phases. The desired NH4+ to NO2− ratio of 1.3 g N/g N was obtained when an Ammonium Loading Rate (ALR) of 0.09 g NH4+-N/L·d was applied. The system was operated at a solid retention time (SRT) of 15–20 d and dissolved oxygen (DO) levels higher than 3 mg O2/L during the whole operational period. PN mainly occurred caused by the inhibitory effect of FNA on nitrite oxidizing bacteria (NOB). Once HNO2 concentration was negligible, NH4+ was fully oxidized to NO3− in spite of the presence of FA. The use of biomass acclimated to ammonium as inoculum avoided a possible effect of FA on NOB activity. PMID:29018815

  1. Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction.

    PubMed

    Petry, Fernanda S; Dornelles, Arethuza S; Lichtenfels, Martina; Valiati, Fernanda E; de Farias, Caroline Brunetto; Schwartsmann, Gilberto; Parent, Marise B; Roesler, Rafael

    2016-07-01

    Hippocampal gastrin-releasing peptide receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Mucous retention cyst of temporal bone: a mimic of cholesteatoma on DW-MRI.

    PubMed

    Karandikar, Amit; Goh, Julian; Loke, Siu Cheng; Yeo, Seng Beng; Tan, Tiong Yong

    2013-01-01

    Non-EPI DW imaging is increasingly being used as a sensitive sequence in detecting cholesteatomas especially if CT findings are not confirmatory. Cholesteatoma appears as a hyperintense focus on DWI. We present two cases of mucous retention cysts in the mastoid temporal bone/middle ear cavity, which present as hyperintense on non-EPI DWI and potentially may mimic cholesteatomas. Differentiating between the two conditions is important, as surgery can be avoided in mucous retention cysts. We have also discussed ways to differentiate between these two conditions on MRI. To our knowledge, this entity is not reported previously. © 2013 Elsevier Inc. All rights reserved.

  3. The effects of aging on the working memory processes of multimodal information.

    PubMed

    Solesio-Jofre, Elena; López-Frutos, José María; Cashdollar, Nathan; Aurtenetxe, Sara; de Ramón, Ignacio; Maestú, Fernando

    2017-05-01

    Normal aging is associated with deficits in working memory processes. However, the majority of research has focused on storage or inhibitory processes using unimodal paradigms, without addressing their relationships using different sensory modalities. Hence, we pursued two objectives. First, was to examine the effects of aging on storage and inhibitory processes. Second, was to evaluate aging effects on multisensory integration of visual and auditory stimuli. To this end, young and older participants performed a multimodal task for visual and auditory pairs of stimuli with increasing memory load at encoding and interference during retention. Our results showed an age-related increased vulnerability to interrupting and distracting interference reflecting inhibitory deficits related to the off-line reactivation and on-line suppression of relevant and irrelevant information, respectively. Storage capacity was impaired with increasing task demands in both age groups. Additionally, older adults showed a deficit in multisensory integration, with poorer performance for new visual compared to new auditory information.

  4. Neural mechanisms of motivated forgetting

    PubMed Central

    Anderson, Michael C.; Hanslmayr, Simon

    2014-01-01

    Not all memories are equally welcome in awareness. People limit the time they spend thinking about unpleasant experiences, a process that begins during encoding, but that continues when cues later remind someone of the memory. Here, we review the emerging behavioural and neuroimaging evidence that suppressing awareness of an unwelcome memory, at encoding or retrieval, is achieved by inhibitory control processes mediated by the lateral prefrontal cortex. These mechanisms interact with neural structures that represent experiences in memory, disrupting traces that support retention. Thus, mechanisms engaged to regulate momentary awareness introduce lasting biases in which experiences remain accessible. We argue that theories of forgetting that neglect the motivated control of awareness omit a powerful force shaping the retention of our past. PMID:24747000

  5. Cue avoidance training and inhibitory control training for the reduction of alcohol consumption: a comparison of effectiveness and investigation of their mechanisms of action.

    PubMed

    Di Lemma, Lisa C G; Field, Matt

    2017-08-01

    Both cue avoidance training (CAT) and inhibitory control training (ICT) reduce alcohol consumption in the laboratory. However, these interventions have never been directly compared and their mechanisms of action are poorly understood. We compared the effects of both types of training on alcohol consumption and investigated if they led to theoretically predicted changes in alcohol avoidance (CAT) or alcohol inhibition (ICT) associations and changes in evaluation of alcohol cues. Heavy drinking young adults (N = 120) were randomly assigned to one of four groups: (1) CAT (repeatedly pushing alcohol cues away with a joystick), (2) sham (control) CAT; (3) ICT (repeatedly inhibiting behaviour in response to alcohol cues); or (4) sham (control) ICT. Changes in reaction times and automatic evaluations of alcohol cues were assessed before and after training using assessment versions of tasks used in training and the implicit association test (IAT), respectively. Finally, participants completed a bogus taste test as a measure of ad libitum alcohol consumption. Compared to sham conditions, CAT and ICT both led to reduced alcohol consumption although there was no difference between the two. Neither intervention affected performance on the IAT, and changes in reaction time did not suggest the formation of robust alcohol avoidance (CAT) or alcohol inhibition (ICT) associations after training. CAT and ICT yielded equivalent reductions in alcohol consumption in the laboratory. However, these behavioural effects were not accompanied by devaluation of stimuli or the formation of alcohol avoidance or alcohol inhibition associations.

  6. Improving retention of older employees through training and development.

    PubMed

    Tourigny, Louise; Pulich, Marcia

    2006-01-01

    This article explores the needs and interests of older employees in training and development efforts which can result in higher retention rates. Managers may be reluctant to train workers close to retirement age for various reasons. Managers also use certain practices to avoid training older employees. When training is offered, accurate performance feedback is essential for desired training outcomes to occur. Finally, areas are proposed which are more appropriate to include in training and development endeavors for older employees versus younger ones.

  7. Editorial Commentary: Graft Removal Versus Retention for Septic Arthritis After Anterior Cruciate Ligament Reconstruction: Accounting for Patient Preference Flips the Script on Current Practice.

    PubMed

    Cote, Mark P

    2018-03-01

    Septic arthritis is a rare but potentially devastating complication after anterior cruciate ligament (ACL) reconstruction. Studies examining surgical treatment options including graft retention and removal are largely inconclusive. Although the literature indicated that 43.8% of patients who have the graft removed later go on to have a revision ACL reconstruction compared with only 6.5% among those whose graft is retained, this expected-value decision analysis found removal to be the optimal treatment for patients with septic arthritis after ACL reconstruction. This is largely based on patient preference to avoid a late reoperation for residual knee infection. These findings support the concept of utility when considering treatment options for patients with a septic knee. For some, avoiding a late reoperation for a persistent infection is the most important factor and as such graft removal may be the most appropriate treatment to produce a positive outcome among these patients despite the fact that currently, an attempt at graft retention could represent the generally preferred treatment option among practicing surgeons. Copyright © 2017. Published by Elsevier Inc.

  8. Stimulation of postsynapse adrenergic α2A receptor improves attention/cognition performance in an animal model of attention deficit hyperactivity disorder.

    PubMed

    Kawaura, Kazuaki; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

    2014-08-15

    A 5-trial inhibitory avoidance test using spontaneously hypertensive rat (SHR) pups has been used as an animal model of attention deficit hyperactivity disorder (ADHD). However, the roles of noradrenergic systems, which are involved in the pathophysiology of ADHD, have not been investigated in this model. In the present study, the effects of adrenergic α2 receptor stimulation, which has been an effective treatment for ADHD, on attention/cognition performance were investigated in this model. Moreover, neuronal mechanisms mediated through adrenergic α2 receptors were investigated. We evaluated the effects of both clonidine, a non-selective adrenergic α2 receptor agonist, and guanfacine, a selective adrenergic α2A receptor agonist, using a 5-trial inhibitory avoidance test with SHR pups. Juvenile SHR exhibited a shorter transfer latency, compared with juvenile Wistar Kyoto (WKY) rats. Both clonidine and guanfacine significantly prolonged the transfer latency of juvenile SHR. The effects of clonidine and guanfacine were significantly blocked by pretreatment with an adrenergic α2A receptor antagonist. In contrast, the effect of clonidine was not attenuated by pretreatment with an adrenergic α2B receptor antagonist, or an adrenergic α2C receptor antagonist, while it was attenuated by a non-selective adrenergic α2 receptor antagonist. Furthermore, the effects of neither clonidine nor guanfacine were blocked by pretreatment with a selective noradrenergic neurotoxin. These results suggest that the stimulation of the adrenergic α2A receptor improves the attention/cognition performance of juvenile SHR in the 5-trial inhibitory avoidance test and that postsynaptic, rather than presynaptic, adrenergic α2A receptor is involved in this effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.

    PubMed

    de Noronha, Sylvana Rendeiro; Campos, Glenda Viggiano; Abreu, Aline Rezende; de Souza, Aline Arlindo; Chianca, Deoclécio A; de Menezes, Rodrigo C

    2017-01-01

    Overweight and obesity are conditions associated with an overall range of clinical health consequences, and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH). However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes in obese rats still remains unclear. The current study further investigates the relation between obesity and generalized anxiety, by investigating the GABA A sensitivity to pharmacological manipulation within the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45% w/w). Animals were randomly treated with muscimol, a GABA A agonist and bicuculline methiodide (BMI), a GABA A antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition, suggesting a positive relation between obesity and the development of an anxiety-like state. The injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors, probably through changes in the GABAergic neurotransmission within the DMH. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Memory Formation: Evidence for a Specific Neurochemical System in the Amygdala

    ERIC Educational Resources Information Center

    Gallagher, Michela; And Others

    1977-01-01

    Reports bita-Adrenergic antagonists injected into rats trained in a passive avoidance task produced time-dependent and dose-dependent decreases in retention of the task. Results were stereospecific and reversed by norepinephrine. (SL)

  11. Defective GABAergic neurotransmision and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of Fragile X Syndrome

    PubMed Central

    Olmos-Serrano, Jose Luis; Paluszkiewicz, Scott M.; Martin, Brandon S.; Kaufmann, Walter E.; Corbin, Joshua G.; Huntsman, Molly M.

    2010-01-01

    Fragile X Syndrome (FXS) is a neurodevelopmental disorder characterized by variable cognitive impairment and behavioural disturbances such as exaggerated fear, anxiety and gaze avoidance. Consistent with this, findings from human brain imaging studies suggest dysfunction of the amygdala. Underlying alterations in amygdala synaptic function in the Fmr1 knockout (KO) mouse model of FXS, however, remain largely unexplored. Utilizing a combination of approaches, we uncover profound alterations in inhibitory neurotransmission in the amygdala of Fmr1 KO mice. We demonstrate a dramatic reduction in the frequency and amplitude of phasic inhibitory postsynaptic currents (IPSCs), tonic inhibitory currents, as well as in the number of inhibitory synapses in Fmr1 KO mice. Furthermore, we observe significant alterations in GABA availability, both intracellularly and at the synaptic cleft. Together, these findings identify abnormalities in basal and action potential-dependent inhibitory neurotransmission. Additionally, we reveal a significant neuronal hyperexcitability in principal neurons of the amygdala in Fmr1 KO mice, which is strikingly rescued by pharmacological augmentation of tonic inhibitory tone using the GABA agonist, gaboxadol (THIP). Thus, our study reveals relevant inhibitory synaptic abnormalities in the amygdala in the Fmr1 KO brain and supports the notion that pharmacological approaches targeting the GABAergic system may be a viable therapeutic approach toward correcting amygdala-based symptoms in FXS. PMID:20660275

  12. Enhancing effects of chronic lithium on memory in the rat.

    PubMed

    Tsaltas, Eleftheria; Kontis, Dimitrios; Boulougouris, Vasileios; Papakosta, Vasiliki-Maria; Giannou, Haralambos; Poulopoulou, Cornelia; Soldatos, Constantine

    2007-02-12

    In spite of recent enrichment of neurochemical and behavioural data establishing a neuroprotective role for lithium, its primary effects on cognitive functioning remain ambiguous. This study examines chronic lithium effects on spatial working memory and long-term retention. In three discrete experiments, rats subjected to 30 daily intraperitoneal injections (2mmol/kg) of lithium (lithium groups: serum lithium=0.5+/-0.4mEq/l, 12h post-injection) or saline (controls) were trained in 0-s delay T-maze alternation and then tested in 30-, 45- and 60-s delay alternation (Experiments 1, 2, 3, respectively). Animals from Experiment 1 were further tested in one-trial step-through passive avoidance under mild shock parameters (0.5mA, 1s). Retention was assessed 6h later. Daily lithium or saline injections continued throughout behavioural testing. Lithium animals were indistinguishable from controls during 0-delay alternation baseline (Experiments 1-3, accuracy>88%) but showed significantly higher accuracy than controls at 30- and 45-s delays (93% versus 85% and 92% versus 82%, Experiments 1 and 2, respectively). At 60-s delay (Experiment 3) this beneficial effect of lithium was no longer apparent (lithium and control accuracy=78%). In Experiment 4, the shock used did not support 6-h passive avoidance retention in controls, whereas lithium animals showed significant step-through latency increases. Chronic lithium enhanced spatial working memory and promoted long-term retention of a weak aversive contingency. The results suggest that lithium may have potential as a cognitive enhancer.

  13. Desiccation tolerance of Sphagnum revisited: a puzzle resolved.

    PubMed

    Hájek, T; Vicherová, E

    2014-07-01

    As ecosystem engineers, Sphagnum mosses control their surroundings through water retention, acidification and peat accumulation. Because water retention avoids desiccation, sphagna are generally intolerant to drought; however, the literature on Sphagnum desiccation tolerance (DT) provides puzzling results, indicating the inducible nature of their DT. To test this, various Sphagnum species and other mesic bryophytes were hardened to drought by (i) slow drying; (ii) ABA application and (iii) chilling or frost. DT tolerance was assessed as recovery of chlorophyll fluorescence parameters after severe desiccation. We monitored the seasonal course of DT in bog bryophytes. Under laboratory conditions, following initial de-hardening, untreated Sphagnum shoots lacked DT; however, DT was induced by all hardening treatments except chilling, notably by slow drying, and in Sphagnum species of the section Cuspidata. In the field, sphagna in hollows and lawns developed DT several times during the growing season, responding to reduced precipitation and a lowered water table. Hummock and aquatic species developed DT only in late autumn, probably as a response to frost. Sphagnum protonemata failed to develop DT; hence, desiccation may limit Sphagnum establishment in drier habitats with suitable substrate chemistry. Desiccation avoiders among sphagna form compact hummocks or live submerged; thus, they do not develop DT in the field, lacking the initial desiccation experience, which is frequent in hollow and lawn habitats. We confirmed the morpho-physiological trade-off: in contrast to typical hollow sphagna, hummock species invest more resources in water retention (desiccation avoidance), while they have a lower ability to develop physiological DT. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  14. Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats.

    PubMed

    Mora, S; Dussaubat, N; Díaz-Véliz, G

    1996-10-01

    The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased open-arm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.

  15. Neural circuits via which single prolonged stress exposure leads to fear extinction retention deficits

    PubMed Central

    Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions critical for extinction retention (i.e., fear extinction circuit). These were the ventral hippocampus (vHipp), dorsal hippocampus (dHipp), basolateral amygdala (BLA), prelimbic cortex (PL), and infralimbic cortex (IL). SPS or control rats were fear conditioned then subjected to extinction training and testing. Subsets of rats were euthanized after extinction training, extinction testing, or immediate removal from the housing colony (baseline condition) to assay c-Fos levels (measure of neural activity) in respective brain region. SPS induced extinction retention deficits. During extinction training SPS disrupted enhanced IL neural activity and inhibited BLA neural activity. SPS also disrupted inhibited BLA and vHipp neural activity during extinction testing. Statistical analyses suggested that SPS disrupted functional connectivity within the dHipp during extinction training and increased functional connectivity between the BLA and vHipp during extinction testing. Our findings suggest that SPS induces extinction retention deficits by disrupting both excitatory and inhibitory changes in neural activity within the fear extinction circuit and inducing changes in functional connectivity within the Hipp and BLA. PMID:27918273

  16. Food Avoidance Learning in Squirrel Monkeys and Common Marmosets

    PubMed Central

    Laska, Matthias; Metzker, Karin

    1998-01-01

    Using a conditioned food avoidance learning paradigm, six squirrel monkeys (Saimiri sciureus) and six common marmosets (Callithrix jacchus) were tested for their ability to (1) reliably form associations between visual or olfactory cues of a potential food and its palatability and (2) remember such associations over prolonged periods of time. We found (1) that at the group level both species showed one-trial learning with the visual cues color and shape, whereas only the marmosets were able to do so with the olfactory cue, (2) that all individuals from both species learned to reliably avoid the unpalatable food items within 10 trials, (3) a tendency in both species for quicker acquisition of the association with the visual cues compared with the olfactory cue, (4) a tendency for quicker acquisition and higher reliability of the aversion by the marmosets compared with the squirrel monkeys, and (5) that all individuals from both species were able to reliably remember the significance of the visual cues, color and shape, even after 4 months, whereas only the marmosets showed retention of the significance of the olfactory cues for up to 4 weeks. Furthermore, the results suggest that in both species tested, illness is not a necessary prerequisite for food avoidance learning but that the presumably innate rejection responses toward highly concentrated but nontoxic bitter and sour tastants are sufficient to induce robust learning and retention. PMID:10454364

  17. Synthesis study on transverse variable asphalt application rates for seal coats.

    DOT National Transportation Integrated Search

    2009-06-01

    This report documents a cooperative effort to collect, process, and make available information about successful methods of varying seal coat asphalt application rates across treated roadways to optimize aggregate retention and avoid wheel path flushi...

  18. Addressing employee turnover and retention: keeping your valued performers.

    PubMed

    McConnell, Charles R

    2011-01-01

    Employee turnover and employee retention are inextricably linked; to control turnover is to enhance retention. Turnover is a relatively simple concept; however, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some that can be corrected and some that cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role; every improvement in turnover is a direct improvement in retention, with eventual positive effects on the bottom line.

  19. [Advantages and disadvantages of endocrown restorations of endodontically treated teeth with large coronal destruction].

    PubMed

    Bao, X D

    2018-04-09

    The strength of endodontically treated teeth were reduced apparently because of structural damage, therefore further reduction of healthy tissue should be avoided as much as possible in restoration. Endocrown made by chair-side CAD/CAM is some kind of minimal invasive restoration, and the retention of restoration is achieved by reliable bonding and macromechanial retention forces. Without post preparation, the root structure could be resevered. Following the indications and use of biomechanical dentin-like CAD/CAM materials could reduce the adverse effect of tensile stress on cervical part.

  20. Retrieval Does Not Induce Reconsolidation of Inhibitory Avoidance Memory

    ERIC Educational Resources Information Center

    Medina, Jorge H.; Izquierdo, Ivan; Cammarota, Martin; Bevilaqua, Lia R. M.

    2004-01-01

    It has been suggested that retrieval during a nonreinforced test induces reconsolidation instead of extinction of the mnemonic trace. Reconsolidation would preserve the original memory from the labilization induced by its nonreinforced recall through a hitherto uncharacterized mechanism requiring protein synthesis. Given the importance that such a…

  1. Low arsenic concentrations impair memory in rat offpring exposed during pregnancy and lactation: Role of α7 nicotinic receptor, glutamate and oxidative stress.

    PubMed

    Mónaco, Nina María; Bartos, Mariana; Dominguez, Sergio; Gallegos, Cristina; Bras, Cristina; Esandi, María Del Carmen; Bouzat, Cecilia; Giannuzzi, Leda; Minetti, Alejandra; Gumilar, Fernanda

    2018-04-17

    Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Arsenic exposure has been associated to cognitive deficits. However, the underlying mechanisms remain unknown. In the present work we investigated in female adult offspring the effect of the exposure to low arsenite sodium levels through drinking water during pregnancy and lactation on short- and long-term memory. We also considered a possible underlying neurotoxic mechanism. Pregnant rats were exposed during pregnancy and lactation to environmentally relevant iAs concentrations (0.05 and 0.10 mg/L). In 90-day-old female offspring, short-term memory (STM) and long-term memory (LTM) were evaluated using a step-down inhibitory avoidance task. In addition, we evaluated the α7 nicotinic receptor (α7-nAChR) expression, the transaminases and the oxidative stress levels in hippocampus. The results showed that the exposure to 0.10 mg/L iAs in this critical period produced a significant impairment in the LTM retention. This behavioral alteration might be associated with several events that occur in the hippocampus: decrease in α7-nAChR expression, an increase of glutamate levels that may produce excitotoxicity, and a decrease in the antioxidant enzyme catalase (CAT) activity. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Retention of colonoscopy skills after virtual reality simulator training by independent and proctored methods.

    PubMed

    Snyder, Christopher W; Vandromme, Marianne J; Tyra, Sharon L; Hawn, Mary T

    2010-07-01

    Virtual reality (VR) simulators may enhance surgical resident colonoscopy skills, but the duration of skill retention and the effects of different simulator training methods are unknown. Medical students participating in a randomized trial of independent (automated simulator feedback only) versus proctored (human expert feedback plus simulator feedback) simulator training performed a standardized VR colonoscopy scenario at baseline, at the end of training (posttraining), and after a median 4.5 months without practice (retention). Performances were scored on a 10-point scale based on expert proficiency criteria and compared for the independent and proctored groups. Thirteen trainees (8 proctored, 5 independent) were included. Performance at retention testing was significantly better than baseline (median score 10 vs. 5, P < 0.0001), and no different from posttraining (median score 10 vs. 10, P = 0.19). Score changes from baseline to retention and from posttraining to retention were no different for the proctored and independent groups. Overinsufflation and excessive force were the most common reasons for nonproficiency at retention. After proficiency-based VR simulator training, colonoscopy skills are retained for several months, regardless of whether an independent or proctored approach is used. Error avoidance skills may not be retained as well as speed and efficiency skills.

  3. Retention period after treatment of posterior crossbite with maxillary expansion: a systematic review.

    PubMed

    Costa, Julia Garcia; Galindo, Thaís Magalhães; Mattos, Claudia Trindade; Cury-Saramago, Adriana de Alcantara

    2017-01-01

    The aim of this systematic review was to evaluate the duration of the retention period in growing patients undergoing maxillary expansion and its relation with posterior crossbite stability. Search strategies were executed for electronic databases Cochrane Library, Web of Science, PubMed and Scopus, which were completed on January 15, 2016. The inclusion criteria included randomized, prospective or retrospective controlled trials in growing subjects with posterior crossbite; treated with maxillary expanders; retention phase after expansion; post-retention phase of at least 6 months. The exclusion criteria were anterior crossbite, craniofacial anomalies, surgery or another orthodontic intervention; case reports; author's opinions articles, thesis, literature reviews and systematic reviews. The risk of bias of selected articles was assessed with Cochrane risk of bias tool for RCTs and Downs and Black checklist for non-RCTs. A total of 156 titles/abstracts was retrieved, 44 full-texts were examined, and 6 articles were selected and assessed for their methodological quality. The retention period after maxillary expansion ranged between 4 weeks and 16 months. Fixed (acrylic plate, Haas, Hyrax and quad-helix) or removable (Hawley and Hawley expander) appliances were used for retention. Six months of retention with either fixed or removable appliances seem to be enough to avoid relapse or to guarantee minimal changes in a short-term follow-up.

  4. Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome.

    PubMed

    Olmos-Serrano, Jose Luis; Paluszkiewicz, Scott M; Martin, Brandon S; Kaufmann, Walter E; Corbin, Joshua G; Huntsman, Molly M

    2010-07-21

    Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by variable cognitive impairment and behavioral disturbances such as exaggerated fear, anxiety and gaze avoidance. Consistent with this, findings from human brain imaging studies suggest dysfunction of the amygdala. Underlying alterations in amygdala synaptic function in the Fmr1 knock-out (KO) mouse model of FXS, however, remain largely unexplored. Utilizing a combination of approaches, we uncover profound alterations in inhibitory neurotransmission in the amygdala of Fmr1 KO mice. We demonstrate a dramatic reduction in the frequency and amplitude of phasic IPSCs, tonic inhibitory currents, as well as in the number of inhibitory synapses in Fmr1 KO mice. Furthermore, we observe significant alterations in GABA availability, both intracellularly and at the synaptic cleft. Together, these findings identify abnormalities in basal and action potential-dependent inhibitory neurotransmission. Additionally, we reveal a significant neuronal hyperexcitability in principal neurons of the amygdala in Fmr1 KO mice, which is strikingly rescued by pharmacological augmentation of tonic inhibitory tone using the GABA agonist gaboxadol (THIP). Thus, our study reveals relevant inhibitory synaptic abnormalities in the amygdala in the Fmr1 KO brain and supports the notion that pharmacological approaches targeting the GABAergic system may be a viable therapeutic approach toward correcting amygdala-based symptoms in FXS.

  5. Edible bioactive fatty acid-cellulosic derivative composites used in food-packaging applications.

    PubMed

    Sebti, Issam; Ham-Pichavant, Frédérique; Coma, Véronique

    2002-07-17

    To develop biodegradable packaging that both acts as a moisture barrier and as antimicrobial activity, nisin and stearic acid were incorporated into a hydroxy propyl methyl cellulose (HPMC) based film. Fifteen percent (w/w HPMC) of stearic acid improved film moisture barrier. However, film mechanical resistance and film antimicrobial activity on Listeria monocytogenes and Staphylococcus aureus pathogenic strains were both reduced. This lower film inhibitory activity was due to interactions between nisin and stearic acid. The molecular interaction was modeled, and an equation was developed to calculate the nisin concentration needed to be incorporated into the film matrix to obtain a desired residual antimicrobial activity. Because the molecular interactions were pH dependent, the impact of the pH of the film-forming solution on film inhibitory activity was investigated. Adjusting the pH to 3 totally avoided stearic acid and nisin interaction, inducing a high film inhibitory activity.

  6. Processing demands in belief-desire reasoning: inhibition or general difficulty?

    PubMed

    Friedman, Ori; Leslie, Alan M

    2005-05-01

    Most 4-year-olds can predict the behavior of a person who wants an object but is mistaken about its location. More difficult is predicting behavior when the person is mistaken about location and wants to avoid the object. We tested between two explanations for children's difficulties with avoidance false belief: the Selection Processing model of inhibitory processing and a General Difficulty account. Children were presented with a false belief task and a control task, in which belief attribution was as difficult as in the false belief task. Predicting behavior in light of the character's desire to avoid the object added more difficulty in the false belief task. This finding is consistent with the Selection Processing model, but not with the General Difficulty account.

  7. Neural circuits via which single prolonged stress exposure leads to fear extinction retention deficits.

    PubMed

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; Keller, Samantha M; DePietro, Thomas

    2016-12-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions critical for extinction retention (i.e., fear extinction circuit). These were the ventral hippocampus (vHipp), dorsal hippocampus (dHipp), basolateral amygdala (BLA), prelimbic cortex (PL), and infralimbic cortex (IL). SPS or control rats were fear conditioned then subjected to extinction training and testing. Subsets of rats were euthanized after extinction training, extinction testing, or immediate removal from the housing colony (baseline condition) to assay c-Fos levels (measure of neural activity) in respective brain region. SPS induced extinction retention deficits. During extinction training SPS disrupted enhanced IL neural activity and inhibited BLA neural activity. SPS also disrupted inhibited BLA and vHipp neural activity during extinction testing. Statistical analyses suggested that SPS disrupted functional connectivity within the dHipp during extinction training and increased functional connectivity between the BLA and vHipp during extinction testing. Our findings suggest that SPS induces extinction retention deficits by disrupting both excitatory and inhibitory changes in neural activity within the fear extinction circuit and inducing changes in functional connectivity within the Hipp and BLA. © 2016 Knox et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Inhibitory Control as a Moderator of Threat-related Interference Biases in Social Anxiety

    PubMed Central

    Gorlin, Eugenia I.; Teachman, Bethany A.

    2014-01-01

    Prior findings are mixed regarding the presence and direction of threat-related interference biases in social anxiety. The current study examined general inhibitory control (IC), measured by the classic color-word Stroop, as a moderator of the relationship between both threat interference biases (indexed by the emotional Stroop) and several social anxiety indicators. High socially anxious undergraduate students (N=159) completed the emotional and color-word Stroop tasks, followed by an anxiety-inducing speech task. Participants completed measures of trait social anxiety, state anxiety before and during the speech, negative task-interfering cognitions during the speech, and overall self-evaluation of speech performance. Speech duration was used to measure behavioral avoidance. In line with hypotheses, IC moderated the relationship between emotional Stroop bias and every anxiety indicator (with the exception of behavioral avoidance), such that greater social-threat interference was associated with higher anxiety among those with weak IC, whereas lesser social-threat interference was associated with higher anxiety among those with strong IC. Implications for the theory and treatment of threat interference biases in socially anxious individuals are discussed. PMID:24967719

  9. The temperature and ion energy dependence of deuterium retention in lithium films

    NASA Astrophysics Data System (ADS)

    Buzi, Luxherta; Koel, Bruce E.; Skinner, Charles H.

    2016-10-01

    Lithium conditioning of plasma facing components in magnetic fusion devices has improved plasma performance and lowered hydrogen recycling. For applications of lithium in future high heat flux and long pulse duration machines it is important to understand and parameterize deuterium retention in lithium. This work presents surface science studies of deuterium retention in lithium films as a function of surface temperature, incident deuterium ion energy and flux. Initial experiments are performed on thin (3-30 ML) lithium films deposited on a single crystal molybdenum substrate to avoid effects due to grain boundaries, intrinsic defects and impurities. A monoenergetic and mass-filtered deuterium ion beam was generated in a differentially pumped Colutron ion gun. Auger electron spectroscopy and X-ray photoelectron spectroscopy were used to identify the elemental composition and temperature programmed desorption was used to measure the deuterium retention under the different conditions. Support was provided through DOE Contract Number DE-AC02-09CH11466.

  10. Family Responsive Policies and Employee Retention Following Childbirth.

    ERIC Educational Resources Information Center

    Glass, Jennifer L.; Riley, Lisa

    1998-01-01

    Among 324 employed women in Indiana, followed from pregnancy through 12 months postpartum, job attrition after childbirth was significantly decreased by employer policies, particularly length of maternity leave and ability to avoid mandatory overtime upon return, and was also decreased by supervisor and coworker social support, greater educational…

  11. First Year Experience for At-Risk College Students

    ERIC Educational Resources Information Center

    Connolly, Sara; Flynn, Ellen E.; Jemmott, Jill; Oestreicher, Edina

    2017-01-01

    In this study, we explored whether a uniquely designed First Year Experience (FYE) class for newly admitted at-risk college students would increase academic success; help students avoid academic probation; and increase retention for the following semester. Participants included 40 students (75% African Americans, 20% Hispanic Americans, and 5%…

  12. An Insurance Crisis Looms--Again.

    ERIC Educational Resources Information Center

    Henke, Cliff

    1993-01-01

    The insurance industry has experienced a round of claims costs as a result of recent natural disasters. These costs are passed on to customers. To avoid higher premiums, student-transportation systems can take the following money-saving steps: raise the deductible; beef up driver training; focus on driver retention; and get the fleet's loss…

  13. Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy.

    PubMed

    Mei, Ling; Liu, Yayuan; Rao, Jingdong; Tang, Xian; Li, Man; Zhang, Zhirong; He, Qin

    2018-05-30

    Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were achieved because of the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T cell responses protected mice from tumor recurrence.

  14. [Sacral nerve stimulation in the treatment of the lower urinary tract function disorders].

    PubMed

    Miotła, Paweł; Kulik-Rechberger, Beata; Skorupski, Paweł; Rechberger, Tomasz

    2011-11-01

    Functional disorders of the female lower urinary tract like urge incontinence, idiopathic urinary retention and symptoms of urgency-frequency occasionally do not respond properly to classical behavioral and pharmacological therapy Therefore, additional alternative therapies are needed to alleviate these bothersome symptoms. Sacral neuromodulation (SNS) utilize mild electrical pulses which activate or suppress neural reflexes responsible for voiding by stimulating the sacral nerves that innervate the bladder, external urethral sphincter and pelvic floor muscles. The exact mechanism of SNS action is not yet fully understood but it is assumed that it influences the neuroaxis at different levels of the central nervous system and restores the balance between inhibitory and activatory control over the voiding reflex. There is numerous evidence on the success of SNS not only in the treatment of refractory urge incontinence in adult and children but also in idiopathic urinary retention and symptoms of urgency-frequency

  15. The Extracellular Protease Matrix Metalloproteinase-9 Is Activated by Inhibitory Avoidance Learning and Required for Long-Term Memory

    ERIC Educational Resources Information Center

    Nagy, Vanja; Bozdagi, Ozlem; Huntley, George W.

    2007-01-01

    Matrix metalloproteinases (MMPs) are a family of extracellularly acting proteolytic enzymes with well-recognized roles in plasticity and remodeling of synaptic circuits during brain development and following brain injury. However, it is now becoming increasingly apparent that MMPs also function in normal, nonpathological synaptic plasticity of the…

  16. Intra-Amygdala Injections of CREB Antisense Impair Inhibitory Avoidance Memory: Role of Norepinephrine and Acetylcholine

    ERIC Educational Resources Information Center

    Canal, Clinton E.; Chang, Qing; Gold, Paul E.

    2008-01-01

    Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed…

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ogawa, E.; Suzuki, S.; Tsuzuki, H.

    Mice were subcutaneoulsy injected with Sr/sup 90/ or Sr/sup 85/, and effects of various drugs on their 3-day excretion and retention on the 4th day were investigated. Among chelating agents, NaCa citrate, NaMg citrate, NaSr citrate, Achromycin (or tetracycline), and aspartic MgK (alone or in combination with NH/sub 4/Cl) displayed Sr-eliminating effects. ATP increased only the excretion without diminishing the retention in bone. EDTA, DTPA, BADE, tricarballylate, Na citrate and NaPb citrate were not effective. Among salts, Mg salt, sulfite, and thiosulfate were effective in eliminating Sr. The last exerted a greater effect when given concurrently with Mg, Ca, ormore » Sr salt. Ca and Sr salt exerted no effect, and ammonium chloride promoted only urinary secretion, not extending to local or total excretion. Such salts as induce alkalosis conversely exerted inhibitory effects. Among hormones, glucocorticoids had Sreliminating effects. TSH was effective, and antithyroidal drugs conversely seemed to have excretion-diminishing effects. Among vitamins, cocarboxylase increased Sr excretion, but did not decrease the retention in bone. Also metabolic inhibitors were ineffective, and NaF conversely increased bone deposition of Sr. Among diuretics, SHdrugs, and weak chelating agents, there were no effective drugs. (JAIF)« less

  18. Requirement of NF-kappa B Activation in Different Mice Brain Areas during Long-Term Memory Consolidation in Two Contextual One-Trial Tasks with Opposing Valences

    PubMed Central

    Salles, Angeles; Krawczyk, Maria del C.; Blake, Mariano; Romano, Arturo; Boccia, Mariano M.; Freudenthal, Ramiro

    2017-01-01

    NF-kappa B is a transcription factor whose activation has been shown to be necessary for long-term memory consolidation in several species. NF-kappa B is activated and translocates to the nucleus of cells in a specific temporal window during consolidation. Our work focuses on a one trial learning tasks associated to the inhibitory avoidance (IA) setting. Mice were trained either receiving or not a footshock when entering a dark compartment (aversive vs. appetitive learning). Regardless of training condition (appetitive or aversive), latencies to step-through during testing were significantly different to those measured during training. Additionally, these testing latencies were also different from those of a control group that only received a shock unrelated to context. Moreover, nuclear NF-kappa B DNA-binding activity was augmented in the aversive and the appetitive tasks when compared with control and naïve animals. NF-kappa B inhibition by Sulfasalazine injected either in the Hippocampus, Amygdala or Nucleus accumbens immediately after training was able to impair retention in both training versions. Our results suggest that NF-kappa B is a critical molecular step, in different brain areas on memory consolidation. This was the case for both the IA task and also the modified version of the same task where the footshock was omitted during training. This work aims to further investigate how appetitive and aversive memories are consolidated. PMID:28439227

  19. Neural control of renal function.

    PubMed

    Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

    2011-04-01

    The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

  20. Passive avoidance and complex maze learning in the senescence accelerated mouse (SAM): age and strain comparisons of SAM P8 and R1.

    PubMed

    Spangler, Edward L; Patel, Namisha; Speer, Dorey; Hyman, Michael; Hengemihle, John; Markowska, Alicja; Ingram, Donald K

    2002-02-01

    Two strains of the senescence accelerated mouse, P8 and R1,were tested in footshock-motivated passive avoidance (PA; P8, 3-21 months; R1, 3-24 months) and 14-unit T-maze (P8 and R1, 9, and 15 months) tasks. For PA, entry to a dark chamber from a lighted chamber was followed by a brief shock. Latency to enter the dark chamber 24 hours later served as a measure of retention. Two days of active avoidance training in a straight runway preceded 2 days (8 trials/day) of testing in the 14-unit T-maze. For PA retention, older P8 mice entered the dark chamber more quickly than older R1 mice, whereas no differences were observed between young P8 or R1 mice. In the 14-unit T-maze, age-related learning performance deficits were reflected in higher error scores for older mice. P8 mice were actually superior learners; that is, they had lower error scores compared with those of age-matched R1 counterparts. Although PA learning results were in agreement with other reports, results obtained in the 14-unit T-maze were not consistent with previous reports of learning impairments in the P8 senescence accelerated mouse.

  1. Immediate, non-submerged, root-analogue zirconia implant in single tooth replacement.

    PubMed

    Pirker, W; Kocher, A

    2008-03-01

    This report demonstrates the successful clinical use of a modified root-analogue zirconia implant for immediate single tooth replacement. A right maxillary premolar was removed and a custom-made, root-analogue, roughened zirconia implant with macro-retentions in the interdental space was fabricated and placed into the extraction socket 4 days later. Four months after root implantation a composite crown was cemented. No complications occurred during the healing period. An excellent esthetic and functional result was achieved with the composite crown. No clinically noticeable bone resorption or soft-tissue recession was observed at 26 months follow up. Significant modifications such as macro-retentions seem to indicate that primary stability and excellent osseointegration of immediate root-analogue zirconia implants can be achieved, while preventing unesthetic bone resorption. The macro-retentions must be limited to the interdental space to avoid fracture of the thin buccal cortex. This successful case warrants further clinical research in well controlled trials.

  2. Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control

    ERIC Educational Resources Information Center

    Howard, Steven J.; Okely, Anthony D.

    2015-01-01

    Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted…

  3. Avoiding unwanted vicinity effects with attract-and-kill tactics for harlequin bug, Murgantia histrionica (Hahn)

    USDA-ARS?s Scientific Manuscript database

    In the development of an attract-and-kill approach for the management of harlequin bug (HB), Murgantia histrionica (Hahn), we evaluated attraction and retention of HB by pheromone-baited traps in the field. In release-recapture and on-farm experiments, traps combining collard plants with commercial ...

  4. Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus.

    PubMed

    McIntyre, Christa K; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D; Steward, Oswald; Guzowski, John F; McGaugh, James L

    2005-07-26

    Activation of beta-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the beta-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance.

  5. Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus

    PubMed Central

    McIntyre, Christa K.; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D.; Steward, Oswald; Guzowski, John F.; McGaugh, James L.

    2005-01-01

    Activation of β-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the β-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance. PMID:16020527

  6. Multiple trial inhibitory avoidance acquisition and retrieval are resistant to chronic stress.

    PubMed

    Raya, J; Girardi, C E N; Esumi, L A; Ferreira, L B T; Hipólide, D C

    2018-02-01

    Chronic mild stress (CMS) is a widely accepted animal model relevant to depression that among other consequences, is chiefly known to induce anhedonia, often assessed as decreased preference for sucrose solution. CMS is also known to affect cognition, particularly memory tasks. In this study we have employed the multiple-trial inhibitory avoidance memory task (MTIA) to assess CMS effects on memory acquisition and retrieval. MTIA consists of repeated exposures to the unconditioned stimulus until a learning criterion is reached. Wistar rats underwent CMS for 5 weeks, and sucrose consumption was assessed once a week. At the end of CMS, animals were evaluated in the MTIA task. Overall decreased sucrose solution preference was highly variable. Further analyses showed that a subset of animals expressed resilience while another subset was sensitive to stress. CMS did not affect the number of acquisition sessions before reaching criterion or retrieval latency of MTIA task in neither sensitive nor resilient groups. Although tasks that assess learning ability in animal models relevant to depression indicate cognitive deficits, the ability to learn the association between compartment crossing and the aversive electric foot shock, which is strongly dependent on emotional aspects, was intact. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Neonatal Escherichia coli K1 meningitis causes learning and memory impairments in adulthood.

    PubMed

    Barichello, Tatiana; Dagostim, Valdemira S; Generoso, Jaqueline S; Simões, Lutiana R; Dominguini, Diogo; Silvestre, Cintia; Michels, Monique; Vilela, Márcia Carvalho; Jornada, Luciano K; Comim, Clarissa M; Dal-Pizzol, Felipe; Teixeira, Antonio Lucio; Quevedo, João

    2014-07-15

    Neonatal Escherichia coli meningitis continues to be an important cause of mortality and morbidity in newborns worldwide. The aim of this study was to investigate the cytokines/chemokines, brain-derived neurotrophic factor (BDNF) levels, blood-brain barrier integrity in neonatal rats following E. coli K1 experimental meningitis infection and subsequent behavioural parameters in adulthood. In the hippocampus, interleukin increased at 96 h, IL-6 at 12, 48 and 96 h, IL-10 at 96 h, cytokine-induced neutrophil chemoattractant-1 at 6, 12, 24, 48 and 96 h, and BDNF at 48 and 96 h. In the cerebrospinal fluid, tumour necrosis factor alpha levels increased at 6, 12, 24, 48 and 96 h. The BBB breakdown occurred at 12 h in the hippocampus, and at 6h in the cortex. We evaluated behavioural parameters in adulthood: habituation to the open-field, step-down inhibitory avoidance, object recognition, continuous multiple-trials step-down inhibitory avoidance and forced swimming tasks. In adulthood, the animals showed habituation and aversive memory impairment. The animals needed a significant increase in the number of training periods to learn and not had depressive-like symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise.

    PubMed

    García-Capdevila, Sílvia; Portell-Cortés, Isabel; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David

    2009-09-14

    The effect of long-term voluntary exercise (running wheel) on anxiety-like behaviour (plus maze and open field) and learning and memory processes (object recognition and two-way active avoidance) was examined on Wistar rats. Because major individual differences in running wheel behaviour were observed, the data were analysed considering the exercising animals both as a whole and grouped according to the time spent in the running wheel (low, high, and very-high running). Although some variables related to anxiety-like behaviour seem to reflect an anxiogenic compatible effect, the view of the complete set of variables could be interpreted as an enhancement of defensive and risk assessment behaviours in exercised animals, without major differences depending on the exercise level. Effects on learning and memory processes were dependent on task and level of exercise. Two-way avoidance was not affected either in the acquisition or in the retention session, while the retention of object recognition task was affected. In this latter task, an enhancement in low running subjects and impairment in high and very-high running animals were observed.

  9. A Wortmannin-Cetuximab As A Double Drug

    PubMed Central

    Smith, R. Adam; Yuan, Hushan; Weissleder, Ralph; Cantley, Lewis C.; Josephson, Lee

    2012-01-01

    Double drugs are obtained when two pharmacologically active entities are covalently joined to improve potency. We conjugated the viridin Wm with a self-activating linkage to cetuximab and demonstrated the retention of immunoreactivity by the conjugate. Though cetuximab lacked a growth inhibitory activity against A549 cells, the Wmcetuximab conjugate had an anti-proliferative IC50 of 155 nM in vitro. The chemistry of attaching a self-releasing Wm to clinically approved antibodies is general and, in selected instances, may yield antibody-based double drugs with improved efficacy. PMID:19883074

  10. Nursing practice environment: a strategy for mental health nurse retention?

    PubMed

    Redknap, Robina; Twigg, Di; Rock, Daniel; Towell, Amanda

    2015-06-01

    Historically, mental health services have faced challenges in their ability to attract and retain a competent nursing workforce in the context of an overall nursing shortage. The current economic downturn has provided some respite; however, this is likely to be a temporary reprieve, with significant nursing shortages predicted for the future. Mental health services need to develop strategies to become more competitive if they are to attract and retain skilled nurses and avoid future shortages. Research demonstrates that creating and maintaining a positive nursing practice environment is one such strategy and an important area to consider when addressing nurse retention. This paper examines the impact the nursing practice environment has on nurse retention within the general and mental health settings. Findings indicate, that while there is a wealth of evidence to support the importance of a positive practice environment on nurse retention in the broader health system, there is little evidence specific to mental health. Further research of the mental health practice environment is required. © 2015 Australian College of Mental Health Nurses Inc.

  11. Difference equation model for isothermal gas chromatography expresses retention behavior of homologues of n-alkanes excluding the influence of holdup time

    PubMed Central

    Wu, Liejun; Chen, Yongli; Caccamise, Sarah A.L.; Li, Qing X.

    2012-01-01

    A difference equation (DE) model is developed using the methylene retention increment (Δtz) of n-alkanes to avoid the influence of gas holdup time (tM). The effects of the equation orders (1st–5th) on the accuracy of a curve fitting show that a linear equation (LE) is less satisfactory and it is not necessary to use a complicated cubic or higher order equation. The relationship between the logarithm of Δtz and the carbon number (z) of the n-alkanes under isothermal conditions closely follows the quadratic equation for C3–C30 n-alkanes at column temperatures of 24–260 °C. The first and second order forward differences of the expression (Δlog Δtz and Δ2log Δtz, respectively) are linear and constant, respectively, which validates the DE model. This DE model lays a necessary foundation for further developing a retention model to accurately describe the relationship between the adjusted retention time and z of n-alkanes. PMID:22939376

  12. Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

    PubMed

    Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

    2003-05-01

    We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

  13. A subliminal inhibitory mechanism for the negative compatibility effect: a continuous versus threshold mechanism.

    PubMed

    Liu, Peng; Chen, Xuhai; Dai, Dongyang; Wang, Yongchun; Wang, Yonghui

    2014-07-01

    The current study investigated the mechanism underlying subliminal inhibition using the negative compatibility effect (NCE) paradigm. We hypothesized that a decrease in prime activation affects the subsequent inhibitory process, delaying onset of inhibition and reducing its strength. Two experiments tested this hypothesis using arrow stimuli as primes and targets. Two different irrelevant masks (i.e., a mask sharing no prime features) were presented in succession in each trial to not only ensure that primes were processed subliminally, but also avoid feature updating between primes and masks. Prime/target compatibility and prime background density were manipulated in Experiment 1. Results showed that under subliminal inhibitory condition, the NCE disappears when the density increases (i.e., pixel density in the prime's background of 25 %) in Experiment 1. However, when we fixed the prime's background at the density of 25 % and manipulated prime/target compatibility as well as inter-stimuli-interval (ISI) between mask and target in Experiment 2, behavioral results showed marginally significant NCEs in the 150-ms ISI condition. Electrophysiological evidence showed the lateralized readiness potential for compatible trials was significantly more positive than that for incompatible trials during the two consecutive time windows (i.e., 400-450 and 450-500 ms) in the 150-ms ISI condition. In addition, the NCE size was significant smaller in Experiment 2 than in Experiment 1. All of the results support predictions of the continuous subliminal inhibitory mechanism hypothesis which posits that decreases in prime activation strength lead to delay in inhibitory onset and decline in inhibitory strength.

  14. Nitric oxide in the dorsal hippocampal area is involved on muscimol state-dependent memory in the step-down passive avoidance test.

    PubMed

    Jafari-Sabet, Majid; Khodadadnejad, Mohammad-Amin; Ghoraba, Saeed; Ataee, Ramin

    2014-02-01

    In the present study, the effects of intra-dorsal hippocampal (intra-CA1) injections of nitric oxide (NO) agents on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice. Post-training intra-CA1 administration of a GABAA receptor agonist, muscimol (0.05 and 0.1 μg/mouse) dose dependently induced impairment of memory retention. Pre-test injection of muscimol (0.05 and 0.1 μg/mouse) induced state-dependent retrieval of the memory acquired under post-training muscimol (0.1 μg/mouse, intra-CA1) influence. Pre-test injection of a NO precursor, L-arginine (1 and 2 μg/mouse, intra-CA1) improved memory retention, although the low dose of the drug (0.5 μg/mouse) did not affect memory retention. Pre-test injection of an inhibitor of NO-synthase, L-NAME (0.5 and 1 μg/mouse, intra-CA1) impaired memory retention, although the low dose of the drug (0.25 μg/mouse) did not affect memory retention. In other series of experiments, pre-test intra-CA1 injection of L-arginine (0.25 and 0.5 μg/mouse) 5 min before the administration of muscimol (0.1 μg/mouse, intra-CA1) dose dependently inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of L-arginine (0.125, 0.25 and 0.5 μg/mouse) by itself cannot affect memory retention. Pre-test intra-CA1 injection of L-NAME (0.25 μg/mouse, intra-CA1) reversed the memory impairment induced by post-training administration of muscimol (0.1 μg/mouse, intra-CA1). Moreover, pre-test administration of L-NAME (0.125 and 0.25 μg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 μg/mouse, intra-CA1) significantly restored the retrieval and induced muscimol state-dependent memory. Pre-test intra-CA1 administration of L-NAME (0.0625, 0.125 and 0.25 μg/mouse) by itself cannot affect memory retention. It may be suggested that the nitric oxide in the dorsal hippocampal area play an important role in muscimol state-dependent memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Facilitation by 8-OH-DPAT of passive avoidance performance in rats after inactivation of 5-HT1A receptors

    PubMed Central

    Otano, Ana; García-Osta, Ana; Ballaz, Santiago; Frechilla, Diana; Del Río, Joaquín

    1999-01-01

    Pretraining administration of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT 0.1 mg kg−1), a 5-HT1A receptor agonist, or buspirone (1 mg kg−1), a 5-HT1A receptor partial agonist, markedly impaired passive avoidance retention in rats 24 h later. The effect of 8-OH-DPAT was prevented by the 5-HT1A receptor antagonists, NAN-190 and WAY-100635, at doses without any intrinsic effect.N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ 10 mg kg−1), an alkylating agent that inactivates different G-protein coupled receptors, impaired retention performance when given 48 h pretraining. The disruptive effect of EEDQ was reversed by 8-OH-DPAT or buspirone, given 30 min before training.Non-specific actions did not account for 8-OH-DPAT-induced reversal of the EEDQ effect since no significant difference in locomotor activity or in pain threshold was found between rats receiving EEDQ or EEDQ+8-OH-DPAT.When NAN-190 (1 mg kg−1) or WAY-100635 (0.5 mg kg−1) were given before 8-OH-DPAT to EEDQ-pretreated animals, the reversal by 8-OH-DPAT of EEDQ-induced retention impairment was still more pronounced. However, no EEDQ reversal by 8-OH-DPAT was found when 5-HT1A receptors were protected by WAY-100635 (10 mg kg−1) 30 min before EEDQ.In the hippocampus of EEDQ-treated rats, 5-HT7 receptors were less inactivated than 5-HT1A receptors and significant increases were found in 5-HT1A but not in 5-HT7 receptor mRNA levels. Ritanserin and methiothepin (10 mg kg−1 each), antagonists with higher affinity at 5-HT7 than at 5-HT1A receptors, prevented the retention impairment induced by EEDQ but did not significantly protect against 5-HT7 receptor inactivation.The results indicate that the facilitatory effect of 8-OH-DPAT is not mediated through 5-HT1A receptors and suggest that other 8-OH-DPAT-sensitive receptors could be involved in the dual effect of 8-OH-DPAT on passive avoidance performance in rats. PMID:10588924

  16. Memory effects of Aronia melanocarpa fruit juice in a passive avoidance test in rats.

    PubMed

    Valcheva-Kuzmanova, Stefka V; Eftimov, Miroslav Tz; Tashev, Roman E; Belcheva, Iren P; Belcheva, Stiliana P

    2014-01-01

    To study the effect of Aronia melanocarpa fruit juice on memory in male Wistar rats. The juice was administered orally for 7, 14, 21 and 30 days at doses of 2.5 ml/kg, 5 ml/kg and 10 ml/kg. Memory was assessed in the one-way passive avoidance task (step through) which consisted of one training session and two retention tests (3 hours and 24 hours after training). The variables measured were the latency time to step into the dark compartment of the apparatus and the learning criterion (remaining in the illuminated compartment for at least 180 sec). Oral administration of Aronia melanocarpa fruit juice for 7 and 14 days resulted in a dose-dependent tendency to increase the latency time and the learning criterion compared to saline-treated controls but the effect failed to reach statistical significance. After 21 days of treatment, the juice dose-dependently prolonged the latency time at the retention tests, the effect being significant at doses of 5 ml/kg and 10 ml/kg. Applied for 30 days, the juice in all the tested doses increased significantly the latency time at the retention tests and the dose of 10 ml/kg significantly increased the percentage of rats reaching the learning criterion. These findings suggest that Aronia melanocarpa fruit juice could improve memory in rats. The effect is probably due to the polyphenolic ingredients of the juice which have been shown to be involved in learning and memory processes.

  17. The effects of green Ocimum basilicum hydroalcoholic extract on retention and retrieval of memory in mice

    PubMed Central

    Sarahroodi, Shadi; Esmaeili, Somayyeh; Mikaili, Peyman; Hemmati, Zahra; Saberi, Yousof

    2012-01-01

    The purpose of this study was evaluation of green Ocimum basilicum (sweet basil) hydroalcoholic extract on memory retention and retrieval of mice by using passive avoidance apparatus. For this purpose, after weighting, coding and classifying the mice, they were grouped (n = 8) as follow as: test groups (electric shock plus sweet basil extract by doses: 100, 200, 400 and 800 mg/kg, i.p.), control group (Only electric shock) and blank group (electric shock plus normal saline). In all mentioned groups delay time of leaving the platform for both retention and retrieval test of memory was measured. In retention test, sweet basil extract was administered immediately after receiving electric shock and in retrieval test it was administered 24 hours after receiving electric shock. The results indicated that hydroalcoholic extract of green Ocimum basilicum significantly (P < 0.05) increased memory retention. The best response was achieved with 400 mg/Kg of the extract. Also, results showed that sweet basil extract significantly (P < 0.05) increased memory retrieval and the best result was achieved with 400 mg/Kg too. It can be concluded that memory enhancing effects of green Ocimum basilicum is because of antioxidant activity of flavonoids, tannins and terpenoids. PMID:23661866

  18. Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.

    PubMed

    Bour, Alexandra; Grootendorst, Jeannette; Vogel, Elise; Kelche, Christian; Dodart, Jean-Cosme; Bales, Kelly; Moreau, Pierre-Henri; Sullivan, Patrick M; Mathis, Chantal

    2008-11-21

    Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cognitive decline.

  19. Chronic cyanidin-3-glucoside administration improves short-term spatial recognition memory but not passive avoidance learning and memory in streptozotocin-diabetic rats.

    PubMed

    Nasri, Sima; Roghani, Mehrdad; Baluchnejadmojarad, Tourandokht; Balvardi, Mahboubeh; Rabani, Tahereh

    2012-08-01

    This research study was conducted to evaluate the efficacy of chronic cyanidin-3-glucoside (C3G) on alleviation of learning and memory deficits in diabetic rats as a result of the observed antidiabetic and antioxidant activity of C3G. Male Wistar rats were divided into control, diabetic, C3G-treated-control and -diabetic groups. The C3G was administered i.p. at a dose of 10 mg/kg on alternate days for eight weeks. For evaluation of learning and memory, initial latency (IL) and step-through latency (STL) were determined at the end of study using passive avoidance test. Meanwhile, spatial recognition memory was assessed as alternation in the Y-maze task. Oxidative stress markers in brain tissue were also measured. It was found that the alternation score of the diabetic rats was lower than that of control (p < 0.01) and C3G-treated diabetic rats showed a higher alternation score as compared to diabetic group (p < 0.05). Diabetic rats also developed a significant impairment in retention and recall in passive avoidance test (p < 0.01) and C3G treatment of diabetic rats did not produce any significant improvement. Meanwhile, increased level of malondialdehyde (MDA) in diabetic rats was significantly reduced following C3G treatment (p < 0.05). Taken together, chronic C3G could improve short-term spatial recognition memory disturbance in the Y-maze test but not retention and recall capability in passive avoidance test in STZ-diabetic rats. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Retention of long-term interim restorations with sodium fluoride enriched interim cement

    NASA Astrophysics Data System (ADS)

    Strash, Carolyn

    Purpose: Interim fixed dental prostheses, or "provisional restorations", are fabricated to restore teeth when definitive prostheses are made indirectly. Patients undergoing extensive prosthodontic treatment frequently require provisionalization for several months or years. The ideal interim cement would retain the restoration for as long as needed and still allow for ease of removal. It would also avoid recurrent caries by preventing demineralization of tooth structure. This study aims to determine if adding sodium fluoride varnish to interim cement may assist in the retention of interim restorations. Materials and methods: stainless steel dies representing a crown preparation were fabricated. Provisional crowns were milled for the dies using CAD/CAM technology. Crowns were provisionally cemented onto the dies using TempBond NE and NexTemp provisional cements as well as a mixture of TempBond NE and Duraphat fluoride varnish. Samples were stored for 24h then tested or thermocycled for 2500 or 5000 cycles before being tested. Retentive strength of each cement was recorded using a universal testing machine. Results: TempBond NE and NexTemp cements performed similarly when tested after 24h. The addition of Duraphat significantly decreased the retention when added to TempBond NE. NexTemp cement had high variability in retention over all tested time periods. Thermocycling for 2500 and 5000 cycles significantly decreased the retention of all cements. Conclusions: The addition of Duraphat fluoride varnish significantly decreased the retention of TempBond NE and is therefore not recommended for clinical use. Thermocycling significantly reduced the retention of TempBond NE and NexTemp. This may suggest that use of these cements for three months, as simulated in this study, is not recommended.

  1. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats.

    PubMed

    Yildiz Akar, Furuzan; Ulak, Guner; Tanyeri, Pelin; Erden, Faruk; Utkan, Tijen; Gacar, Nejat

    2007-10-01

    The role of nitric oxide (NO) on cognitive performance in a modified elevated plus-maze (mEPM) and passive-avoidance (PA) task was investigated by using the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI) and an NO precursor l-arginine. The interaction between the activation of N-methyl-d-aspartate (NMDA) receptors and NO synthesis on memory retention was also studied. 7-NI, l-arginine or MK-801, a non-competitive NMDA receptor antagonist were injected intraperitoneally (i.p) to male Wistar rats 30 min before the first training session of the PA test or 30 min before on the first day testing (acquisition session) of mEPM task. Transfer latency, the time rat took to move from the open arm to the enclosed arm, was used as an index of learning and memory in a mEPM test. The retention session was performed 24 h after the acquisition one. In the PA task, the retention test was carried out 24 h after training and reduction of retention latency was used to evaluate the acquisition of learning and memory. Blood glucose level and locomotor activity of the rats was also evaluated. 7-NI (10, 20, 25, 50 mg/kg) and MK-801 (0.15 mg/kg) significantly prolonged the transfer latency on retention session in a mEPM test and shortened step-through latency in PA test. 7-NI-induced impairment in memory and learning was partly reversed by l-arginine (200 mg/kg), a competitive substrate for NOS. However subeffective doses of 7-NI (5 mg/kg) and MK-801 (0.075 mg/kg) given in combination significantly impaired plus-maze and PA performances in rats. Thus NMDA receptor mediated NO pathways may be implicated in the PA and mEPM behaviours in rats. Since 7-NI does not affect blood pressure and did not alter blood glucose level and locomotor activity in conscious rats, 7-NI-induced impairment of memory is not due to either hypertension, changes in blood glucose level or effects on locomotor activity.

  2. Procoagulant Platelets Form an α-Granule Protein-covered “Cap” on Their Surface That Promotes Their Attachment to Aggregates*

    PubMed Central

    Abaeva, Anastasia A.; Canault, Matthias; Kotova, Yana N.; Obydennyy, Sergey I.; Yakimenko, Alena O.; Podoplelova, Nadezhda A.; Kolyadko, Vladimir N.; Chambost, Herve; Mazurov, Aleksei V.; Ataullakhanov, Fazoil I.; Nurden, Alan T.; Alessi, Marie-Christine; Panteleev, Mikhail A.

    2013-01-01

    Strongly activated “coated” platelets are characterized by increased phosphatidylserine (PS) surface expression, α-granule protein retention, and lack of active integrin αIIbβ3. To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the α-granule protein “coat.” Confocal microscopy revealed that fibrin(ogen) and thrombospondin colocalized as “cap,” a single patch on the PS-positive platelet surface. In aggregates, the cap was located at the point of attachment of the PS-positive platelets. Without fibrin(ogen) retention, their ability to be incorporated in aggregates was drastically reduced. The surface fibrin(ogen) was strongly decreased in the presence of a fibrin polymerization inhibitor GPRP and also in platelets from a patient with dysfibrinogenemia and a fibrinogen polymerization defect. In contrast, a fibrinogen-clotting protease ancistron increased the amount of fibrin(ogen) and thrombospondin on the surface of the PS-positive platelets stimulated with collagen-related peptide. Transglutaminases are also involved in fibrin(ogen) retention. However, platelets from patients with factor XIII deficiency had normal retention, and a pan-transglutaminase inhibitor T101 had only a modest inhibitory effect. Fibrin(ogen) retention was normal in Bernard-Soulier syndrome and kindlin-3 deficiency, but not in Glanzmann thrombasthenia lacking the platelet pool of fibrinogen and αIIbβ3. These data show that the fibrin(ogen)-covered cap, predominantly formed as a result of fibrin polymerization, is a critical mechanism that allows coated (or rather “capped”) platelets to become incorporated into thrombi despite their lack of active integrins. PMID:23995838

  3. The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex.

    PubMed

    George, Sophie A; Rodriguez-Santiago, Mariana; Riley, John; Rodriguez, Elizabeth; Liberzon, Israel

    2015-01-01

    Post-traumatic stress disorder (PTSD) is a chronic, debilitating disorder. Only two pharmacological agents are approved for PTSD treatment, and they often do not address the full range of symptoms nor are they equally effective in all cases. Animal models of PTSD are critical for understanding the neurobiology involved and for identification of novel therapeutic targets. Using the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant excitatory neural transmission and glucocorticoid receptor (GR) upregulation in the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory abnormalities associated with PTSD. The objective of this study is to examine the potential protective effect of antiepileptic phenytoin (PHE) administration on SPS-induced extinction retention deficits and GR expression. Forty-eight SPS-treated male Sprague Dawley rats or controls were administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors; then, fear conditioning, extinction, and extinction retention were tested. Fear conditioning and extinction were unaffected by SPS or PHE, but SPS impaired extinction retention, and both doses of PHE rescued this impairment. Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE prevented SPS-induced GR upregulation in the mPFC. These data demonstrate that PHE administration can prevent the development of extinction retention deficits and upregulation of GR. PHE exerts inhibitory effects on voltage-gated sodium channels and decreases excitatory neural transmission via glutamate antagonism. If glutamate hyperactivity in the days following SPS contributes to SPS-induced deficits, then these data may suggest that the glutamatergic system constitutes a target for secondary prevention.

  4. Anisomycin Infused into the Hippocampus Fails to Block "Reconsolidation" but Impairs Extinction: The Role of Re-Exposure Duration

    ERIC Educational Resources Information Center

    McGaugh, James L.; Steward, Oswald; Power, Ann E.; Berlau, Daniel J.

    2006-01-01

    Recent studies have reported new evidence consistent with the hypothesis that reactivating a memory by re-exposure to a training context destabilizes the memory and induces "reconsolidation." In the present experiments, rats' memory for inhibitory avoidance (IA) training was tested 6 h (Test 1), 2 d (Test 2), and 6 d (Test 3) after training. On…

  5. 46 CFR 120.340 - Cable and wiring requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... chafing and other damage. The use of plastic tie wraps must be limited to bundling or retention of... wires, rather than cables, are used in systems greater than 50 volts, the wire must be in conduit. (b... for the circuit in which they are used; (2) Be installed in a manner to avoid or reduce interference...

  6. Context specificity of inhibitory control in dogs

    PubMed Central

    MacLean, Evan L.; Hare, Brian A.

    2014-01-01

    Across three experiments, we explored whether a dog's capacity for inhibitory control is stable or variable across decision-making contexts. In the social task, dogs were first exposed to the reputations of a stingy experimenter that never shared food and a generous experimenter who always shared food. In subsequent test trials, dogs were required to avoid approaching the stingy experimenter when this individual offered (but withheld) a higher-value reward than the generous experimenter did. In the A-not-B task, dogs were required to inhibit searching for food in a previously rewarded location after witnessing the food being moved from this location to a novel hiding place. In the cylinder task, dogs were required to resist approaching visible food directly (because it was behind a transparent barrier), in favor of a detour reaching response. Overall, dogs exhibited inhibitory control in all three tasks. However, individual scores were not correlated between tasks, suggesting that context has a large effect on dogs' behavior. This result mirrors studies of humans, which have highlighted intra-individual variation in inhibitory control as a function of the decision-making context. Lastly, we observed a correlation between a subject's age and performance on the cylinder task, corroborating previous observations of age-related decline in dogs' executive function. PMID:23584618

  7. Effects of various treatments on the chemokinetic behavior of third-stage larvae of Strongyloides ratti on a sodium chloride gradient.

    PubMed

    Tobata-Kudo, H; Higo, H; Koga, M; Tada, I

    2000-11-01

    In observations of the movements of the infective third-stage larvae of a rodent parasitic nematode, Strongyloides ratti, on a sodium chloride gradient set up on agarose plates, two types of chemokinetic behavior were seen: a unidirectional avoidance movement on initial placement of the larvae in unfavorable environmental conditions and a random dispersal movement on their placement within an area of favorable conditions. Track patterns were straight in the avoidance movement but included multiple changes of direction and loops in the dispersal movement. In the present study we examined the interventional activity of treatment with various enzymes, lectins, and chemicals by analyzing the unidirectional avoidance movements of the larvae. We observed that beta-glucosidase, hyaluronidase, beta-galactosidase, trypsin, protease, lipase, phospholipase C, soybean agglutinin, wheat germ agglutinin, and spermidine exerted inhibitory actions on those movements, which may be guided by the chemosensory function of this nematode.

  8. Bitter-sweet processing in larval Drosophila.

    PubMed

    König, Christian; Schleyer, Michael; Leibiger, Judith; El-Keredy, Amira; Gerber, Bertram

    2014-07-01

    "Sweet-" and "bitter-" tasting substances distinctively support attractive and aversive choice behavior, respectively, and therefore are thought to be processed by distinct pathways. Interestingly, electrophysiological recordings in adult Drosophila suggest that bitter and salty tastants, in addition to activating bitter, salt, or bitter/salt sensory neurons, can also inhibit sweet-sensory neurons. However, the behavioral significance of such a potential for combinatorial coding is little understood. Using larval Drosophila as a study case, we find that the preference towards fructose is inhibited when assayed in the background of the bitter tastant quinine. When testing the influence of quinine on the preference to other, equally preferred sweet tastants, we find that these sweet tastants differ in their susceptibility to be inhibited by quinine. Such stimulus specificity argues that the inhibitory effect of quinine is not due to general effects on locomotion or nausea. In turn, not all bitter tastants have the same potency to inhibit sweet preference; notably, their inhibitory potency is not determined by the strength of the avoidance of them. Likewise, equally avoided concentrations of sodium chloride differ in their potency to inhibit sugar preference. Furthermore, Gr33a-Gal4-positive neurons, while being necessary for bitter avoidance, are dispensable for inhibition of the sweet pathway. Thus, interactions across taste modalities are behaviorally significant and, as we discuss, arguably diverse in mechanism. These results suggest that the coding of tastants and the organization of gustatory behavior may be more combinatorial than is generally acknowledged. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Retention of elemental mercury in fly ashes in different atmospheres

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    M.A. Lopez-Anton; M. Diaz-Somoano; M.R. Martinez-Tarazona

    2007-01-15

    Mercury is an extremely volatile element, which is emitted from coal combustion to the environment mostly in the vapor phase. To avoid the environmental problems that the toxic species of this element may cause, control technologies for the removal of mercury are necessary. Recent research has shown that certain fly ash materials have an affinity for mercury. Moreover, it has been observed that fly ashes may catalyze the oxidation of elemental mercury and facilitate its capture. However, the exact nature of Hg-fly ash interactions is still unknown, and mercury oxidation through fly ash needs to be investigated more thoroughly. Inmore » this work, the influence of a gas atmosphere on the retention of elemental mercury on fly ashes of different characteristics was evaluated. The retention capacity was estimated comparatively in inert and two gas atmospheres containing species present in coal gasification and coal combustion. Fly ashes produced in two pulverized coal combustion (PCC) plants, produced from coals of different rank (CTA and CTSR), and a fly ash (CTP) produced in a fluidized bed combustion (FBC) plant were used as raw materials. The mercury retention capacity of these fly ashes was compared to the retention obtained in different activated carbons. Although the capture of mercury is very similar in the gasification atmosphere and N{sub 2}, it is much more efficient in a coal combustion retention, being greater in fly ashes from PCC than those from FBC plants. 22 refs., 6 figs., 3 tabs.« less

  10. Sonographic findings in acute urinary retention secondary to retroverted gravid uterus: pathophysiology and preventive measures.

    PubMed

    Yang, J-M; Huang, W-C

    2004-05-01

    To explore the pathophysiology of acute urinary retention in women with a retroverted gravid uterus and to suggest measures to prevent its recurrence. In five women with a retroverted gravid uterus and acute urinary retention necessitating catheterization, the morphology of the genitourinary system was assessed by using transabdominal, transvaginal and introital sonography. In the supine resting position, the cervix was displaced superiorly and anteriorly by the impacted and retroverted uterus so that it compressed the lower bladder, leading to obstruction of the internal urethral orifice. The upper bladder extended superiorly and overlay the uterus. During straining, urethral motion was not limited and there was an average rotational angle of the bladder neck of 32 degrees, ranging from 21 degrees to 44 degrees. Increasing abdominal pressure further compressed the lower bladder. Measures suggested to the women for the prevention of urinary retention included limiting fluid intake before sleep, changing from the supine to the prone position before getting up and avoiding a Valsalva maneuver but performing a Credé maneuver during voiding. In all except one case these measures successfully prevented recurrence. Acute urinary retention secondary to a retroverted gravid uterus is caused by a displaced cervix compressing the lower bladder and interfering with drainage to the urethra. The urethra itself is not compressed or distorted. Understanding the pathophysiology of the lower urinary tract may allow maneuvers which prevent acute urinary retention. Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd.

  11. Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy.

    PubMed

    Zhu, Hai; Zhou, Binwei; Chan, Leung; Du, Yanxin; Chen, Tianfeng

    2017-01-01

    Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

  12. Neuromodulation by implant for treating lower urinary tract symptoms and dysfunction.

    PubMed

    Bemelmans, B L; Mundy, A R; Craggs, M D

    1999-08-01

    Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.

  13. Lesions of the lateral habenula facilitate active avoidance learning and threat extinction.

    PubMed

    Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek

    2017-02-01

    The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Soft Graphene Nanofibers Designed for the Acceleration of Nerve Growth and Development.

    PubMed

    Feng, Zhang-Qi; Wang, Ting; Zhao, Bin; Li, Jiacheng; Jin, Lin

    2015-11-04

    Soft graphene nanofibers with recoverable electrical conductivity and excellent physicochemical stability are prepared by a controlled assembly technique. By using the soft graphene nanofibers for cellular electrical stimulation, the common inhibitory effect of long-term electrical stimulation on nerve growth and development is avoided, which usually happens with traditional 2D conductive materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis

    PubMed Central

    da Silveira, Cinthia Cristina Sousa de Menezes; Fernandes, Luanna Melo Pereira; Silva, Mallone Lopes; Luz, Diandra Araújo; Gomes, Antônio Rafael Quadros; Machado, Christiane Schineider; de Lira, Tatiana Onofre; Ferreira, Antonio Gilberto

    2016-01-01

    Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP) rich in triterpenoids, primarily lupeol and β-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control), EEYP (1, 3, 10, and 30 mg/kg), or diazepam, fluoxetine, and caffeine (positive controls) 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product. PMID:27822336

  16. Treadmill performance of mice with cerebellar lesions: 1. Purkinje cell degeneration mutant mice.

    PubMed

    Le Marec, N; Lalonde, R

    1998-02-01

    The purpose of this study was to evaluate the sensorimotor skills of a spontaneous mouse mutant, Purkinje cell degeneration (PCD), marked by selective cerebellar cortical atrophy on a treadmill activated at 1 of 2 speeds and at 1 of 3 slopes, requiring forward movements to avoid footshocks. There was no difference in latencies before falling from the belt between PCD mutants and controls during acquisition. However, PCD mutants were impaired on the fast treadmill during retention, implicating the cerebellum in the memory of a motor skill. During acquisition of the slow treadmill task at the 2 lowest slopes of inclination, PCD mutants spent more time walking than controls, an indication of a decreased ability of coordinating whole body movements. The same pattern of higher walking time on the slow treadmill in PCD mutants was evident during retention. These results indicate that the cerebellar cortex is involved in the acquisition and the retention of a task requiring equilibrium.

  17. Modelling soil water retention using support vector machines with genetic algorithm optimisation.

    PubMed

    Lamorski, Krzysztof; Sławiński, Cezary; Moreno, Felix; Barna, Gyöngyi; Skierucha, Wojciech; Arrue, José L

    2014-01-01

    This work presents point pedotransfer function (PTF) models of the soil water retention curve. The developed models allowed for estimation of the soil water content for the specified soil water potentials: -0.98, -3.10, -9.81, -31.02, -491.66, and -1554.78 kPa, based on the following soil characteristics: soil granulometric composition, total porosity, and bulk density. Support Vector Machines (SVM) methodology was used for model development. A new methodology for elaboration of retention function models is proposed. Alternative to previous attempts known from literature, the ν-SVM method was used for model development and the results were compared with the formerly used the C-SVM method. For the purpose of models' parameters search, genetic algorithms were used as an optimisation framework. A new form of the aim function used for models parameters search is proposed which allowed for development of models with better prediction capabilities. This new aim function avoids overestimation of models which is typically encountered when root mean squared error is used as an aim function. Elaborated models showed good agreement with measured soil water retention data. Achieved coefficients of determination values were in the range 0.67-0.92. Studies demonstrated usability of ν-SVM methodology together with genetic algorithm optimisation for retention modelling which gave better performing models than other tested approaches.

  18. Spared Anterograde Memory for Shock-Probe Fear Conditioning After Inactivation of the Amygdala

    PubMed Central

    Lehmann, Hugo; Treit, Dallas; Parent, Marise B.

    2003-01-01

    Previous studies have shown that amygdala lesions impair avoidance of an electrified probe. This finding has been interpreted as indicating that amygdala lesions reduce fear. It is unclear, however, whether amygdala-lesioned rats learn that the probe is associated with shock. If the lesions prevent the formation of this association, then pretraining reversible inactivation of the amygdala should impair both acquisition and retention performance. To test this hypothesis, the amygdala was inactivated (tetrodotoxin; TTX; 1 ng/side) before a shock-probe acquisition session, and retention was tested 4 d later. The data indicated that, compared with rats infused with vehicle, rats infused with TTX received more shocks during the acquisition session, but more importantly, were not impaired on the retention test. In Experiment 2, we assessed whether the spared memory on the retention test was caused by overtraining during acquisition. We used the same procedure as in Experiment 1, with the exception that the number of shocks the rats received during the acquisition session was limited to four. Again the data indicated that amygdala inactivation did not impair performance on the retention test. These results indicate that amygdala inactivation does not prevent the formation of an association between the shock and the probe and that shock-probe deficits during acquisition likely reflect the amygdala's involvement in other processes. PMID:12888544

  19. Combination prosthetic design providing a superior retention for mid-facial defect rehabilitation: A Case Report

    PubMed Central

    Nilanonth, Supassra; Shakya, Prana; Srithavaj, Theerathavaj

    2017-01-01

    Large maxillofacial defects from malignant tumor treatment are rarely rehabilitated by surgical reconstruction alone. Ameloblastic carcinoma, a rare aggressive odontogenic malignant tumor, requires wide surgical excision to gain a tumor-free margin. In the post-surgical defect, prosthetic rehabilitation is the treatment of choice to restore function and esthetics. Moreover, an intra-oral prosthesis such as an obturator restores speech, mastication and deglutition. Retention of the obturator is a major problem while rehabilitating large defects. The existing anatomical structures from the defect with the help of magnet attachments are suitable to enhance retention, stability and support of the prostheses. This case report presents a patient with an intraoral and extra-oral combination defect following surgical resection of ameloblastic carcinoma and describes the prosthetic techniques and design considerations for a magnet-retained obturator and mid-facial prosthesis. An implant-retained mid-facial prosthesis was fabricated. The retention of combined prostheses was obtained from the remaining right posterior teeth only. The patient had an unfavorable defect due to the large size and presence of scar contracture that vertically tends to dislodge the obturator. Magnet attachments were used to combine the facial and oral prosthesis, minimize the vertical dislodging forces and enhance retention. In addition, the retention was also gained from the scar band at lower border of mid-facial defect that avoided the need for more implants surgery. Magnet attachment with anatomical structure of the mid-facial defect provides an acceptable means of retention in large extraoral-intraoral combinations defects, improving the function, esthetic and the patients’ quality of life. Key words:Mid-facial prosthesis, obturator, magnet attachment, maxillectomy. PMID:28469829

  20. Effect of Lactobacillus plantarum and chitosan in the reduction of browning of pericarp Rambutan (Nephelium lappaceum).

    PubMed

    Martínez-Castellanos, Gustavo; Shirai, Keiko; Pelayo-Zaldívar, Clara; Pérez-Flores, Laura J; Sepúlveda-Sánchez, José D

    2009-06-01

    The effects of Lactobacillus plantarum alone or in combination with chitosan were evaluated on quality and color retention in rambutan fruits (Nephelium lappaceum) stored at 25 degrees C and 10 degrees C with 75+/-2.5% of relative humidity for 10 and 15 days, respectively. The development of the microorganisms was evidenced by viability analyses and lactic acid production. The application of L. plantarum significantly improved color retention (a* and L*), and reduced weight losses. The lactobacilli, alone or in combination with chitosan, preserved fruit quality characteristics such as firmness, total soluble solids and titratable acidity. The lactobacilli application on rambutan pericarp produced acidification of pericarp and avoided the browning; thereby desiccation was prevented due to biofilm formation.

  1. Financial stress, attitudes toward money, and scores on a Dream Inventory.

    PubMed

    Kroth, Jerry; Mann, Sonia; Cervantes, Carolina; Jaffe, Matthew; Ristic, Vera

    2010-08-01

    During stock market losses in 2009 and high unemployment, ratings on the KJP Dream Inventory were correlated with factors of the Money Attitude Scale and items on the Contemporary Financial Stress Inventory for 71 graduate students in Counseling Psychology and Education. Correlations were significant for Retention on the Money Attitude Scale with Dissociative Avoidance (-.31), Dreams of falling (.26), Risk-taking in dreams (.24), and Dreaming of being chased (.28). Also, ratings for the Money Attitude Scale of Distrust correlated with Discontentedness in dreams (.33) and Dreams of being chased (.26), Repetitive trauma (.33), Nightmares (.30), and Recurring nightmares (.35). Concern about retention in graduate school due to finances correlated with recalled frequencies of nightmares (.27) and dreams of flying (.25).

  2. Fluoride rinse effect on retention of CaF2 formed on enamel/dentine by fluoride application.

    PubMed

    Falcão, Amanda; Masson, Nadia; Leitão, Tarcísio Jorge; Botelho, Juliana Nunes; Ferreira-Nóbilo, Naiara de Paula; Tabchoury, Cínthia Pereira Machado; Tenuta, Livia Maria Andaló; Cury, Jaime Aparecido

    2016-01-01

    Calcium fluoride-like materials ("CaF2") formed on dental surfaces after professional fluoride application are unstable in the oral environment but can be retained longer with a daily NaF mouthrinse. We tested the effect of twice daily 0.05% NaF rinses on the retention of "CaF2" formed on enamel and dentine after applying acidulated phosphate fluoride (APF). "CaF2" formed on enamel/dentine by APF application significantly decreased after exposure to artificial saliva and the 0.05% NaF rinse was ineffective to avoid this reduction. These findings suggest that the combination of APF and 0.05% NaF is not clinically relevant, either for caries or dental hypersensitivity.

  3. Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice.

    PubMed

    Campus, P; Maiolati, M; Orsini, C; Cabib, S

    2016-12-15

    Genetic and stress-related factors interact to foster mental disorders, possibly through dysfunctional learning. In a previous study we reported that a temporary experience of reduced food availability increases forced swim (FS)-induced helplessness tested 14days after a first experience in mice of the standard inbred C57BL/6(B6) strain but reduces it in mice of the genetically unrelated DBA/2J (D2) strain. Because persistence of FS-induced helplessness influences adaptive coping with stress challenge and involve learning processes the present study tested whether the behavioral effects of restricted feeding involved altered consolidation of FS-related learning. First, we demonstrated that restricted feeding does not influence behavior expressed on the first FS experience, supporting a specific effect on persistence rather then development of helplessness. Second, we found that FS-induced c-fos expression in the infralimbic cortex (IL) was selectively enhanced in food-restricted (FR) B6 mice and reduced in FR D2 mice, supporting opposite alterations of consolidation processes involving this brain area. Third, we demonstrated that immediate post-FS inactivation of IL prevents 24h retention of acquired helplessness by continuously free-fed mice of both strains, indicating the requirement of a functioning IL for consolidation of FS-related learning in either mouse strain. Finally, in line with the known role of IL in consolidation of extinction memories, we found that restricted feeding selectively facilitated 24h retention of an acquired extinction in B6 mice whereas impairing it in D2 mice. These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. RGD and polyhistidine tumor homing peptides potentiates the action of human Maspin as an antineoplastic candidate.

    PubMed

    Yin, Runting; Guo, Le; Zhang, Jie; Liu, Guangzhao; Yao, Wenjuan; Zhu, Hongyan; Xu, Xiaole; Zhang, Wei

    2016-07-01

    Maspin, a non-inhibitory member of serine protease family, acts as an effective tumor suppressor by inhibiting cell inhesion and mobility. We found that exogenous wild-type rMaspin had a low effect on tumor growth in vivo. However, when the peptide Arg-Gly-Asp-hexahistidine (RGD-6His) was introduced into rMaspin, the modified rMaspin showed significant inhibitory activity in angiogenic assays and tumor-bearing animal models. Overall, our data suggested that both the RGD and hexahistidine fragments contributed to improve the fusion protein activity and polyhistidine peptide could be considered as flexible linker to separate RGD and Maspin moieties to avoid function interference. Besides, it is an efficient tag to achieve purified recombinant proteins. Furthermore, rMaspin fusing with RGD and hexahistidine could be a viable anticancer candidate.

  5. Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice.

    PubMed

    Vignisse, Julie; Steinbusch, Harry W M; Bolkunov, Alexei; Nunes, Joao; Santos, Ana Isabel; Grandfils, Christian; Bachurin, Sergei; Strekalova, Tatyana

    2011-03-30

    Pre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Role of Dopamine Receptors Subtypes, D1-Like and D2-Like, within the Nucleus Accumbens Subregions, Core and Shell, on Memory Consolidation in the One-Trial Inhibitory Avoidance Task

    ERIC Educational Resources Information Center

    Manago, Francesca; Castellano, Claudio; Oliverio, Alberto; Mele, Andrea; De Leonibus, Elvira

    2009-01-01

    Recent evidence demonstrated that dopamine within the nucleus accumbens mediates consolidation of both associative and nonassociative memories. However, the specific contribution of the nucleus accumbens subregions, core and shell, and of D1 and D2 receptors subtypes has not been yet clarified. The aim of this study was, therefore, to directly…

  7. Antidepressant, psychostimulant, and nootropic effects of major and trace element composition.

    PubMed

    Afanasieva, O G; Suslov, N I; Shilova, I V

    2013-06-01

    The antidepressant, psychostimulant, and nootropic effects of a composition of major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc sulfate were studied on the models of behavioural despair (Porsolt test) and conditioned passive avoidance test. The preparation was found to shorten the immobilization time in the Porsolt test and promote retention of the conditioned passive avoidance. The most pronounced psychostimulant effect of the substance was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the preparation was found at a dose of 93.6 mg/kg.

  8. Avoiding The Inevitable? Capacity Loss From Reservoir Sedimentation

    USGS Publications Warehouse

    Gray, John R.; Randle, Timothy J.; Collins, Kent L.

    2013-01-01

    The inexorable loss of capacity of the nation's reservoirs—sooner or later threatening water supplies for municipal, agricultural, and industrial uses—is but one of a number of deleterious effects wrought by sediment deposition. Trapped sediments can also damage or bury dam outlets, water intakes, and related infrastructure. Downstream effects of sediment capture and retention by reservoirs can include channel and habitat degradation and biotic alterations.

  9. Teacher Retention in Tennessee: Are We Keeping Our Best Teachers? Policy Brief

    ERIC Educational Resources Information Center

    Pratt, Tony; Booker, Laura

    2014-01-01

    While most teachers in Tennessee remain in their positions for many years, it is also the case that some of the most effective teachers depart each year, either to go teach in a different school, a different district, or sometimes to leave the profession entirely. Not all of these moves are avoidable, but finding ways to retain as many high…

  10. Isolation of a small molecule with anti-MRSA activity from a mangrove symbiont Streptomyces sp. PVRK-1 and its biomedical studies in Zebrafish embryos.

    PubMed

    Kannan, Rajaretinam Rajesh; Iniyan, Appadurai Muthamil; Prakash, Vincent Samuel Gnana

    2011-10-01

    The aim of the present study was to isolate the anti-MRSA (Methicillin Resistant Staphylococcus aureus) molecule from the Mangrove symbiont Streptomyces and its biomedical studies in Zebrafish embryos. MRSA was isolated from the pus samples of Colachal hospitals and confirmed by amplification of mecA gene. Anti-MRSA molecule producing strain was identified by 16s rRNA gene sequencing. Anti-MRSA compound production was optimized by Solid State Fermentation (SSF) and the purification of the active molecule was carried out by TLC and RP-HPLC. The inhibitory concentration and LC50 were calculated using Statistical software SPSS. The Biomedical studies including the cardiac assay and organ toxicity assessment were carried out in Zebrafish. The bioactive anti-MRSA small molecule A2 was purified by TLC with Rf value of 0.37 with 1.389 retention time at RP-HPLC. The Inhibitory Concentration of the purified molecule A2 was 30 µg/mL but, the inhibitory concentration of the MRSA in the infected embryo was 32-34 µg/mL for TLC purified molecule A2 with LC50 mean value was 61.504 µg/mL. Zebrafish toxicity was assessed in 48-60 µg/mL by observing the physiological deformities and the heart beat rates (HBR) of embryos for anti MRSA molecule showed the mean of 41.33-41.67 HBR/15 seconds for 40 µg/mL and control was 42.33-42.67 for 15 seconds which significantly showed that the anti-MRSA molecule A2 did not affected the HBR. Anti-MRSA molecule from Streptomyces sp PVRK-1 was isolated and biomedical studies in Zebrafish model assessed that the molecule was non toxic at the minimal inhibitory concentration of MRSA.

  11. Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive Markers of Children’s Sensitivity to Punishment

    PubMed Central

    Gonzalez-Gadea, Maria Luz; Scheres, Anouk; Tobon, Carlos Andres; Damm, Juliane; Baez, Sandra; Huepe, David; Marino, Julian; Marder, Sandra; Manes, Facundo; Abrevaya, Sofia; Ibanez, Agustin

    2015-01-01

    Neurodevelopmental evidence suggests that children’s main decision-making strategy is to avoid options likely to induce punishment. However, the cognitive and affective factors contributing to children’s avoidance to high punishment frequency remain unknown. The present study explored psychophysiological, cognitive, and metacognitive processes associated with sensitivity to punishment frequency. We evaluated 54 participants (between 8 and 15 years old) with a modified Iowa Gambling Task for children (IGT-C) which included options with varying long-term profit and punishment frequencies. Skin conductance responses (SCRs) were recorded during this task. Additionally, we assessed IGT-C metacognitive knowledge, fluid intelligence, and executive functions. Participants exhibited behavioral avoidance and high anticipatory SCRs to options with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge, and inhibitory control were associated with individual differences in sensitivity to punishment frequency. Our results suggest that children’s preference for infrequently punished decisions is partially explained by psychophysiological signals as well as task complexity and development of cognitive control. PMID:26218584

  12. Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive Markers of Children's Sensitivity to Punishment.

    PubMed

    Gonzalez-Gadea, Maria Luz; Scheres, Anouk; Tobon, Carlos Andres; Damm, Juliane; Baez, Sandra; Huepe, David; Marino, Julian; Marder, Sandra; Manes, Facundo; Abrevaya, Sofia; Ibanez, Agustin

    2015-01-01

    Neurodevelopmental evidence suggests that children's main decision-making strategy is to avoid options likely to induce punishment. However, the cognitive and affective factors contributing to children's avoidance to high punishment frequency remain unknown. The present study explored psychophysiological, cognitive, and metacognitive processes associated with sensitivity to punishment frequency. We evaluated 54 participants (between 8 and 15 years old) with a modified Iowa Gambling Task for children (IGT-C) which included options with varying long-term profit and punishment frequencies. Skin conductance responses (SCRs) were recorded during this task. Additionally, we assessed IGT-C metacognitive knowledge, fluid intelligence, and executive functions. Participants exhibited behavioral avoidance and high anticipatory SCRs to options with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge, and inhibitory control were associated with individual differences in sensitivity to punishment frequency. Our results suggest that children's preference for infrequently punished decisions is partially explained by psychophysiological signals as well as task complexity and development of cognitive control.

  13. Identification of Abscisic Acid in Tulipa gesneriana L. by Gas-Liquid Chromatography with Electron Capture and Combined Gas-Liquid Chromatography and Mass Spectrometry

    PubMed Central

    Terry, Paul H.; Aung, Louis H.; De Hertogh, August A.

    1982-01-01

    A major growth inhibitory substance of tulip bulbs (Tulipa gesneriana L. cv Paul Richter) has been unequivocally shown to be abscisic acid (ABA). The ABA methyl ester of the free ether-soluble acid fractions of tulip organs had the identical retention time on gas-liquid chromatography with electron capture detector as authentic ABA methyl ester. In addition, the mass spectra were the same. On a unit dry matter basis, the basalplate and floral shoot contained 3.6 and 2.6 times more ABA than the fleshy scales, respectively. PMID:16662721

  14. Opposing effects of AMPA and 5-HT1A receptor blockade on passive avoidance and object recognition performance: correlation with AMPA receptor subunit expression in rat hippocampus.

    PubMed

    Schiapparelli, L; Simón, A M; Del Río, J; Frechilla, D

    2006-06-01

    It has been suggested that antagonists at serotonin 5-HT1A receptors may exert a procognitive effect by facilitating glutamatergic neurotransmission. Here we further explored this issue by looking for the ability of a 5-HT1A antagonist to prevent the learning deficit induced by AMPA receptor blockade in two behavioural procedures in rats, and for concomitant molecular changes presumably involved in memory formation in the hippocampus. Pretraining administration of the competitive AMPA receptor antagonist, NBQX, produced a dose-related retention impairment in a passive avoidance task 24h later, and also impaired retention in a novel object recognition test when an intertrial interval of 3h was selected. Pretreatment with the selective 5-HT1A receptor antagonist, WAY-100635, prevented the learning deficit induced by NBQX in the two behavioural procedures. In biochemical studies performed on rat hippocampus after the retention tests, we found that learning increased the membrane levels of AMPA receptor GluR1 and GluR2/3 subunits, as well as the phosphorylated forms of GluR1, effects that were abolished by NBQX administration before the training session. Pretreatment with WAY-100635 counteracted the NBQX effects and restored the initial learning-specific increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) function and the later increase in GluR2/3 and phosphorylated GluR1 surface expression. Moreover, administration of WAY-100635 before object recognition training improved recognition memory 24h later and potentiated the learning-associated increase in AMPA receptor subunits. The results support the proposed utility of 5-HT1A antagonists in the treatment of cognitive disorders.

  15. Improving utilization of and retention in PMTCT services: can behavioral economics help?

    PubMed

    Taylor, Nicholas Kenji; Buttenheim, Alison M

    2013-10-10

    The most recent strategic call to action of the World Health Organization sets the elimination of pediatric HIV as a goal. While recent efforts have focused on building infrastructure and ensuring access to high-quality treatment, we must now turn our focus to the behavior change needed to eliminate vertical transmission. We make the case for the application of concepts from the field of behavioral economics to prevention of mother-to-child transmission (PMTCT) programs to more effectively address demand-side issues of uptake and retention. We introduce five concepts from the field of behavioral economics and discuss their application to PMTCT programs: 1) Mentor mothers who come from similar circumstances as PMTCT patients can serve as social references who provide temporally salient modeling of utilization of services and adherence to treatment. 2) Economic incentives, like cell phone minutes or food vouchers, that reward adherence to PMTCT protocols leverage present bias, the observation that people are generally biased toward immediate versus future awards. 3) Default bias, our preference for the default option, is already being used in many countries in the form of opt-out testing, and could be expanded to all PMTCT programs. 4) We are hardwired to avoid loss more than to pursue an equivalent gain. PMTCT programs can take advantage of loss aversion through the use of commitment contracts that incentivize mothers to return to the clinic in order to avoid both reputational and financial loss. Eliminating vertical transmission of HIV is an ambitious goal. To close the remaining gap, innovations are needed to address demand for PMTCT services. Behavioral economics offers a set of tools that can be engineered into PMTCT programs to increase uptake and improve retention with minimal investment.

  16. Evaluation of acute tacrine treatment on passive-avoidance response, open-field behavior, and toxicity in 17- and 30-day-old mice.

    PubMed

    Pan, S Y; Han, Y F; Yu, Z L; Yang, R; Dong, H; Ko, K M

    2006-09-01

    The potential of tacrine in altering cognitive/behavioral function as well as in causing toxicity was evaluated in mice of 17 and 30 days of age. Cognitive and behavioral studies were performed using a step-through passive avoidance task and a habituation open-field test with a 24-h retention interval. Tacrine was subcutaneously injected (1.25-80 micro mol/kg) 30 min prior to the first session of both tests. During the training session in step-through task, tacrine treatment dose-dependently decreased the number of footshocks, with IC(50) values being 7.8 and 23.3 micro mol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 micro mol/kg) significantly prolonged the retention latency in 17-day-old mice only, but it shortened the retention latency at high doses of 20 and 40 micro mol/kg in 17- and 30-day-old, respectively. During the acquisition session in the open-field test, tacrine treatment dose-dependently decreased the locomotor activity in 17- and 30-day-old mice, with IC(50) values being 15.1 and 24.7 micro mol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 micro mol/kg caused a significant increase in serum alanine aminotransferase activity in 17- and 30-day-old mice at 6 h post-dosing, with the extent of stimulation in 30-day-old mice being more prominent. In conclusion, tacrine was more potent in enhancing/disrupting the cognitive function, inhibiting locomotor activity as well as in causing hepatotoxicity in 17-day-old than in 30-day-old mice.

  17. Improving utilization of and retention in PMTCT services: Can behavioral economics help?

    PubMed Central

    2013-01-01

    Background The most recent strategic call to action of the World Health Organization sets the elimination of pediatric HIV as a goal. While recent efforts have focused on building infrastructure and ensuring access to high-quality treatment, we must now turn our focus to the behavior change needed to eliminate vertical transmission. We make the case for the application of concepts from the field of behavioral economics to prevention of mother-to-child transmission (PMTCT) programs to more effectively address demand-side issues of uptake and retention. Discussion We introduce five concepts from the field of behavioral economics and discuss their application to PMTCT programs: 1) Mentor mothers who come from similar circumstances as PMTCT patients can serve as social references who provide temporally salient modeling of utilization of services and adherence to treatment. 2) Economic incentives, like cell phone minutes or food vouchers, that reward adherence to PMTCT protocols leverage present bias, the observation that people are generally biased toward immediate versus future awards. 3) Default bias, our preference for the default option, is already being used in many countries in the form of opt-out testing, and could be expanded to all PMTCT programs. 4) We are hardwired to avoid loss more than to pursue an equivalent gain. PMTCT programs can take advantage of loss aversion through the use of commitment contracts that incentivize mothers to return to the clinic in order to avoid both reputational and financial loss. Summary Eliminating vertical transmission of HIV is an ambitious goal. To close the remaining gap, innovations are needed to address demand for PMTCT services. Behavioral economics offers a set of tools that can be engineered into PMTCT programs to increase uptake and improve retention with minimal investment. PMID:24112440

  18. Minimization of thermal impact by application of electrode cooling in a co-linear PEF treatment chamber.

    PubMed

    Meneses, Nicolas; Jaeger, Henry; Knorr, Dietrich

    2011-10-01

    A co-linear pulsed electric field (PEF) treatment chamber was analyzed and optimized considering electrical process conditions, temperature, and retention of heat-sensitive compounds during a continuous PEF treatment of peach juice. The applicability of a jacket heat-exchanger device surrounding the ground electrode was studied in order to provide active cooling and to avoid temperature peaks within the treatment chamber thus reducing the total thermal load to which the product is exposed. Simulation of the PEF process was performed using a finite element method prior to experimental verification. Inactivation of polyphenoloxydase (PPO) and peroxidase (POD) as well as the degradation of ascorbic acid (AA) in peach juice was quantified and used as indirect indicators for the temperature distribution. Peaks of product temperature within the treatment chamber were reduced, that is, from 98 to 75 °C and retention of the indicators PPO, POD, and AA increased by more than 10% after application of the active electrode cooling device. Practical Application:  The co-linear PEF treatment chamber is widely used for continuous PEF treatment of liquid products and also suitable for industrial scale application; however, Joule heating in combination with nonuniform electric field distribution may lead to unwanted thermal effects. The proposed design showed potential to reduce the thermal load, to which the food is exposed, allowing the retention of heat-sensitive components. The design is applicable at laboratory or industrial scale to perform PEF trials avoiding temperature peaks, which is also the basis for obtaining inactivation kinetic models with minimized thermal impact on the kinetic variables. © 2011 Institute of Food Technologists®

  19. Avoiding Surgical Skill Decay: A Systematic Review on the Spacing of Training Sessions.

    PubMed

    Cecilio-Fernandes, Dario; Cnossen, Fokie; Jaarsma, Debbie A D C; Tio, René A

    Spreading training sessions over time instead of training in just 1 session leads to an improvement of long-term retention for factual knowledge. However, it is not clear whether this would also apply to surgical skills. Thus, we performed a systematic review to find out whether spacing training sessions would also improve long-term retention of surgical skills. We searched the Medline, PsycINFO, Embase, Eric, and Web of Science online databases. We only included articles that were randomized trials with a sample of medical trainees acquiring surgical motor skills in which the spacing effect was reported. The quality and bias of the articles were assessed using the Cochrane Collaboration's risk of bias assessment tool. With respect to the spacing effect, 1955 articles were retrieved. After removing duplicates and articles that did not meet the inclusion criteria, 11 articles remained. The overall quality of the experiments was "moderate." Trainees in the spaced condition scored higher in a retention test than students in the massed condition. Our systematic review showed evidence that spacing training sessions improves long-term surgical skills retention when compared to massed practice. However, the optimal gap between the re-study sessions is unclear. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  20. Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging.

    PubMed

    Steingoetter, A; Kunz, P; Weishaupt, D; Mäder, K; Lengsfeld, H; Thumshirn, M; Boesiger, P; Fried, M; Schwizer, W

    2003-10-01

    Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric-retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research. To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric-retentive floating tablet using magnetic resonance imaging in the sitting position. A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food-filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5-T open-configuration magnetic resonance system. Volunteers were followed over a 4-h period. Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance. Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric-retentive tablets in the human stomach.

  1. RETENTION OF POLYURETHANE FOAM FRAGMENTS DURING VAC-THERAPY, A COMPLICATION TO BE CONSIDERED

    PubMed Central

    Dessy, L.A.; Serratore, F.; Corrias, F.; Parisi, P.; Mazzocchi, M.; Carlesimo, B.

    2013-01-01

    VAC-therapy is a closed-loop, non-invasive active system, characterised by a controlled and localized negative pressure applied on porous polyurethane absorbent foams. It promotes healing of acute and chronic wounds. Therapeutic effects of VAC-therapy have been proved and demonstrated, however this method can have some disadvantages. Even if it is a quite versatile device, only qualified medical/paramedical personnel should use it in order to avoid possible complications that can occur after an improper application. In this report, 11 cases of foam fragment retention within the wound are presented. This rare complication did not promote healing, but further hindered it. On the basis of our experience, it is mandatory to define indications, benefits and limitations of the VAC-therapy. PMID:23590296

  2. Prior Learning of Relevant Nonaversive Information Is a Boundary Condition for Avoidance Memory Reconsolidation in the Rat Hippocampus.

    PubMed

    Radiske, Andressa; Gonzalez, Maria Carolina; Conde-Ocazionez, Sergio A; Feitosa, Anatildes; Köhler, Cristiano A; Bevilaqua, Lia R; Cammarota, Martín

    2017-10-04

    Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for posttraumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant nonaversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta- and gamma-oscillation power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance and suggest that robust nesting of hippocampal theta-gamma rhythms at the time of retrieval is a specific reconsolidation marker. SIGNIFICANCE STATEMENT Posttraumatic stress disorder (PTSD) is characterized by maladaptive avoidance responses to stimuli or behaviors that represent or bear resemblance to some aspect of a traumatic experience. Disruption of reconsolidation, the process by which reactivated memories become susceptible to modifications, is a promising approach for treating PTSD patients. However, much of what is known about fear-motivated avoidance memory reconsolidation derives from studies based on fear conditioning instead of avoidance-learning paradigms. Using a step-down inhibitory avoidance task in rats, we found that the hippocampus is involved in memory reconsolidation only when the animals acquired the avoidance response in an environment that they had previously learned as safe and showed that increased theta- and gamma-oscillation coupling during reactivation is an electrophysiological signature of this process. Copyright © 2017 the authors 0270-6474/17/379675-11$15.00/0.

  3. Amnesia of inhibitory avoidance by scopolamine is overcome by previous open-field exposure

    PubMed Central

    Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge A.

    2014-01-01

    The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two open-field (OF) sessions of 3 min each (habituated), behaved as control animals after a weak though over-threshold training in IA. However, after OF exposure, IA LTM was formed and expressed in spite of an extensive or restricted to the hippocampus MAChR blockade. It was reported that during and after OF exposure and reexposure there was an increase in both hippocampal and cortical ACh release that would contribute to “prime the substrate,” e.g., by lowering the synaptic threshold for plasticity, leading to LTM consolidation. In the frame of the “synaptic tagging and capture” hypothesis, plasticity-related proteins synthesized during/after the previous OF could facilitate synaptic plasticity for IA in the same structure. However, IA anterograde amnesia by hippocampal protein synthesis inhibition with anisomycin was also prevented by two OF exposures, strongly suggesting that there would be alternative interpretations for the role of protein synthesis in memory formation and that another structure could also be involved in this “OF effect.” PMID:25322799

  4. Cognitive deficits in adult rats by lead intoxication are related with regional specific inhibition of cNOS.

    PubMed

    García-Arenas, Guadalupe; Ramírez-Amaya, Victor; Balderas, Israela; Sandoval, Jimena; Escobar, Martha L; Ríos, Camilo; Bermúdez-Rattoni, Federico

    2004-02-04

    It is well known that lead can affect several cognitive abilities in developing animals. In this work, we investigate the effects of different sub-chronic lead doses (0, 65, 125, 250 and 500 ppm of lead acetate in their drinking water for 14 days) in the performance of male adult rats in a water maze, cue maze and inhibitory avoidance tasks. We found that the acquisition of these tasks was not affected by lead, however, the highest dosage of lead (500 ppm) impaired memory consolidation in spatial and inhibitory avoidance tasks, but not in cue maze task while the 250 ppm dose only affected retrieval of spatial memory. Additionally, hippocampal long-term potentiation (LTP) induction in the perforant path after exposing adult rats to different doses of lead was studied. LTP induction was affected in a dose-dependent manner, and treatments of 250 and 500 ppm completely blocked LTP. We investigated the effects of lead intoxication on the activity of constitutive nitric oxide synthase (cNOS) in different brain regions of adult animals. The activity of cNOS was significantly inhibited in the hippocampus and cerebellum but not in the frontal cortex and brain stem, although lead had accumulated in all brain regions. These results suggest that lead intoxication can impair memory in adult animals and this impairment might be related with region-specific effects on cNOS activity.

  5. Seasonal variations of nitrogen and phosphorus retention in an agricultural drainage river in East China.

    PubMed

    Chen, Dingjiang; Lu, Jun; Wang, Hailong; Shen, Yena; Kimberley, Mark O

    2010-02-01

    Riverine retention decreases loads of nitrogen (N) and phosphorus (P) in running water. It is an important process in nutrient cycling in watersheds. However, temporal riverine nutrient retention capacity varies due to changes in hydrological, ecological, and nutrient inputs into the watershed. Quantitative information of seasonal riverine N and P retention is critical for developing strategies to combat diffuse source pollution and eutrophication in riverine and coastal systems. This study examined seasonal variation of riverine total N (TN) and total P (TP) retention in the ChangLe River, an agricultural drainage river in east China. Water quality, hydrological parameters, and hydrophyte coverage were monitored along the ChangLe River monthly during 2004-2006. Nutrient export loads (including chemical fertilizer, livestock, and domestic sources) entering the river from the catchment area were computed using an export coefficient model based on estimated nutrient sources. Riverine TN and TP retention loads (RNRL and RPRL) were estimated using mass balance calculations. Temporal variations in riverine nutrient retention were analyzed statistically. Estimated annual riverine retention loads ranged from 1,538 to 2,127 t year(-1) for RNRL and from 79.4 to 90.4 t year(-1) for RPRL. Monthly retention loads varied from 6.4 to 300.8 t month(-1) for RNRL and from 1.4 to 15.3 t month(-1) for RPRL. Both RNRL and RPRL increased with river flow, water temperature, hydrophyte coverage, monthly sunshine hours, and total TN and TP inputs. Dissolved oxygen concentration and the pH level of the river water decreased with RNRL and RPRL. Riverine nutrient retention ratios (retention as a percentage of total input) were only related to hydrophyte coverage and monthly sunshine hours. Monthly variations in RNRL and RPRL were functions of TN and TP loads. Riverine nutrient retention capacity varied with environmental conditions. Annual RNRL and RPRL accounted for 30.3-48.3% and 52.5-71.2%, respectively, of total input TN and TP loads in the ChangLe River. Monthly riverine retention ratios were 3.5-88.7% for TN and 20.5-92.6% for TP. Hydrophyte growth and coverage on the river bed is the main cause for seasonal variation in riverine nutrient retention capacity. The total input TN and TP loads were the best indicators of RNRL and RPRL, respectively. High riverine nutrient retention capacity during summer due to hydrophytic growth is favorable to the avoidance of algal bloom in both river systems and coastal water in southeast China. Policies should be developed to strictly control nutrient applications on agricultural lands. Strategies for promoting hydrophyte growth in rivers are desirable for water quality management.

  6. The Role of Inhibition in Avoiding Distraction by Salient Stimuli.

    PubMed

    Gaspelin, Nicholas; Luck, Steven J

    2018-01-01

    Researchers have long debated whether salient stimuli can involuntarily 'capture' visual attention. We review here evidence for a recently discovered inhibitory mechanism that may help to resolve this debate. This evidence suggests that salient stimuli naturally attempt to capture attention, but capture can be avoided if the salient stimulus is suppressed before it captures attention. Importantly, the suppression process can be more or less effective as a result of changing task demands or lapses in cognitive control. Converging evidence for the existence of this suppression mechanism comes from multiple sources, including psychophysics, eye-tracking, and event-related potentials (ERPs). We conclude that the evidence for suppression is strong, but future research will need to explore the nature and limits of this mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Accurate prediction of retention in hydrophilic interaction chromatography by back calculation of high pressure liquid chromatography gradient profiles.

    PubMed

    Wang, Nu; Boswell, Paul G

    2017-10-20

    Gradient retention times are difficult to project from the underlying retention factor (k) vs. solvent composition (φ) relationships. A major reason for this difficulty is that gradients produced by HPLC pumps are imperfect - gradient delay, gradient dispersion, and solvent mis-proportioning are all difficult to account for in calculations. However, we recently showed that a gradient "back-calculation" methodology can measure these imperfections and take them into account. In RPLC, when the back-calculation methodology was used, error in projected gradient retention times is as low as could be expected based on repeatability in the k vs. φ relationships. HILIC, however, presents a new challenge: the selectivity of HILIC columns drift strongly over time. Retention is repeatable in short time, but selectivity frequently drifts over the course of weeks. In this study, we set out to understand if the issue of selectivity drift can be avoid by doing our experiments quickly, and if there any other factors that make it difficult to predict gradient retention times from isocratic k vs. φ relationships when gradient imperfections are taken into account with the back-calculation methodology. While in past reports, the accuracy of retention projections was >5%, the back-calculation methodology brought our error down to ∼1%. This result was 6-43 times more accurate than projections made using ideal gradients and 3-5 times more accurate than the same retention projections made using offset gradients (i.e., gradients that only took gradient delay into account). Still, the error remained higher in our HILIC projections than in RPLC. Based on the shape of the back-calculated gradients, we suspect the higher error is a result of prominent gradient distortion caused by strong, preferential water uptake from the mobile phase into the stationary phase during the gradient - a factor our model did not properly take into account. It appears that, at least with the stationary phase we used, column distortion is an important factor to take into account in retention projection in HILIC that is not usually important in RPLC. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Renal effects of felodipine: a review of experimental evidence and clinical data.

    PubMed

    DiBona, G F

    1990-01-01

    The dihydropyridine calcium channel antagonist felodipine has a wide spectrum of effects on the kidney. From a variety of studies in normotensive and hypertensive animals and human subjects, felodipine produces a decrease in renal vascular resistance that, although predominantly dependent on the decrease in mean arterial pressure (MAP), may be associated with an increase in renal blood flow (RBF). The glomerular filtration rate (GFR) is unchanged. In response to acute felodipine administration, the significant diuresis and natriuresis observed is caused by a direct inhibitory effect on net renal tubular sodium and water reabsorption. While the acute natriuretic response to felodipine administration is modulated by compensatory adaptations over the remainder of the 24-h period and during chronic treatment, the negative sodium balance established is sustained over the duration of the treatment. Renal sodium and water retention are not observed and there is little effect on renal potassium handling. As a vasodilator antihypertensive agent, felodipine produces renal vasodilatation (normal or increased but not decreased RBF) without adverse effects on the GFR or renal sodium and water retention.

  9. The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance.

    PubMed

    Borrego, Francisco; Masilamani, Madhan; Marusina, Alina I; Tang, Xiaobin; Coligan, John E

    2006-01-01

    Immune responses must be tightly regulated to avoid hyporesponsiveness on one hand or excessive inflammation and the development of autoimmunity (hyperresponsiveness) on the other hand. This balance is attained through the throttling of activating signals by inhibitory signals that ideally leads to an adequate immune response against an invader without excessive and extended inflammatory signals that promote the development of autoimmunity. The CD94/NKG2 family of receptors is composed of members with activating or inhibitory potential. These receptors are expressed predominantly on NK cells and a subset of CD8+ T cells, and they have been shown to play an important role in regulating responses against infected and tumorigenic cells. In this review, we discuss the current knowledge about this family of receptors, including ligand and receptor interaction, signaling, membrane dynamics, regulation of gene expression and their roles in disease regulation, infections, and cancer, and bone marrow transplantation.

  10. Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

    PubMed

    Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

    2017-11-07

    Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

  11. Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention.

    PubMed

    Schultz-Lampel, D; Jiang, C; Lindström, S; Thüroff, J W

    1998-01-01

    Sacral foramen neuromodulation--initially applied for the treatment of urinary incontinence--has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with alpha-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6-S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2-5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7-10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a "rebound" phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.

  12. Use of Fe/Al drinking water treatment residuals as amendments for enhancing the retention capacity of glyphosate in agricultural soils.

    PubMed

    Zhao, Yuanyuan; Wendling, Laura A; Wang, Changhui; Pei, Yuansheng

    2015-08-01

    Fe/Al drinking water treatment residuals (WTRs), ubiquitous and non-hazardous by-products of drinking water purification, are cost-effective adsorbents for glyphosate. Given that repeated glyphosate applications could significantly decrease glyphosate retention by soils and that the adsorbed glyphosate is potentially mobile, high sorption capacity and stability of glyphosate in agricultural soils are needed to prevent pollution of water by glyphosate. Therefore, we investigated the feasibility of reusing Fe/Al WTR as a soil amendment to enhance the retention capacity of glyphosate in two agricultural soils. The results of batch experiments showed that the Fe/Al WTR amendment significantly enhanced the glyphosate sorption capacity of both soils (p<0.001). Up to 30% of the previously adsorbed glyphosate desorbed from the non-amended soils, and the Fe/Al WTR amendment effectively decreased the proportion of glyphosate desorbed. Fractionation analyses further demonstrated that glyphosate adsorbed to non-amended soils was primarily retained in the readily labile fraction (NaHCO3-glyphosate). The WTR amendment significantly increased the relative proportion of the moderately labile fraction (HCl-glyphosate) and concomitantly reduced that of the NaHCO3-glyphosate, hence reducing the potential for the release of soil-adsorbed glyphosate into the aqueous phase. Furthermore, Fe/Al WTR amendment minimized the inhibitory effect of increasing solution pH on glyphosate sorption by soils and mitigated the effects of increasing solution ionic strength. The present results indicate that Fe/Al WTR is suitable for use as a soil amendment to prevent glyphosate pollution of aquatic ecosystems by enhancing the glyphosate retention capacity in soils. Copyright © 2015. Published by Elsevier B.V.

  13. Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose Tigecycline.

    PubMed

    Vila, Andrea; Pagella, Hugo; Amadio, Claudio; Leiva, Alejandro

    2016-12-01

    Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline. Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30-60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is probably under-dosed for the treatment of implant and biofilm associated infections.

  14. Social anxiety disorders in clinical practice: differentiating social phobia from avoidant personality disorder.

    PubMed

    Lampe, Lisa

    2015-08-01

    To outline the problems around overlap between social phobia (SAD) and avoidant personality disorder (AVPD) and provide guidelines that may assist clinicians to differentiate these conditions. A constellation of symptoms can be identified that may distinguish AVPD from SAD, with key features being a strong and pervasively negative self-concept, a view of rejection as equating to a global evaluation of the individual as being of little worth and a sense of not fitting in socially that dates from early childhood. It is important to identify the presence of AVPD in order to anticipate potential problems with engagement and retention in therapy, to target treatment interventions and optimise outcome. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  15. The Impact of Chemotherapy, Radiation and Epigenetic Modifiers in Cancer Cell Expression of Immune Inhibitory and Stimulatory Molecules and Anti-Tumor Efficacy.

    PubMed

    Chacon, Jessica Ann; Schutsky, Keith; Powell, Daniel J

    2016-11-14

    Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression. While administration of immunomodulatory antibodies that block the interactions between inhibitory receptors on immune cells and their ligands on tumor cells can mediate cancer regression in a subset of treated patients, it is crucial to understand how genomic destabilizers alter the immune system and malignant cells, including which inhibitory molecules, receptors and/or ligands are upregulated in response to genotoxic stress. Knowledge gained in this area will aid in the rational design of trials that combine genomic destabilizers, epigenetic modifiers and immunotherapeutic agents that may be synergized to improve clinical responses and prevent tumor escape from the immune system. Our review article describes the impact genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers have on anti-tumor immunity and the tumor microenvironment. Although genomic destabilizers cause DNA damage on cancer cells, these therapies can also have diverse effects on the immune system, promote immunogenic cell death or survival and alter the cancer cell expression of immune inhibitor molecules.

  16. Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires Large-Scale Perturbation of the Inhibitory Population

    PubMed Central

    Mrsic-Flogel, Thomas D.

    2017-01-01

    Neurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature discrimination. Strong inhibition (Haider et al., 2013) counterbalances excitation, enabling sensory features to be sharpened and represented by sparse codes (Willmore et al., 2011). This balance between excitation and inhibition makes it difficult to assess the strength, or gain, of recurrent excitatory connections within cortical networks, which is key to understanding their operational regime and the computations that they perform. Networks that combine an unstable high-gain excitatory population with stabilizing inhibitory feedback are known as inhibition-stabilized networks (ISNs) (Tsodyks et al., 1997). Theoretical studies using reduced network models predict that ISNs produce paradoxical responses to perturbation, but experimental perturbations failed to find evidence for ISNs in cortex (Atallah et al., 2012). Here, we reexamined this question by investigating how cortical network models consisting of many neurons behave after perturbations and found that results obtained from reduced network models fail to predict responses to perturbations in more realistic networks. Our models predict that a large proportion of the inhibitory network must be perturbed to reliably detect an ISN regime robustly in cortex. We propose that wide-field optogenetic suppression of inhibition under promoters targeting a large fraction of inhibitory neurons may provide a perturbation of sufficient strength to reveal the operating regime of cortex. Our results suggest that detailed computational models of optogenetic perturbations are necessary to interpret the results of experimental paradigms. SIGNIFICANCE STATEMENT Many useful computational mechanisms proposed for cortex require local excitatory recurrence to be very strong, such that local inhibitory feedback is necessary to avoid epileptiform runaway activity (an “inhibition-stabilized network” or “ISN” regime). However, recent experimental results suggest that this regime may not exist in cortex. We simulated activity perturbations in cortical networks of increasing realism and found that, to detect ISN-like properties in cortex, large proportions of the inhibitory population must be perturbed. Current experimental methods for inhibitory perturbation are unlikely to satisfy this requirement, implying that existing experimental observations are inconclusive about the computational regime of cortex. Our results suggest that new experimental designs targeting a majority of inhibitory neurons may be able to resolve this question. PMID:29074575

  17. Active avoidance learning requires prefrontal suppression of amygdala-mediated defensive reactions.

    PubMed

    Moscarello, Justin M; LeDoux, Joseph E

    2013-02-27

    Signaled active avoidance (AA) paradigms train subjects to prevent an aversive outcome by performing a learned behavior during the presentation of a conditioned cue. This complex form of conditioning involves pavlovian and instrumental components, which produce competing behavioral responses that must be reconciled for the subject to successfully avoid an aversive stimulus. In signaled AA paradigm for rat, we tested the hypothesis that the instrumental component of AA training recruits infralimbic prefrontal cortex (ilPFC) to inhibit central amygdala (CeA)-mediated Pavlovian reactions. Pretraining lesions of ilPFC increased conditioned freezing while causing a corresponding decrease in avoidance; lesions of CeA produced opposite effects, reducing freezing and facilitating avoidance behavior. Pharmacological inactivation experiments demonstrated that ilPFC is relevant to both acquisition and expression phases of AA learning. Inactivation experiments also revealed that AA produces an ilPFC-mediated diminution of pavlovian reactions that extends beyond the training context, even when the conditioned stimulus is presented in an environment that does not allow the avoidance response. Finally, injection of a protein synthesis inhibitor into either ilPFC or CeA impaired or facilitated AA, respectively, showing that avoidance training produces two opposing memory traces in these regions. These data support a model in which AA learning recruits ilPFC to inhibit CeA-mediated defense behaviors, leading to a robust suppression of freezing that generalizes across environments. Thus, ilPFC functions as an inhibitory interface, allowing instrumental control over an aversive outcome to attenuate the expression of freezing and other reactions to conditioned threat.

  18. Co-digestion of ruminal content and blood from slaughterhouse industries: influence of solid concentration and ammonium generation.

    PubMed

    López, I; Passeggi, M; Borzacconi, L

    2006-01-01

    At the present time, organic solid wastes from industries and agricultural activities are considered to be promising substrates for biogas production via anaerobic digestion. Moreover solids stabilisation is required before reutilization or disposal. Slaughterhouses are among the most important industries in Uruguay and produce 150,000 tons of ruminal content (RC) and 30,000 tons of blood per year. In order to determine the influence of the solids and blood contents, the ammonia inhibition and the inoculum adaptation co-digestion batch tests were performed. A set of experiences with TS concentration of 2.5%, 5% and 7.5% and different ratios of RC/blood were carried out using an inoculum from an UASB reactor. In all experiences fast blood hydrolisation was observed. A higher methane production was detected in the experiences with higher TS content. However, the fraction of solids degradation was lower in these experiences. A plateau in the biogas production was found. The free ammonia level, which was above the reported inhibitory levels, could explain this behaviour. After the inhibition period the biogas production restarted probably due to the biomass acclimatisation to the ammonia. In order to determine the inoculum adaptation a new experiment was performed. The inoculum used was the sludge coming from the first set of experiences. Based upon batch tests a 3.5 m3 pilot reactor was designed and started up. Ammonia inhibition was avoided by the start-up strategy and in two weeks the biogas production was 3.5 m3/d. The VS stabilisation with a solid retention time of 20 days was of 43%. The pilot reactor working at steady state had a TS concentration of 3-4% with a ratio of RC/blood of 10:1 at the entrance.

  19. Verbal short-term memory as an articulatory system: evidence from an alternative paradigm.

    PubMed

    Cheung, Him; Wooltorton, Lana

    2002-01-01

    In a series of experiments, the role of articulatory rehearsal in verbal [corrected] short-term memory was examined via a shadowing-plus-recall paradigm. In this paradigm, subjects shadowed a word target presented closely after an auditory memory list before they recalled the list. The phonological relationship between the shadowing target and the final item on the memory list was manipulated. Experiments 1 and 2 demonstrated that targets sounding similar to the list-final memory item generally took longer to shadow than unrelated targets. This inhibitory effect of phonological relatedness was more pronounced with tense- than lax-vowel pseudoword recall lists. The interaction between vowel tenseness and phonological relatedness was replicated in Experiment 3 using shorter lists of real words. In Experiment 4, concurrent articulation was applied during list learning to block rehearsal; consequently, neither the phonological relatedness effect nor its interaction with vowel tenseness emerged. Experiments 5 and 6 manipulated the occurrence frequencies and lexicality of the recall items, respectively, instead of vowel tenseness. Unlike vowel tenseness, these non-articulatory memory factors failed to interact with the phonological relatedness effect. Experiment 7 orthogonally manipulated the vowel tenseness and frequencies of the recall items; slowing in shadowing times due to phonological relatedness was modulated by vowel tenseness but not frequency. Taken together, these results suggest that under the present paradigm, the modifying effect of vowel tenseness on the magnitude of slowing in shadowing due to phonological relatedness is indicative of a prominent articulatory component in verbal short-term retention. The shadowing-plus-recall approach avoids confounding overt recall into internal memory processing, which is an inherent problem of the traditional immediate serial recall and span tasks.

  20. Hippocampal microRNA-mRNA regulatory network is affected by physical exercise.

    PubMed

    Fernandes, Jansen; Vieira, Andre Schwambach; Kramer-Soares, Juliana Carlota; Da Silva, Eduardo Alves; Lee, Kil Sun; Lopes-Cendes, Iscia; Arida, Ricardo Mario

    2018-05-08

    It is widely known that physical activity positively affects the overall health and brain function. Recently, microRNAs (miRNAs) have emerged as potential regulators of numerous biological processes within the brain. These molecules modulate gene expression post-transcriptionally by inducing mRNA degradation and inhibiting the translation of target mRNAs. To verify whether the procognitive effects of physical exercise are accompanied by changes in the activity of miRNA-mRNA network in the brain, differential expression analysis was performed in the hippocampus of control (CTL) and exercised (Ex) rats subjected to 4 weeks of treadmill exercise. Cognition was evaluated by a multiple trial inhibitory avoidance (MTIA) task and Illumina next-generation sequencing (NGS) was used for miRNA and mRNA profiling. Exercise improved memory retention but not acquisition in the MTIA task. It was observed that 4 miRNAs and 54 mRNAs were significantly altered in the hippocampus of Ex2 (euthanized 2 h after the last exercise bout) group when compared to CTL group. Bioinformatic analysis showed an inverse correlation between 3 miRNAs and 6 target mRNAs. The miRNAs miR-129-1-3p and miR-144-5p were inversely correlated to the Igfbp5 and Itm2a, respectively, and the miR-708-5p presented an inverse correlation with Cdkn1a, Per2, Rt1-a2. The exercise-induced memory improvements are accompanied by changes in hippocampal miRNA-mRNA regulatory network. Physical exercise can affect brain function through modulation of epigenetics mechanisms involving miRNA regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. The more total cognitive load is reduced by cues, the better retention and transfer of multimedia learning: A meta-analysis and two meta-regression analyses.

    PubMed

    Xie, Heping; Wang, Fuxing; Hao, Yanbin; Chen, Jiaxue; An, Jing; Wang, Yuxin; Liu, Huashan

    2017-01-01

    Cueing facilitates retention and transfer of multimedia learning. From the perspective of cognitive load theory (CLT), cueing has a positive effect on learning outcomes because of the reduction in total cognitive load and avoidance of cognitive overload. However, this has not been systematically evaluated. Moreover, what remains ambiguous is the direct relationship between the cue-related cognitive load and learning outcomes. A meta-analysis and two subsequent meta-regression analyses were conducted to explore these issues. Subjective total cognitive load (SCL) and scores on a retention test and transfer test were selected as dependent variables. Through a systematic literature search, 32 eligible articles encompassing 3,597 participants were included in the SCL-related meta-analysis. Among them, 25 articles containing 2,910 participants were included in the retention-related meta-analysis and the following retention-related meta-regression, while there were 29 articles containing 3,204 participants included in the transfer-related meta-analysis and the transfer-related meta-regression. The meta-analysis revealed a statistically significant cueing effect on subjective ratings of cognitive load (d = -0.11, 95% CI = [-0.19, -0.02], p < 0.05), retention performance (d = 0.27, 95% CI = [0.08, 0.46], p < 0.01), and transfer performance (d = 0.34, 95% CI = [0.12, 0.56], p < 0.01). The subsequent meta-regression analyses showed that dSCL for cueing significantly predicted dretention for cueing (β = -0.70, 95% CI = [-1.02, -0.38], p < 0.001), as well as dtransfer for cueing (β = -0.60, 95% CI = [-0.92, -0.28], p < 0.001). Thus in line with CLT, adding cues in multimedia materials can indeed reduce SCL and promote learning outcomes, and the more SCL is reduced by cues, the better retention and transfer of multimedia learning.

  2. The more total cognitive load is reduced by cues, the better retention and transfer of multimedia learning: A meta-analysis and two meta-regression analyses

    PubMed Central

    Hao, Yanbin; Chen, Jiaxue; An, Jing; Wang, Yuxin; Liu, Huashan

    2017-01-01

    Cueing facilitates retention and transfer of multimedia learning. From the perspective of cognitive load theory (CLT), cueing has a positive effect on learning outcomes because of the reduction in total cognitive load and avoidance of cognitive overload. However, this has not been systematically evaluated. Moreover, what remains ambiguous is the direct relationship between the cue-related cognitive load and learning outcomes. A meta-analysis and two subsequent meta-regression analyses were conducted to explore these issues. Subjective total cognitive load (SCL) and scores on a retention test and transfer test were selected as dependent variables. Through a systematic literature search, 32 eligible articles encompassing 3,597 participants were included in the SCL-related meta-analysis. Among them, 25 articles containing 2,910 participants were included in the retention-related meta-analysis and the following retention-related meta-regression, while there were 29 articles containing 3,204 participants included in the transfer-related meta-analysis and the transfer-related meta-regression. The meta-analysis revealed a statistically significant cueing effect on subjective ratings of cognitive load (d = −0.11, 95% CI = [−0.19, −0.02], p < 0.05), retention performance (d = 0.27, 95% CI = [0.08, 0.46], p < 0.01), and transfer performance (d = 0.34, 95% CI = [0.12, 0.56], p < 0.01). The subsequent meta-regression analyses showed that dSCL for cueing significantly predicted dretention for cueing (β = −0.70, 95% CI = [−1.02, −0.38], p < 0.001), as well as dtransfer for cueing (β = −0.60, 95% CI = [−0.92, −0.28], p < 0.001). Thus in line with CLT, adding cues in multimedia materials can indeed reduce SCL and promote learning outcomes, and the more SCL is reduced by cues, the better retention and transfer of multimedia learning. PMID:28854205

  3. An analytical model to design circumferential clasps for laser-sintered removable partial dentures.

    PubMed

    Alsheghri, Ammar A; Alageel, Omar; Caron, Eric; Ciobanu, Ovidiu; Tamimi, Faleh; Song, Jun

    2018-06-21

    Clasps of removable partial dentures (RPDs) often suffer from plastic deformation and failure by fatigue; a common complication of RPDs. A new technology for processing metal frameworks for dental prostheses based on laser-sintering, which allows for precise fabrication of clasp geometry, has been recently developed. This study sought to propose a novel method for designing circumferential clasps for laser-sintered RPDs to avoid plastic deformation or fatigue failure. An analytical model for designing clasps with semicircular cross-sections was derived based on mechanics. The Euler-Bernoulli elastic curved beam theory and Castigliano's energy method were used to relate the stress and undercut with the clasp length, cross-sectional radius, alloy properties, tooth type, and retention force. Finite element analysis (FEA) was conducted on a case study and the resultant tensile stress and undercut were compared with the analytical model predictions. Pull-out experiments were conducted on laser-sintered cobalt-chromium (Co-Cr) dental prostheses to validate the analytical model results. The proposed circumferential clasp design model yields results in good agreement with FEA and experiments. The results indicate that Co-Cr circumferential clasps in molars that are 13mm long engaging undercuts of 0.25mm should have a cross-section radius of 1.2mm to provide a retention of 10N and to avoid plastic deformation or fatigue failure. However, shorter circumferential clasps such as those in premolars present high stresses and cannot avoid plastic deformation or fatigue failure. Laser-sintered Co-Cr circumferential clasps in molars are safe, whereas they are susceptible to failure in premolars. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

  4. Chronic treatment with the new anticonvulsant drug lacosamide impairs learning and memory processes in rats: A possible role of BDNF/TrkB ligand receptor system.

    PubMed

    Shishmanova-Doseva, Michaela; Peychev, Lyudmil; Koeva, Yvetta; Terzieva, Dora; Georgieva, Katerina; Peychev, Zhivko

    2018-06-01

    Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide - 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30). All rats were subjected to one active and one passive avoidance tests. The BDNF/TrkB immunohistochemical expression in the hippocampus was measured and serum BDNF was determined. The LCM-treated rats made fewer avoidance responses than controls during acquisition training and in the memory retention test. The number of escapes in the LCM 10 and LCM 30 groups decreased throughout the test, while the rats in the LCM 3 group showed fewer escapes only in the memory test in the active avoidance task. In the step-down test, the latency time of the LCM-30 treated rats was reduced as compared with the controls during the learning session and the short- and long-term memory retention tests. Lacosamide induced a dose-dependent reduction of the hippocampal expression of BDNF and its receptor TrkB. We found no significant difference between BDNF serum levels in the test animals and controls. The results of the study suggest that LCM suppresses the learning and memory processes in rats, with the inhibition of hippocampal BDNF/TrkB ligand receptor system being one of the possible mechanisms causing this effect. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing.

    PubMed

    Malina, Abba; Cameron, Christopher J F; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

    2015-12-08

    In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification.

  6. PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

    PubMed Central

    Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

    2015-01-01

    In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

  7. Carryover effects associated with the single-trial passive avoidance learning task in the young chick.

    PubMed

    Crowe, Simon F; Hale, Matthew W

    2002-09-01

    The single-trial passive avoidance task is a useful procedure for examining learning and memory in the young chick. However, it has recently been suggested that discrepant results reported by different laboratories are due to differences in training procedure. The present study investigated a number of parameters surrounding the passive avoidance task, using day-old White Leghorn, Black Australorp cockerels. The results suggested that presentation of a water-dipped bead immediately after the aversive bead significantly altered retention levels. In addition, when the water-dipped bead was presented after the aversive bead, chicks failed to discriminate between beads for a period of 10 min following exposure to the aversant experience. A novel variant of the passive avoidance procedure, involving pretraining with a water-dipped red bead, training with an aversant-coated red bead, and testing with a dry red bead, was evaluated. A measure of avoidance was calculated using all three trials. It is suggested that the use of a single bead, measured both before and after the training experience and using both aversant- and water-trained controls, results in the most concise characterization of memory-related phenomena in the chick which is not contaminated by a carryover effect from the aversive training experience to the nonaversive bead.

  8. Investigation of neuropsychopharmacological effects of a polyherbal formulation on the learning and memory process in rats.

    PubMed

    Shah, Js; Goyal, Rk

    2011-04-01

    To investigate the neuropsychopharmacological effect of a polyherbal formulation (PHF) on the learning and memory processes in rats. PHF contains Withania somnifera (Ashwagandha), Nardostachys jatamansi (Jatamansi), Rauwolfia serpentina (Sarpagandha), Evolvulus alsinoides (Shankhpushpi), Asparagus racemosus (Shatavari), Emblica officinalis (Amalki), Mucuna pruriens (Kauch bij extract), Hyoscyamus niger (Khurasani Ajmo), Mineral resin (Shilajit), Pearl (Mukta Shukhti Pishti), and coral calcium (Praval pishti). Its effect (500 mg / kg, p.o.) on the learning and memory processes was tested. The activity of PHF on memory acquisition and retention was studied using passive avoidance learning and elevated plus maze model (EPM) in rats. The animals treated with PHF showed a significant decrease in transfer latency as compared to the control group in EPM. PHF also produced significant improvement in passive avoidance acquisition and memory retrieval, as compared to the controls and reduced the latency to reach the shock free zone (SFZ) after 24 hours. The PHF produces significant improvement in passive avoidance acquisition and memory retrieval in rats, which needs further investigation.

  9. Extinction and recovery of an avoidance memory impaired by scopolamine.

    PubMed

    Navarro, N M; Krawczyk, M C; Boccia, M M; Blake, M G

    2017-03-15

    Pre-training administration of scopolamine (SCP) resembles situations of cholinergic dysfunction, leading to memory impairment of mice trained in an inhibitory avoidance task. We suggest here that SCP does not impair memory formation, but acquisition is affected in a way that reduces the strength of the stored memory, thus making this memory less able to control behavior when tested. Hence, a memory trace is stored, but is poorly expressed during the test. Although weakly expressed, this memory shows extinction during successive tests, and can be strengthened by using a reminder. Our results indicate that memories stored under cholinergic dysfunction conditions seem absent or lost, but are in fact present and experience common memory processes, such as extinction, and could be even recovered by using appropriate protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Feasibility trial of a film-based educational intervention for increasing boys’ and girls’ intentions to avoid teenage pregnancy: Study protocol☆

    PubMed Central

    Lohan, Maria; Aventin, Áine; Maguire, Lisa; Clarke, Mike; Linden, Mark; McDaid, Lisa

    2014-01-01

    The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers’ intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs. PMID:25284956

  11. Feasibility trial of a film-based educational intervention for increasing boys' and girls' intentions to avoid teenage pregnancy: Study protocol.

    PubMed

    Lohan, Maria; Aventin, Aine; Maguire, Lisa; Clarke, Mike; Linden, Mark; McDaid, Lisa

    2014-01-01

    The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs.

  12. Chronic postnatal ornithine administration to rats provokes learning deficit in the open field task.

    PubMed

    Viegas, Carolina Maso; Busanello, Estela Natacha Brandt; Tonin, Anelise Miotti; Grings, Mateus; Moura, Alana Pimentel; Ritter, Luciana; Zanatta, Angela; Knebel, Lisiane Aurélio; Lobato, Vannessa Araujo; Pettenuzzo, Letícia Ferreira; Vargas, Carmen Regla; Leipnitz, Guilhian; Wajner, Moacir

    2012-12-01

    Hyperornithinemia is the biochemical hallmark of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, an inherited metabolic disease clinically characterized by mental retardation whose pathogenesis is still poorly known. In the present work, we produced a chemical animal model of hyperornithinemia induced by a subcutaneous injection of saline-buffered Orn (2-5 μmol/g body weight) to rats. High brain Orn concentrations were achieved, indicating that Orn is permeable to the blood brain barrier. We then investigated the effect of early chronic postnatal administration of Orn on physical development and on the performance of adult rats in the open field, the Morris water maze and in the step down inhibitory avoidance tasks. Chronic Orn treatment had no effect on the appearance of coat, eye opening or upper incisor eruption, nor on the free-fall righting reflex and on the adult rat performance in the Morris water maze and in the inhibitory avoidance tasks, suggesting that physical development, aversive and spatial localization were not changed by Orn. However, Orn-treated rats did not habituate to the open field apparatus, implying a deficit of learning/memory. Motor activity was the same for Orn- and saline- injected animals. We also verified that Orn subcutaneous injections provoked lipid peroxidation in the brain, as determined by a significant increase of thiobarbituric acid-reactive substances levels. Our results indicate that chronic early postnatal hyperornithinemia may impair the central nervous system, causing minor disabilities which result in specific learning deficiencies.

  13. Stress increases descending inhibition in mouse and human colon.

    PubMed

    Reed, D E; Zhang, Y; Beyak, M J; Lourenssen, S; Blennerhassett, M G; Paterson, W G; Vanner, S J

    2016-04-01

    A relationship between stress and the symptoms of irritable bowel syndrome (IBS) has been well established but the cellular mechanisms are poorly understood. Therefore, we investigated effects of stress and stress hormones on colonic descending inhibition and transit in mouse models and human tissues. Stress was applied using water avoidance stress (WAS) in the animal model or mimicked using stress hormones, adrenaline (5 nM), and corticosterone (1 μM). Intracellular recordings were obtained from colonic circular smooth muscle cells in isolated smooth muscle/myenteric plexus preparations and the inhibitory junction potential (IJP) was elicited by nerve stimulation or balloon distension oral to the site of recording. Water avoidance stress increased the number of fecal pellets compared to control (p < 0.05). WAS also caused a significant increase in IJP amplitude following balloon distension. Stress hormones also increased the IJP amplitude following nerve stimulation and balloon distension (p < 0.05) in control mice but had no effect in colons from stressed mice. No differences were observed with application of ATP between stress and control tissues, suggesting the actions of stress hormones were presynaptic. Stress hormones had a large effect in the nerve stimulated IJP in human colon (increased >50%). Immunohistochemical studies identified alpha and beta adrenergic receptor immunoreactivity on myenteric neurons in human colon. These studies suggest that WAS and stress hormones can signal via myenteric neurons to increase inhibitory neuromuscular transmission. This could lead to greater descending relaxation, decreased transit time, and subsequent diarrhea. © 2016 John Wiley & Sons Ltd.

  14. Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity.

    PubMed

    Santos, Thays B; Céspedes, Isabel C; Viana, Milena B

    2014-07-01

    Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats

    PubMed Central

    Fowler, S.W.; Ramsey, A.K.; Walker, J.M.; Serfozo, P.; Olive, M.F.; Schachtman, T.R.; Simonyi, A.

    2010-01-01

    Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10 mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 hours after training. However, CDPPB (at 3 mg/kg) attenuated the MK-801 (0.2 mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory. PMID:21093598

  16. Rats with ventral hippocampal damage are impaired at various forms of learning including conditioned inhibition, spatial navigation, and discriminative fear conditioning to similar contexts.

    PubMed

    McDonald, Robert J; Balog, R J; Lee, Justin Q; Stuart, Emily E; Carrels, Brianna B; Hong, Nancy S

    2018-10-01

    The ventral hippocampus (vHPC) has been implicated in learning and memory functions that seem to differ from its dorsal counterpart. The goal of this series of experiments was to provide further insight into the functional contributions of the vHPC. Our previous work implicated the vHPC in spatial learning, inhibitory learning, and fear conditioning to context. However, the specific role of vHPC on these different forms of learning are not clear. Accordingly, we assessed the effects of neurotoxic lesions of the ventral hippocampus on retention of a conditioned inhibitory association, early versus late spatial navigation in the water task, and discriminative fear conditioning to context under high ambiguity conditions. The results showed that the vHPC was necessary for the expression of conditioned inhibition, early spatial learning, and discriminative fear conditioning to context when the paired and unpaired contexts have high cue overlap. We argue that this pattern of effects, combined with previous work, suggests a key role for vHPC in the utilization of broad contextual representations for inhibition and discriminative memory in high ambiguity conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. The "phosphorus pyramid": a visual tool for dietary phosphate management in dialysis and CKD patients.

    PubMed

    D'Alessandro, Claudia; Piccoli, Giorgina B; Cupisti, Adamasco

    2015-01-20

    Phosphorus retention plays a pivotal role in the onset of mineral and bone disorders (MBD) in chronic kidney disease (CKD). Phosphorus retention commonly occurs as a result of net intestinal absorption exceeding renal excretion or dialysis removal. The dietary phosphorus load is crucial since the early stages of CKD, throughout the whole course of the disease, up to dialysis-dependent end-stage renal disease.Agreement exits regarding the need for dietary phosphate control, but it is quite challenging in the real-life setting. Effective strategies to control dietary phosphorus intake include restricting phosphorus-rich foods, preferring phosphorus sourced from plant origin, boiling as the preferred cooking procedure and avoiding foods with phosphorus-containing additives. Nutritional education is crucial in this regard.Based on the existing literature, we developed the "phosphorus pyramid", namely a novel, visual, user-friendly tool for the nutritional education of patients and health-care professionals. The pyramid consists of six levels in which foods are arranged on the basis of their phosphorus content, phosphorus to protein ratio and phosphorus bioavailability. Each has a colored edge (from green to red) that corresponds to recommended intake frequency, ranging from "unrestricted" to "avoid as much as possible".The aim of the phosphorus pyramid is to support dietary counseling in order to reduce the phosphorus load, a crucial aspect of integrated CKD-MBD management.

  18. Response inhibition predicts painful task duration and performance in healthy individuals performing a cold pressor task in a motivational context.

    PubMed

    Karsdorp, P A; Geenen, R; Vlaeyen, J W S

    2014-01-01

    Long-term avoidance of painful activities has shown to be dysfunctional in chronic pain. Pain may elicit escape or avoidance responses automatically, particularly when pain-related fear is high. A conflict may arise between opposing short-term escape/avoidance goals to reduce pain and long-term approach goals to receive a reward. An inhibitory control system may resolve this conflict. It was hypothesized that reduced response inhibition would be associated with greater escape/avoidance during pain, particularly among subjects with higher pain-related fear. Response inhibition was measured with the stop-signal task, and pain-related fear with the Fear of Pain Questionnaire. Participants completed a tone-detection task (TDT) in which they could earn money while being exposed to cold pressor pain. Escape/avoidance was operationalized as the hand immersion time during a cold pressor task (CPT) and the performance on the TDT. Poorer response inhibition was associated with shorter CPT immersion duration and with worse TDT performance. Pain after the CPT was associated with pain-related fear, but not with response inhibition. No supportive evidence was found for the hypothesis that the relation between inhibition and escape/avoidance would be most pronounced for those with higher pain-related fear. In contrast, the relation between response inhibition and number of hits on the TDT was most pronounced for those with lower pain-related fear. The findings suggest that individuals with a stronger ability to inhibit responses in a stop-signal task are better able to inhibit escape/avoidance responses elicited by pain, in the service of a conflicting approach goal. © 2013 European Pain Federation - EFIC®

  19. Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

    PubMed Central

    Mazade, Reece E.

    2013-01-01

    Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light. PMID:23926034

  20. The Impact of Chemotherapy, Radiation and Epigenetic Modifiers in Cancer Cell Expression of Immune Inhibitory and Stimulatory Molecules and Anti-Tumor Efficacy

    PubMed Central

    Chacon, Jessica Ann; Schutsky, Keith; Powell, Daniel J.

    2016-01-01

    Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression. While administration of immunomodulatory antibodies that block the interactions between inhibitory receptors on immune cells and their ligands on tumor cells can mediate cancer regression in a subset of treated patients, it is crucial to understand how genomic destabilizers alter the immune system and malignant cells, including which inhibitory molecules, receptors and/or ligands are upregulated in response to genotoxic stress. Knowledge gained in this area will aid in the rational design of trials that combine genomic destabilizers, epigenetic modifiers and immunotherapeutic agents that may be synergized to improve clinical responses and prevent tumor escape from the immune system. Our review article describes the impact genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers have on anti-tumor immunity and the tumor microenvironment. Although genomic destabilizers cause DNA damage on cancer cells, these therapies can also have diverse effects on the immune system, promote immunogenic cell death or survival and alter the cancer cell expression of immune inhibitor molecules. PMID:27854240

  1. Isolation of a small molecule with anti-MRSA activity from a mangrove symbiont Streptomyces sp. PVRK-1 and its biomedical studies in Zebrafish embryos

    PubMed Central

    Kannan, Rajaretinam Rajesh; Iniyan, Appadurai Muthamil; Prakash, Vincent Samuel Gnana

    2011-01-01

    Objective The aim of the present study was to isolate the anti-MRSA (Methicillin Resistant Staphylococcus aureus) molecule from the Mangrove symbiont Streptomyces and its biomedical studies in Zebrafish embryos. Methods MRSA was isolated from the pus samples of Colachal hospitals and confirmed by amplification of mecA gene. Anti-MRSA molecule producing strain was identified by 16s rRNA gene sequencing. Anti-MRSA compound production was optimized by Solid State Fermentation (SSF) and the purification of the active molecule was carried out by TLC and RP-HPLC. The inhibitory concentration and LC50 were calculated using Statistical software SPSS. The Biomedical studies including the cardiac assay and organ toxicity assessment were carried out in Zebrafish. Results The bioactive anti-MRSA small molecule A2 was purified by TLC with Rf value of 0.37 with 1.389 retention time at RP-HPLC. The Inhibitory Concentration of the purified molecule A2 was 30 µg/mL but, the inhibitory concentration of the MRSA in the infected embryo was 32-34 µg/mL for TLC purified molecule A2 with LC50 mean value was 61.504 µg/mL. Zebrafish toxicity was assessed in 48-60 µg/mL by observing the physiological deformities and the heart beat rates (HBR) of embryos for anti MRSA molecule showed the mean of 41.33-41.67 HBR/15 seconds for 40 µg/mL and control was 42.33-42.67 for 15 seconds which significantly showed that the anti-MRSA molecule A2 did not affected the HBR. Conclusions Anti-MRSA molecule from Streptomyces sp PVRK-1 was isolated and biomedical studies in Zebrafish model assessed that the molecule was non toxic at the minimal inhibitory concentration of MRSA. PMID:23569790

  2. Neutral red cytotoxicity assays for assessing in vivo carbon nanotube ecotoxicity in mussels--Comparing microscope and microplate methods.

    PubMed

    Miller, M A; Bankier, C; Al-Shaeri, M A M; Hartl, M G J

    2015-12-30

    The purpose of the present study was to compare two neutral red retention methods, the more established but very labour-intensive microscope method (NRR) against the more recently developed microplate method (NRU). The intention was to explore whether the sample volume throughput could be increased and potential operator bias avoided. Mussels Mytilus sp. were exposed in vivo to 50, 250 and 500 μg L(-1) single (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Using the NRR method, SWCNTs and MWCNTs caused concentration dependent decreases in neutral red retention time. However, a concentration dependent decrease in optical density was not observed using the NRU method. We conclude that the NRU method is not sensitive enough to assess carbon nanotube ecotoxicity in vivo in environmentally relevant media, and recommend using the NRR method. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A robot end effector exchange mechanism for space applications

    NASA Technical Reports Server (NTRS)

    Gorin, Barney F.

    1990-01-01

    Efficient robot operation requires the use of specialized end effectors or tools for tasks. In spacecraft applications, the microgravity environment precludes the use of gravitational forces to retain the tools in holding fixture. As a result of this, a retention mechanism which forms a part of the tool storage container is required. A unique approach to this problem has resulted in the development of an end effector exchange mechanism that meets the requirements for spaceflight applications while avoiding the complexity usually involved. This mechanism uses multiple latching cams both on the manipulator and in the tool storage container, combined with a system of catch rings to provide retention in both locations and the required failure tolerance. Because of the cam configuration the mechanism operates passively, requiring no electrical commands except those needed to move the manipulator into position. Similarly, it inherently provides interlocks to prevent the release of one cam before its opposite number is engaged.

  4. Retention of polyurethane foam fragments during VAC therapy: a complication to be considered.

    PubMed

    Dessy, Luca A; Serratore, Francesco; Corrias, Federico; Parisi, Paola; Mazzocchi, Marco; Carlesimo, Bruno

    2015-04-01

    Vacuum-assisted closure (VAC) therapy is a closed-loop, non-invasive active system, characterised by a controlled and localised negative pressure applied on porous polyurethane absorbent foams. It promotes healing of acute and chronic wounds. Therapeutic effects of VAC therapy have been proved and demonstrated; however, this method can have some disadvantages. Even if it is a quite versatile device, only qualified medical/paramedical personnel should use it in order to avoid possible complications that can occur after an improper application. In this report, 11 cases of foam-fragment retention within the wound are presented. This rare complication did not promote healing, but further hindered it. On the basis of our experience, it is mandatory to define the indications, benefits and limitations of VAC therapy. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  5. A Looping-Based Model for Quenching Repression

    PubMed Central

    Pollak, Yaroslav; Goldberg, Sarah; Amit, Roee

    2017-01-01

    We model the regulatory role of proteins bound to looped DNA using a simulation in which dsDNA is represented as a self-avoiding chain, and proteins as spherical protrusions. We simulate long self-avoiding chains using a sequential importance sampling Monte-Carlo algorithm, and compute the probabilities for chain looping with and without a protrusion. We find that a protrusion near one of the chain’s termini reduces the probability of looping, even for chains much longer than the protrusion–chain-terminus distance. This effect increases with protrusion size, and decreases with protrusion-terminus distance. The reduced probability of looping can be explained via an eclipse-like model, which provides a novel inhibitory mechanism. We test the eclipse model on two possible transcription-factor occupancy states of the D. melanogaster eve 3/7 enhancer, and show that it provides a possible explanation for the experimentally-observed eve stripe 3 and 7 expression patterns. PMID:28085884

  6. Individual Differences in Children's Corepresentation of Self and Other in Joint Action.

    PubMed

    Milward, Sophie J; Kita, Sotaro; Apperly, Ian A

    2017-05-01

    Previous research has shown that children aged 4-5 years, but not 2-3 years, show adult-like interference from a partner when performing a joint task (Milward, Kita, & Apperly, 2014). This raises questions about the cognitive skills involved in the development of such "corepresentation (CR)" of a partner (Sebanz, Knoblich, & Prinz, 2003). Here, individual differences data from one hundred and thirteen 4- to 5-year-olds showed theory of mind (ToM) and inhibitory control (IC) as predictors of ability to avoid CR interference, suggesting that children with better ToM abilities are more likely to succeed in decoupling self and other representations in a joint task, while better IC is likely to help children avoid interference from a partner's response when selecting their own response on the task. © 2016 The Authors. Child Development published by Wiley Periodicals, Inc. on behalf of Society for Research in Child Development.

  7. Hippocampal awake replay in fear memory retrieval

    PubMed Central

    Wu, Chun-Ting; Haggerty, Daniel; Kemere, Caleb; Ji, Daoyun

    2017-01-01

    Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. Here, after rats acquired a fear memory by receiving mild foot-shocks at a shock zone of a track, we analyzed place cells when the animals were placed back to the track and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal’s current positions to the shock zone, but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place cell pattern underlying the inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval. PMID:28218916

  8. Alcohol and behavioral control: cognitive and neural mechanisms.

    PubMed

    Vogel-Sprott, M; Easdon, C; Fillmore, M; Finn, P; Justus, A

    2001-01-01

    This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer/chair was Muriel Vogel-Sprott. The presentations were (1) Alcohol-induced impairment of inhibitory control: Some commonalities with attention deficit hyperactivity disorder, by Mark Fillmore; (2) Neural interactions that underlie response inhibition under alcohol: A functional magnetic resonance imaging investigation, by Craig Easdon; (3) Intentional control of behavior under alcohol, by Muriel Vogel-Sprott; and (4) Working memory and the disinhibiting effects of alcohol on passive avoidance learning, by Alicia Justius and Peter Finn.

  9. Exposure to retrieval cues improves retention performance and induces changes in ACTH and corticosterone release.

    PubMed

    Gisquet-Verrier, Pascale; Botreau, Fanny; Venero, Cesar; Sandi, Carmen

    2004-05-01

    Memory retrieval can be facilitated by pretest exposure to cues associated with the original training. The present series of experiments was aimed at investigating whether the effectiveness of the retrieval cues might be due to their emotional value and thus be associated to a particular pattern of activation of stress systems. Therefore, the effects of exposing rats to different cueing conditions were investigated both on retention performance and on the level of different stress hormones (ACTH, corticosterone and glucose; the latter as an indirect index of adrenergic/sympathetic nervous system activation). Rats trained in a brightness avoidance discrimination task exhibited an enhancement of the retention performance following exposure to the light discriminative stimulus when delivered 1-day after training and not after 21 days, while exposure to contextual cues led to opposite effects on the retention performance, confirming our previous results. Analyses of the level of stress hormones at the time of testing indicated that when the retrieval cues were effective at the behavioral level, cued rats exhibited higher ACTH plasmatic levels than controls, but did not differ in their glucose or corticosterone levels. Further experiments showed that one day after training, both ACTH and corticosterone levels were elevated in light-cued rats if hormone samples were taken 15 min after cueing. These results show that exposure to an effective retrieval cue is accompanied by the activation of the hypothalamus-pituitary-adrenal axis. The possible involvement of the Corticotropin Releasing Factor at the level of the hypothalamus and amygdala (particularly the central nucleus) on the facilitating effect on retention performance following exposure to aversive training-associated cues is discussed. The present results strengthen the notion that emotion can interact with retrieval processes.

  10. Agile patency system eliminates risk of capsule retention in patients with known intestinal strictures who undergo capsule endoscopy.

    PubMed

    Herrerias, Juan M; Leighton, Jonathan A; Costamagna, Guido; Infantolino, Anthony; Eliakim, Rami; Fischer, Doron; Rubin, David T; Manten, Howard D; Scapa, Eitan; Morgan, Douglas R; Bergwerk, Ari J; Koslowsky, Binyamin; Adler, Samuel N

    2008-05-01

    Capsule endoscopy (CE) of the small bowel has become a standard diagnostic tool, but there have been concerns regarding the risk of capsule retention in certain high-risk groups. The Agile patency system, an ingestible and dissolvable capsule with an external scanner, was developed to allow physicians to perform CE with greater confidence that the capsule will be safely excreted in patients at risk for capsule retention. Our purpose was to assess the ability of the device to help physicians identify which patients with known strictures may safely undergo CE. Patients with known strictures ingested the new patency capsule and underwent periodic scanning until it was excreted. The intestinal tract was considered to be sufficiently patent if the capsule was excreted intact or if the capsule was not detected by the scanner at 30 hours after ingestion. If patency was established, then standard CE was performed. International multicenter study. A total of 106 patients with known strictures. Agile patency system. Performance and safety of Agile patency system. A total of 106 patients ingested the patency capsule. Fifty-nine (56%) excreted it intact and subsequently underwent CE. There were no cases of capsule retention. Significant findings on CE were found in 24 (41%). There were 3 severe adverse events. These results suggest that the Agile patency system is a useful tool for physicians to use before CE in patients with strictures to avoid retention. This group of patients may have a high yield of clinically significant findings at CE. This capsule may determine whether patients who have a contraindication to CE may safely undergo CE and obtain useful diagnostic information.

  11. Rewarding brain stimulation reverses the disruptive effect of amygdala damage on emotional learning.

    PubMed

    Kádár, Elisabet; Ramoneda, Marc; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

    2014-11-01

    Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Jinshui; Qiao, Zhenan -An; Mahurin, Shannon Mark

    A soft chemistry synthetic strategy based on a Friedel Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro-mesoporous architecture with well-preserved organic functional groups, which is effective for carbon capture. Furthermore, this soft chemistry synthetic protocol can be further extended to nanotexture other aromatic-based polymers with robust frameworks.

  13. Home care aide retention: building team spirit to avoid employee walkouts.

    PubMed

    Walter, B M

    1996-08-01

    While home care agencies work to increase productivity and decrease costs, it is easy to lose sight of the value of employees. Because home care aides are seldom in the office, their value to the organization may get overlooked. In this article, one home care agency shares ways to build team spirit among the home care aides and empower them to be better employees. The result has been increased productivity, improved morale, and a more stable workforce.

  14. What role can the rural pipeline play in the recruitment and retention of rural allied health professionals?

    PubMed

    Durey, Angela; Haigh, Margaret; Katzenellenbogen, Judith M

    2015-01-01

    People living in rural areas have poorer health than their urban counterparts with higher morbidity and mortality rates and lower life expectancy. Challenges attracting health professionals to work in rural locations in Australia and elsewhere have been well- documented. In response, the idea of a rural pipeline emerged in the medical literature as a career pathway for doctors, conceptualised as a career continuum starting at school and ending in a committed, appropriately trained and supported rural doctor. This article draws on the literature to consider how the concept of a rural pipeline can be used to enhance recruitment and retention of allied health professionals (AHPs) in Australia. The complexity of the issue is taken into account, acknowledging the diverse professional, organisational and social needs within and between AHPs and their different career pathways. With this in mind, the rural pipeline is adapted and extended to focus on AHPs who enter at any stage of their career to work in rural areas. Barriers to recruitment and retention require multifaceted strategies to encourage and support AHPs at various stages along the pipeline to enter, and remain in, rural practice. Findings from the literature identify discrete themes within and between AHPs about factors influencing their rural recruitment and retention choices and include career stage at entry to rural practice, age, gender, social context, professional support, organisational environment and public-private practice mix in service delivery. These findings underscored the development of an extended rural pipeline adapted to specifically target AHPs. This flexible framework of entry to rural practice can be applied at any stage of their career and includes suggestions of strategies to support retention. Evidence from studies of rural AHPs suggests a flexible approach to recruitment and retention is needed that takes into account the complexity of the issue. The extended rural pipeline adapted to AHPs avoids a one-size-fits-all approach. Instead, it offers a more nuanced approach that addresses the diversity within and between professions and reflects the different stages at which AHPs enter rural practice that can inform recruitment and retention strategies that better meet their needs.

  15. Investigation of Neuropsychopharmacological Effects of a Polyherbal Formulation on the Learning and Memory Process in Rats

    PubMed Central

    Shah, JS; Goyal, RK

    2011-01-01

    Objective: To investigate the neuropsychopharmacological effect of a polyherbal formulation (PHF) on the learning and memory processes in rats. Materials and Methods: PHF contains Withania somnifera (Ashwagandha), Nardostachys jatamansi (Jatamansi), Rauwolfia serpentina (Sarpagandha), Evolvulus alsinoides (Shankhpushpi), Asparagus racemosus (Shatavari), Emblica officinalis (Amalki), Mucuna pruriens (Kauch bij extract), Hyoscyamus niger (Khurasani Ajmo), Mineral resin (Shilajit), Pearl (Mukta Shukhti Pishti), and coral calcium (Praval pishti). Its effect (500 mg / kg, p.o.) on the learning and memory processes was tested. The activity of PHF on memory acquisition and retention was studied using passive avoidance learning and elevated plus maze model (EPM) in rats. Results: The animals treated with PHF showed a significant decrease in transfer latency as compared to the control group in EPM. PHF also produced significant improvement in passive avoidance acquisition and memory retrieval, as compared to the controls and reduced the latency to reach the shock free zone (SFZ) after 24 hours. Conclusion: The PHF produces significant improvement in passive avoidance acquisition and memory retrieval in rats, which needs further investigation. PMID:21731356

  16. Brief postnatal exposure to phenobarbital impairs passive-avoidance learning and sensorimotor gating in rats

    PubMed Central

    Gutherz, Samuel B.; Kulick, Catherine V.; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A.

    2014-01-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference to cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition as compared to vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention as compared to matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. PMID:25112558

  17. Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.

    PubMed

    Gutherz, Samuel B; Kulick, Catherine V; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A

    2014-08-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Panic-modulating effects of alprazolam, moclobemide and sumatriptan in the rat elevated T-maze.

    PubMed

    Sant'Ana, Ana Beatriz; Weffort, Luiz Fernando; de Oliveira Sergio, Thatiane; Gomes, Rafael Calsoni; Frias, Alana Tercino; Matthiesen, Melina; Vilela-Costa, Heloisa Helena; Yamashita, Paula Shimene de Melo; Vasconcelos, Alex Teles; de Bortoli, Valquiria; Del-Ben, Cristina Marta; Zangrossi, Helio

    2016-12-15

    The elevated T-maze was developed to test the hypothesis that serotonin plays an opposing role in the regulation of defensive behaviors associated with anxiety and panic. Previous pharmacological exploitation of this test supports the association between inhibitory avoidance acquisition and escape expression with anxiety and fear/panic, respectively. In the present study, we extend the pharmacological validation of this test by investigating the effects of other putative or clinically effective anxiety- and panic-modulating drugs. The results showed that chronic, but not acute injection of the reversible monoamine oxidase-A inhibitor moclobemide (3, 10 and 30mg/kg) inhibited escape expression, indicating a panicolytic-like effect. The same effect was observed after either acute or chronic treatment with alprazolam (1, 2 and 4mg/kg), a high potency benzodiazepine. This drug also impaired inhibitory avoidance acquisition, suggesting an anxiolytic effect. On the other hand, subcutaneous administration of the 5-HT1D/1B receptor agonist sumatriptan (0.1, 0.5 and 2.5μg/kg) facilitated escape performance, indicating a panicogenic-like effect, while treatment with α-para-chlorophenylalanine (p-CPA; 4days i.p injections of 100mg/kg, or a single i.p injection of 300mg/kg), which caused marked 5-HT depletion in the amygdala and striatum, was without effect. Altogether, these results are in full agreement with the clinical effects of these compounds and offer further evidence that the elevated T-maze has broad predictive validity for the effects of anxiety- and panic-modulating drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Sex and the housing: Effects on behavior, cortisol levels and weight in zebrafish.

    PubMed

    Reolon, Gustavo Kellermann; de Melo, Gabriela Madalena; da Rosa, João Gabriel Dos Santos; Barcellos, Leonardo José Gil; Bonan, Carla Denise

    2018-01-15

    Studies with zebrafish use acclimatizing periods of at least one week immediately before the experiments. During this time, animals can be housed in sexually segregated conditions (only females or males in the tank) or in mixed-sex conditions (both sexes in the tank). The influence of sex and housing conditions regarding the presence of one or two sexes is largely unknown in zebrafish. Our aim was to evaluate the influence that sex and housing regarding the sex of animals had in the open tank task, in the inhibitory avoidance memory test, in cortisol levels and weight in zebrafish. Four groups of animals were used: 1) segregated housed females (only females were kept in the tank); 2) segregated housed males (only males were kept in the tank); 3) mixed-sex housed females (only females were analyzed from a tank containing 50% ratio of each sex); 4) mixed-sex housed males (only males were analyzed from a tank containing 50% ratio of each sex). Males showed higher total distance travelled and mean speed when compared to females. In the inhibitory avoidance memory, sexually segregated animals had higher latencies than their mixed-sex counterparts in the 1day test and sexually segregated females presented a memory that persisted longer and was able to be reinstated. Whole-body cortisol levels were higher in mixed-sex animals while weight was lower in these fish. To the best of our knowledge, this is the first time that effects of sex and housing regarding sex were investigated in behavior and physiology of zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Cocaine Drives Aversive Conditioning via Delayed Activation of Dopamine-Responsive Habenular and Midbrain Pathways

    PubMed Central

    Good, Cameron H.; Rowley, Courtney S.; Xu, Sheng-ping; Wang, Huikun; Burnham, Nathan W.; Hoffman, Alexander F.; Lupica, Carl R.; Ikemoto, Satoshi

    2013-01-01

    Many strong rewards, including abused drugs, also produce aversive effects that are poorly understood. For example, cocaine can produce aversive conditioning after its rewarding effects have dissipated, consistent with opponent process theory, but the neural mechanisms involved are not well known. Using electrophysiological recordings in awake rats, we found that some neurons in the lateral habenula (LHb), where activation produces aversive conditioning, exhibited biphasic responses to single doses of intravenous cocaine, with an initial inhibition followed by delayed excitation paralleling cocaine's shift from rewarding to aversive. Recordings in LHb slice preparations revealed similar cocaine-induced biphasic responses and further demonstrated that biphasic responses were mimicked by dopamine, that the inhibitory phase depended on dopamine D2-like receptors, and that the delayed excitation persisted after drug washout for prolonged durations consistent with findings in vivo. c-Fos experiments further showed that cocaine-activated LHb neurons preferentially projected to and activated neurons in the rostromedial tegmental nucleus (RMTg), a recently identified target of LHb axons that is activated by negative motivational stimuli and inhibits dopamine neurons. Finally, pharmacological excitation of the RMTg produced conditioned place aversion, whereas cocaine-induced avoidance behaviors in a runway operant paradigm were abolished by lesions of LHb efferents, lesions of the RMTg, or by optogenetic inactivation of the RMTg selectively during the period when LHb neurons are activated by cocaine. Together, these results indicate that LHb/RMTg pathways contribute critically to cocaine-induced avoidance behaviors, while also participating in reciprocally inhibitory interactions with dopamine neurons. PMID:23616555

  1. Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

    PubMed

    Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

    2011-01-01

    Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

  2. The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

    PubMed

    Nasehi, Mohammad; Hasanvand, Simin; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

    2018-05-16

    In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25 µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25 µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4 µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625 µg/mouse) or sulpiride (0.1 µg/mouse) increased pre-training harmane (4 and 8 mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625 µg/mouse) reversed amnesia induced by an effective dose of harmane (12 mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625 µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

  3. Morvan's syndrome and the sustained absence of all sleep rhythms for months or years: An hypothesis.

    PubMed

    Touzet, Claude

    2016-09-01

    Despite the predation costs, sleep is ubiquitous in the animal realm. Humans spend a third of their life sleeping, and the quality of sleep has been related to co-morbidity, Alzheimer disease, etc. Excessive wakefulness induces rapid changes in cognitive performances, and it is claimed that one could die of sleep deprivation as quickly as by absence of water. In this context, the fact that a few people are able to go without sleep for months, even years, without displaying any cognitive troubles requires explanations. Theories ascribing sleep to memory consolidation are unable to explain such observations. It is not the case of the theory of sleep as the hebbian reinforcement of the inhibitory synapses (ToS-HRIS). Hebbian learning (Long Term Depression - LTD) guarantees that an efficient inhibitory synapse will lose its efficiency just because it is efficient at avoiding the activation of the post-synaptic neuron. This erosion of the inhibition is replenished by hebbian learning (Long Term Potentiation - LTP) when pre and post-synaptic neurons are active together - which is exactly what happens with the travelling depolarization waves of the slow-wave sleep (SWS). The best documented cases of months-long insomnia are reports of patients with Morvan's syndrome. This syndrome has an autoimmune cause that impedes - among many things - the potassium channels of the post-synaptic neurons, increasing LTP and decreasing LTD. We hypothesize that the absence of inhibitory efficiency erosion during wakefulness (thanks to a decrease of inhibitory LTD) is the cause for an absence of slow-wave sleep (SWS), which results also in the absence of REM sleep. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Social stress alters inhibitory synaptic input to distinct subpopulations of raphe serotonin neurons.

    PubMed

    Crawford, LaTasha K; Rahman, Shumaia F; Beck, Sheryl G

    2013-01-16

    Anxiety disorders are among the most prevalent psychiatric disorders, yet much is unknown about the underlying mechanisms. The dorsal raphe (DR) is at the crux of the anxiety-inducing effects of uncontrollable stress, a key component of models of anxiety. Though DR serotonin (5-HT) neurons play a prominent role, anxiety-associated changes in the physiology of 5-HT neurons remain poorly understood. A 5-day social defeat model of anxiety produced a multifaceted, anxious phenotype in intruder mice that included increased avoidance behavior in the open field test, increased stress-evoked grooming, and increased bladder and heart weights when compared to control mice. Intruders were further compared to controls using electrophysiology recordings conducted in midbrain slices wherein recordings targeted 5-HT neurons of the ventromedial (vmDR) and lateral wing (lwDR) subfields of the DR. Though defining membrane characteristics of 5-HT neurons were unchanged, γ-aminobutyric-acid-mediated (GABAergic) synaptic regulation of 5-HT neurons was altered in a topographically specific way. In the vmDR of intruders, there was a decrease in the frequency and amplitude of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). However, in the lwDR, there was an increase in the strength of inhibitory signals due to slower sIPSC kinetics. Synaptic changes were selective for GABAergic input, as glutamatergic synaptic input was unchanged in intruders. The distinct inhibitory regulation of DR subfields provides a mechanism for increased 5-HT output in vmDR target regions and decreased 5-HT output in lwDR target regions, divergent responses to uncontrollable stress that have been reported in the literature but were previously poorly understood.

  5. The effect of combined avoidance and control training on implicit food evaluation and choice.

    PubMed

    Kakoschke, Naomi; Kemps, Eva; Tiggemann, Marika

    2017-06-01

    Continual exposure to food cues in the environment contributes to unhealthy eating behaviour. According to dual-process models, such behaviour is partly determined by automatic processing of unhealthy food cues (e.g., approach bias), which fails to be regulated by controlled processing (e.g., inhibitory control). The current study aimed to investigate the effect of combined avoidance and control training on implicit evaluation (liking), choice, and consumption of unhealthy snack food. Participants were 240 undergraduate women who were randomly allocated to one of four experimental conditions of a 2 (avoidance training: training versus control) x 2 (control training: training versus control) between-subjects design. The combined training group had a more negative implicit evaluation of unhealthy food than either of the two training conditions alone or the control condition. In addition, participants trained to avoid unhealthy food cues subsequently made fewer unhealthy snack food choices. No significant group differences were found for food intake. Participants were women generally of a healthy weight. Overweight or obese individuals may derive greater benefit from combined training. Results lend support to the theoretical predictions of dual-process models, as the combined training reduced implicit liking of unhealthy food. At a practical level, the findings have implications for the effectiveness of interventions targeting unhealthy eating behaviour. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Effect of EDTA and Fe-EDTA complex concentration on TCF Kraft mill effluent degradability. Batch and continuous treatments.

    PubMed

    Diez, M C; Pouleurs, D; Navia, R; Vidal, G

    2005-09-01

    The effect of ethylenediaminetetracetic acid (EDTA) and Fe-EDTA complex on synthetic totally chlorine-free (TCF) effluent degradability in batch and continuously operating reactors was evaluated. Under batch treatment, the addition of EDTA and Fe-EDTA complex was studied in the range of 80 to 320 mg l(-1). Under continuously operated reactors, the Fe-EDTA complex concentration varied from 20 to 80 mg l(-1), and the hydraulic retention time (HRT) varied from 48 to 24 h. Sludge oxygen uptake rate (OUR) and chemical oxygen demand (COD) removal decreased when EDTA concentration increased in the influent under batch treatment; however, this inhibitory effect was reduced by the addition of Fe-EDTA complex. Without the addition of EDTA, COD removal decreased from 71% to 8%. The most efficient EDTA removal treatment (almost 10%) was the treatment of 80 mg l(-1) Fe-EDTA. Under continuously operated reactors, COD removal was greater than 57% in the synthetic TCF effluent with a Fe-EDTA concentration that varied from 20 to 80 mg l(-1); however, EDTA removal was lower than 25% in all cases. Synthetic TCF effluent with a Fe -EDTA concentration higher than 80 mg l(-1) could not be treated by the activated sludge treatment due to EDTA's inhibitory effect on the sludge.

  7. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.

    PubMed

    von Hundelshausen, Philipp; Agten, Stijn M; Eckardt, Veit; Blanchet, Xavier; Schmitt, Martin M; Ippel, Hans; Neideck, Carlos; Bidzhekov, Kiril; Leberzammer, Julian; Wichapong, Kanin; Faussner, Alexander; Drechsler, Maik; Grommes, Jochen; van Geffen, Johanna P; Li, He; Ortega-Gomez, Almudena; Megens, Remco T A; Naumann, Ronald; Dijkgraaf, Ingrid; Nicolaes, Gerry A F; Döring, Yvonne; Soehnlein, Oliver; Lutgens, Esther; Heemskerk, Johan W M; Koenen, Rory R; Mayo, Kevin H; Hackeng, Tilman M; Weber, Christian

    2017-04-05

    Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting. Copyright © 2017, American Association for the Advancement of Science.

  8. GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain.

    PubMed

    Huang, Hung-Hsiang; Hassinen, Antti; Sundaram, Subha; Spiess, Andrej-Nikolai; Kellokumpu, Sakari; Stanley, Pamela

    2015-09-15

    Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP-L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis.

  9. Comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatography for screening anti-tumor components from Radix Sophorae flavescentis.

    PubMed

    Wang, Qiang; Xu, Junnan; Li, Xiang; Zhang, Dawei; Han, Yong; Zhang, Xu

    2017-07-01

    Radix Sophorae flavescentis is generally used for the treatment of different stages of prostate cancer in China. It has ideal effects when combined with surgical treatment and chemotherapy. However, its active components are still ambiguous. We devised a comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatography system for screening anti-prostate cancer components in Radix Sophorae flavescentis. Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validation and optimization the selectivity and suitability of the comprehensive two-dimensional chromatographic system. Five compounds, sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol were found to have significant retention behaviors on the PC-3 cell membrane chromatography and were unambiguously identified by time-of-flight mass spectrometry. Cell proliferation and apoptosis assays confirmed that all five compounds had anti-prostate cancer effects. Matrine and xanthohumol had good inhibitory effects, with half maximal inhibitory concentration values of 0.893 and 0.137 mg/mL, respectively. Our comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatographic system promotes the efficient recognition and rapid analysis of drug candidates, and it will be practical for the discovery of prostate cancer drugs from complex traditional Chinese medicines. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Thermophilic two-stage dry anaerobic digestion of model garbage with ammonia stripping.

    PubMed

    Yabu, Hironori; Sakai, Chikako; Fujiwara, Tomoko; Nishio, Naomichi; Nakashimada, Yutaka

    2011-03-01

    To avoid the inhibition of methane production by ammonia that occurs during the degradation of garbage, anaerobic digestion with prior ammonia production and subsequent stripping was investigated. In the ammonia production phase, the maximum ammonia concentration was approximately 2800 mg N/kg of total wet sludge in the range of 4 days of sludge retention time, indicating that only 43% of total nitrogen in the model garbage was converted to ammonia. The model garbage from which ammonia was produced and stripped was subjected to semi-continuous thermophilic dry anaerobic digestion over 180 days. The gas yield was in the range of 0.68 to 0.75 Nm(3)/kg volatile solid, and it decreased with the decrease of the sludge retention time. The ammonia-nitrogen concentration in the sludge was kept below 3000 mg N/kg total wet sludge. Microbial community structure analysis revealed that the phylum Firmicutes dominated in the ammonia production, but the community structure changed at different sludge retention times. In dry anaerobic digestion, the dominant bacteria shifted from the phylum Thermotogae to Firmicutes. The dominant archaeon was the genus Methanothermobacter, but the ratio of Methanosarcina increased during the process of dry anaerobic digestion. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  11. Robust algorithm for aligning two-dimensional chromatograms.

    PubMed

    Gros, Jonas; Nabi, Deedar; Dimitriou-Christidis, Petros; Rutler, Rebecca; Arey, J Samuel

    2012-11-06

    Comprehensive two-dimensional gas chromatography (GC × GC) chromatograms typically exhibit run-to-run retention time variability. Chromatogram alignment is often a desirable step prior to further analysis of the data, for example, in studies of environmental forensics or weathering of complex mixtures. We present a new algorithm for aligning whole GC × GC chromatograms. This technique is based on alignment points that have locations indicated by the user both in a target chromatogram and in a reference chromatogram. We applied the algorithm to two sets of samples. First, we aligned the chromatograms of twelve compositionally distinct oil spill samples, all analyzed using the same instrument parameters. Second, we applied the algorithm to two compositionally distinct wastewater extracts analyzed using two different instrument temperature programs, thus involving larger retention time shifts than the first sample set. For both sample sets, the new algorithm performed favorably compared to two other available alignment algorithms: that of Pierce, K. M.; Wood, Lianna F.; Wright, B. W.; Synovec, R. E. Anal. Chem.2005, 77, 7735-7743 and 2-D COW from Zhang, D.; Huang, X.; Regnier, F. E.; Zhang, M. Anal. Chem.2008, 80, 2664-2671. The new algorithm achieves the best matches of retention times for test analytes, avoids some artifacts which result from the other alignment algorithms, and incurs the least modification of quantitative signal information.

  12. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen.

    PubMed

    Safeukui, Innocent; Correas, Jean-Michel; Brousse, Valentine; Hirt, Déborah; Deplaine, Guillaume; Mulé, Sébastien; Lesurtel, Mickael; Goasguen, Nicolas; Sauvanet, Alain; Couvelard, Anne; Kerneis, Sophie; Khun, Huot; Vigan-Womas, Inès; Ottone, Catherine; Molina, Thierry Jo; Tréluyer, Jean-Marc; Mercereau-Puijalon, Odile; Milon, Geneviève; David, Peter H; Buffet, Pierre A

    2008-09-15

    The current paradigm in Plasmodium falciparum malaria pathogenesis states that young, ring-infected erythrocytes (rings) circulate in peripheral blood and that mature stages are sequestered in the vasculature, avoiding clearance by the spleen. Through ex vivo perfusion of human spleens, we examined the interaction of this unique blood-filtering organ with P falciparum-infected erythrocytes. As predicted, mature stages were retained. However, more than 50% of rings were also retained and accumulated upstream from endothelial sinus wall slits of the open, slow red pulp microcirculation. Ten percent of rings were retained at each spleen passage, a rate matching the proportion of blood flowing through the slow circulatory compartment established in parallel using spleen contrast-enhanced ultrasonography in healthy volunteers. Rings displayed a mildly but significantly reduced elongation index, consistent with a retention process, due to their altered mechanical properties. This raises the new paradigm of a heterogeneous ring population, the less deformable subset being retained in the spleen, thereby reducing the parasite biomass that will sequester in vital organs, influencing the risk of severe complications, such as cerebral malaria or severe anemia. Cryptic ring retention uncovers a new role for the spleen in the control of parasite density, opening novel intervention opportunities.

  13. Cellulase retention and sugar removal by membrane ultrafiltration during lignocellulosic biomass hydrolysis.

    PubMed

    Knutsen, Jeffrey S; Davis, Robert H

    2004-01-01

    Technologies suitable for the separation and reuse of cellulase enzymes during the enzymatic saccharification of pretreated corn stover are investigated to examine the economic and technical viability of processes that promote cellulase reuse while removing inhibitory reaction products such as glucose and cellobiose. The simplest and most suitable separation is a filter with relatively large pores on the order of 20-25 mm that retains residual corn stover solids while passing reaction products such as glucose and cellobiose to form a sugar stream for a variety of end uses. Such a simple separation is effective because cellulase remains bound to the residual solids. Ultrafiltration using 50-kDa polyethersulfone membranes to recover cellulase enzymes in solution was shown not to enhance further the saccharification rate or overall conversion. Instead, it appears that the necessary cellulase enzymes, including beta-glucosidase, are tightly bound to the substrate; when fresh corn stover is contacted with highly washed residual solids, without the addition of fresh enzymes, glucose is generated at a high rate. When filtration was applied multiple times, the concentration of inhibitory reaction products such as glucose and cellobiose was reduced from 70 to 10 g/L. However, an enhanced saccharification performance was not observed, most likely because the concentration of the inhibitory products remained too high. Further reduction in the product concentration was not investigated, because it would make the reaction unnecessarily complex and result in a product stream that is much too dilute to be useful. Finally, an economic analysis shows that reuse of cellulase can reduce glucose production costs, especially when the enzyme price is high. The most economic performance is shown to occur when the cellulase enzyme is reused and a small amount of fresh enzyme is added after each separation step to replace lost or deactivated enzyme.

  14. The ventral hippocampus, but not the dorsal hippocampus is critical for learned approach-avoidance decision making.

    PubMed

    Schumacher, Anett; Vlassov, Ekaterina; Ito, Rutsuko

    2016-04-01

    The resolution of an approach-avoidance conflict induced by ambivalent information involves the appraisal of the incentive value of the outcomes and associated stimuli to orchestrate an appropriate behavioral response. Much research has been directed at delineating the neural circuitry underlying approach motivation and avoidance motivation separately. Very little research, however, has examined the neural substrates engaged at the point of decision making when opposing incentive motivations are experienced simultaneously. We hereby examine the role of the dorsal and ventral hippocampus (HPC) in a novel approach-avoidance decision making paradigm, revisiting a once popular theory of HPC function, which posited the HPC to be the driving force of a behavioral inhibition system that is activated in situations of imminent threat. Rats received pre-training excitotoxic lesions of the dorsal or ventral HPC, and were trained to associate different non-spatial cues with appetitive, aversive and neutral outcomes in three separate arms of the radial maze. On the final day of testing, a state of approach-avoidance conflict was induced by simultaneously presenting two cues of opposite valences, and comparing the time the rats spent interacting with the superimposed 'conflict' cue, and the neutral cue. The ventral HPC-lesioned group showed significant preference for the conflict cue over the neutral cue, compared to the dorsal HPC-lesioned, and control groups. Thus, we provide evidence that the ventral, but not dorsal HPC, is a crucial component of the neural circuitry concerned with exerting inhibitory control over approach tendencies under circumstances in which motivational conflict is experienced. © 2015 Wiley Periodicals, Inc.

  15. Use, misuse and abuse of diuretics.

    PubMed

    Bartoli, Ettore; Rossi, Luca; Sola, Daniele; Castello, Luigi; Sainaghi, Pier Paolo; Smirne, Carlo

    2017-04-01

    Resolution of edema requires a correct interpretation of body fluids-related renal function, to excrete the excess volume while restoring systemic hemodynamics and avoiding renal failure. In heart failure, the intensive diuresis should be matched by continuous fluids refeeding from interstitium to plasma, avoiding central volume depletion. The slowly reabsorbed ascites cannot refeed this contracted volume in cirrhosis: the ensuing activation of intrathoracic receptors, attended by increased adrenergic and Renin release, causes more avid sodium retention, producing a positive fluid and Na balance in the face of continuous treatment. High-dose-furosemide creates a defect in tubular Na causing diuresis adequate to excrete the daily water and electrolyte load in Chronic Renal Failure. Diuretic treatment requires care, caution and bedside "tricks" aimed at minimizing volume contraction by correctly assessing the homeostatic system of body fluids and related renal hemodynamics. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. New element for optimizing the functioning of sediment traps

    NASA Astrophysics Data System (ADS)

    Schwindt, Sebastian; Franca, Mário; Schleiss, Anton

    2017-04-01

    Sediment traps protect urban areas against excessive sediment transport during hazardous floods and consist typically of a retention basin with an open sediment check dam at the downstream end. The design, as well as the morphological processes within the retention basin, were analyzed by several authors. With regard to open sediment check dams two types of triggering mechanisms for the initiation of sediment retention can be distinguished: (1) mechanical and (2) hydraulic clogging of the structure. Recent studies have shown that outlet structures combining both clogging principles may be considered to avoid undesired self-flushing. Further elements of check dams are conceivable, e.g. for retaining or conveying driftwood. This study analyses experimentally working principles and design criteria of standard elements of sediment traps. Furthermore, it introduces a new structural element to the sediment trap design with a guiding channel in the retention reservoir. Taking into account the natural shape of mountain rivers, the guiding channel has a trapezoidal cross-section shape and a rough but fixed bed. The effect of the guiding channel on sediment deposition pattern and re-mobilization are studied by means of physical model experiments with a standardized hydrograph and variable sediment supply. The results are evaluated by means of zenithal pictures and bedload transport rate, measured at the downstream end of the model. Major advantages of the combined use of both clogging principles include an improved control of the initiation of sediment deposition in order to allow for sediment transfer for small floods and a reduction of hazards related to self-flushing.

  17. A Qualitative Study on Patients' Perceptions of Two Types of Attachments for Implant Overdentures.

    PubMed

    Pisani, Marina; Bedos, Christophe; da Silva, Cláudia Helena Lovato; Fromentin, Olivier; de Albuquerque, Rubens F

    2017-12-01

    The aim of this qualitative study was to gain a deeper understanding of patient perceptions of wearing implant-retained overdentures with ball-shaped or cylindrical attachment systems. Twenty-two wearers of implant-supported overdentures participated in this qualitative study based on a randomized crossover clinical trial that aimed to compare a cylindrical attachment and a ball attachment. In phase I of the study, group A experienced ball attachments (n = 11) and group B Locator attachments (n = 11) for 1 year. Afterward, in phase II, the attachments were changed; group A received Locator attachments and group B received ball attachments. One week after the attachment's replacement, semistructured individual interviews were conducted. All interviews were audiotaped and transcribed. The analysis was guided by thematic content analysis. Most of the patients from both groups preferred the attachment they received in phase II, regardless the type. A major theme raised by the participants to justify their preference between the attachment types was prosthesis retention/stability, sometimes considered as a positive and other times as a negative factor. Other themes were also explored: oral function, pain, hygiene, previous experiences, confidence on the dentist's work, and esthetic. Aspects related to the retention/stability of the overdentures are the main concerns associated with the perceptions of most patients treated with implant overdentures regardless of the type of attachment. Adequate retention level should be identified and adjusted on an individual basis and maintained overtime as possible. Therefore, follow-up appointments should be planned for readjustment of the attachment's retention. Overretention should be avoided.

  18. Severe hypertriglyceridemia in Puerto Rico blood donors: a population study 2009-2011.

    PubMed

    Morales-Borges, Raúl H; Merced, Carmen

    2012-01-01

    Puerto Rico blood donor issues has been identified in cases of severe hypertriglyceridemia presenting as turbid. Blood donations resulting in milky serum must be discarded. They are discarded because we cannot properly test the donation. This is the first report where we correlate turbidity and cardiovascular risk factors in the Puerto Rico population as well as blood types O and A, Rh (+) with dyslipidemia. Blood donors should be screened in more details regarding cardiovascular and metabolic risks to avoid problems with recruitment and retention strategies.

  19. 2017 European guidelines for the management of genital herpes.

    PubMed

    Patel, Rajul; Kennedy, Oliver J; Clarke, Emily; Geretti, Anna; Nilsen, Arvid; Lautenschlager, Stephan; Green, John; Donders, Gilbert; van der Meijden, Willem; Gomberg, Mikhail; Moi, Harald; Foley, Elizabeth

    2017-12-01

    Genital herpes is one of the commonest sexually transmitted infections worldwide. Using the best available evidence, this guideline recommends strategies for diagnosis, management, and follow-up of the condition as well as for minimising transmission. Early recognition and initiation of therapy is key and may reduce the duration of illness or avoid hospitalisation with complications, including urinary retention, meningism, or severe systemic illness. The guideline covers a range of common clinical scenarios, such as recurrent genital herpes, infection during pregnancy, and co-infection with human immunodeficiency virus.

  20. Hypercrosslinked phenolic polymers with well developed mesoporous frameworks

    DOE PAGES

    Zhang, Jinshui; Qiao, Zhenan -An; Mahurin, Shannon Mark; ...

    2015-02-12

    A soft chemistry synthetic strategy based on a Friedel Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro-mesoporous architecture with well-preserved organic functional groups, which is effective for carbon capture. Furthermore, this soft chemistry synthetic protocol can be further extended to nanotexture other aromatic-based polymers with robust frameworks.

  1. Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

    PubMed Central

    Brogden, Nicole K.; Brogden, Kim A.

    2011-01-01

    The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent promising therapeutic agents against bacterial and fungal agents. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or ‘targeted’ antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo. PMID:21733662

  2. Emulsification and antioxidation of biosurfactant extracts from Chinese medicinal herbs fermentation in vitro.

    PubMed

    Chen, Chunyeh; Lin, Tachen; Shieh, Youmin

    2015-10-01

    Much attention has been paid to biosurfactants produced using microorganisms, but little direct evidence for the development of natural biosurfactants combined with Chinese medicinal herbs are available. We investigated the emulsification and antioxidation of biosurfactant extracts from Chinese medicinal herb fermentation (BECMHF) in vitro and their application in water retention capacity and the skin prick and allergy test (SPAT) index for skin cells. The results showed that the water retention capacity of BECMHF was positively associated with the emulsification index. The SPAT index of 8 Chinese medicinal herbs was 0 at a 1% or 2% concentration, suggesting no sensitivity or adverse effects on the skin cells. Eight BECMHFs produced using Alcaligenes piechaudii CC-ESB2 exhibited antioxidant capabilities, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide scavenging activity, and superoxide dismutase (SOD)-like activity at a concentration of 10 mg/ml. The mechanism involved inhibitory effects on nitrite, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species (ROSs) generation. BECMHFs exhibit favorable antioxidative properties in health food and satisfactory emulsifying and moisturizing characteristics in cosmetic formulations, which have potential applications in the health food and cosmetic industries, respectively. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  3. Flavonoids released by carrot (Daucus carota) seedlings stimulate hyphal development of vesicular-arbuscular mycorrhizal fungi in the presence of optimal CO2 enrichment.

    PubMed

    Poulin, M J; Bel-Rhlid, R; Piché, Y; Chênevert, R

    1993-10-01

    Carbon dioxide has been previously identified as a critical volatile factor that stimulates hyphal growth ofGigaspora margarita, a vesiculararbuscular mycorrhizal fungus, and we determined the optimal concentration at 2.0%. The beneficial effect of CO2 on fungal development is also visible in the presence of stimulatory (quercetin, myricetin) or inhibitory (naringenin) flavonoids. Sterile root exudates from carrot seedlings stimulate the hyphal development ofG. margarita in the presence of optimal CO2 enrichment. Three flavonols (quercetin, kaempferol, rutin or quercetin 3-rutinoside) and two flavones (apigenin, luteolin) were identified in carrot root exudates by means of HPLC retention time. Flavonols like quercetin and kaempferol are known to have stimulatory effects on hyphal growth ofG. margarita.

  4. Analysis of the essential oil of Origanum dubium growing wild in Cyprus. Investigation of its antioxidant capacity and antimicrobial activity.

    PubMed

    Karioti, A; Vrahimi-Hadjilouca, T; Droushiotis, D; Rancic, A; Hadjipavlou-Litina, D; Skaltsa, H

    2006-11-01

    The volatile composition of Origanum dubium in two different maturation stages has been studied. The essential oils were obtained by hydrodistillation in a modified Clevenger-type apparatus, and their analyses were performed by GC and GC-MS. Identification of the components was made by comparison of mass spectra and retention indices with literature records and by co-chromatography with authentic compounds. Carvacrol was shown to be the main constituent. The essential oils were evaluated for antimicrobial activity and proved to be active against all tested microorganisms. Furthermore, their potential antioxidant activity was investigated and found to be significant in scavenging O2-. The samples were further evaluated for inhibition of soybean lipoxygenase LOX and showed high inhibitory activity.

  5. Assessing Mongolian gerbil emotional behavior: effects of two shock intensities and response-independent shocks during an extended inhibitory-avoidance task.

    PubMed

    Hurtado-Parrado, Camilo; González-León, Camilo; Arias-Higuera, Mónica A; Cardona, Angelo; Medina, Lucia G; García-Muñoz, Laura; Sánchez, Christian; Cifuentes, Julián; Forigua, Juan Carlos; Ortiz, Andrea; Acevedo-Triana, Cesar A; Rico, Javier L

    2017-01-01

    Despite step-down inhibitory avoidance procedures that have been widely implemented in rats and mice to study learning and emotion phenomena, performance of other species in these tasks has received less attention. The case of the Mongolian gerbil is of relevance considering the discrepancies in the parameters of the step-down protocols implemented, especially the wide range of foot-shock intensities (i.e., 0.4-4.0 mA), and the lack of information on long-term performance, extinction effects, and behavioral patterning during these tasks. Experiment 1 aimed to (a) characterize gerbils' acquisition, extinction, and steady-state performance during a multisession (i.e., extended) step-down protocol adapted for implementation in a commercially-available behavioral package (Video Fear Conditioning System-MED Associates Fairfax, VT, USA), and (b) compare gerbils' performance in this task with two shock intensities - 0.5 vs. 1.0 mA-considered in the low-to-mid range. Results indicated that the 1.0 mA protocol produced more reliable and clear evidence of avoidance learning, extinction, and reacquisition in terms of increments in freezing and on-platform time as well as suppression of platform descent. Experiment 2 aimed to (a) assess whether an alternate protocol consisting of a random delivery of foot shocks could replicate the effects of Experiment 1 and (b) characterize gerbils' exploratory behavior during the step-down task (jumping, digging, rearing, and probing). Random shocks did not reproduce the effects observed with the first protocol. The data also indicated that a change from random to response-dependent shocks affects (a) the length of each visit to the platform, but not the frequency of platform descends or freezing time, and (b) the patterns of exploratory behavior, namely, suppression of digging and rearing, as well as increments in probing and jumping. Overall, the study demonstrated the feasibility of the extended step-down protocol for studying steady performance, extinction, and reacquisition of avoidance behavior in gerbils, which could be easily implemented in a commercially available system. The observation that 1.0 mA shocks produced a clear and consistent avoidance behavior suggests that implementation of higher intensities is unnecessary for reproducing aversive-conditioning effects in this species. The observed patterning of freezing, platform descents, and exploratory responses produced by the change from random to periodic shocks may relate to the active defensive system of the gerbil. Of special interest is the probing behavior, which could be interpreted as risk assessment and has not been reported in other rodent species exposed to step-down and similar tasks.

  6. Assessing Mongolian gerbil emotional behavior: effects of two shock intensities and response-independent shocks during an extended inhibitory-avoidance task

    PubMed Central

    González-León, Camilo; Arias-Higuera, Mónica A.; Cardona, Angelo; Medina, Lucia G.; García-Muñoz, Laura; Sánchez, Christian; Cifuentes, Julián; Forigua, Juan Carlos; Ortiz, Andrea; Acevedo-Triana, Cesar A.; Rico, Javier L.

    2017-01-01

    Despite step-down inhibitory avoidance procedures that have been widely implemented in rats and mice to study learning and emotion phenomena, performance of other species in these tasks has received less attention. The case of the Mongolian gerbil is of relevance considering the discrepancies in the parameters of the step-down protocols implemented, especially the wide range of foot-shock intensities (i.e., 0.4–4.0 mA), and the lack of information on long-term performance, extinction effects, and behavioral patterning during these tasks. Experiment 1 aimed to (a) characterize gerbils’ acquisition, extinction, and steady-state performance during a multisession (i.e., extended) step-down protocol adapted for implementation in a commercially-available behavioral package (Video Fear Conditioning System—MED Associates Fairfax, VT, USA), and (b) compare gerbils’ performance in this task with two shock intensities – 0.5 vs. 1.0 mA—considered in the low-to-mid range. Results indicated that the 1.0 mA protocol produced more reliable and clear evidence of avoidance learning, extinction, and reacquisition in terms of increments in freezing and on-platform time as well as suppression of platform descent. Experiment 2 aimed to (a) assess whether an alternate protocol consisting of a random delivery of foot shocks could replicate the effects of Experiment 1 and (b) characterize gerbils’ exploratory behavior during the step-down task (jumping, digging, rearing, and probing). Random shocks did not reproduce the effects observed with the first protocol. The data also indicated that a change from random to response-dependent shocks affects (a) the length of each visit to the platform, but not the frequency of platform descends or freezing time, and (b) the patterns of exploratory behavior, namely, suppression of digging and rearing, as well as increments in probing and jumping. Overall, the study demonstrated the feasibility of the extended step-down protocol for studying steady performance, extinction, and reacquisition of avoidance behavior in gerbils, which could be easily implemented in a commercially available system. The observation that 1.0 mA shocks produced a clear and consistent avoidance behavior suggests that implementation of higher intensities is unnecessary for reproducing aversive-conditioning effects in this species. The observed patterning of freezing, platform descents, and exploratory responses produced by the change from random to periodic shocks may relate to the active defensive system of the gerbil. Of special interest is the probing behavior, which could be interpreted as risk assessment and has not been reported in other rodent species exposed to step-down and similar tasks. PMID:29152417

  7. Skin permeation and retention of topical bead formulation containing tranexamic acid.

    PubMed

    Vijayakumar, Ajay; Baskaran, Rengarajan; Yoo, Bong Kyu

    2017-02-01

    The objective of this study is to develop a topical bead formulation of tranexamic acid (TA) which can be used concomitantly with laser treatment. The bead formulation of TA (TAB) was successfully prepared by fluidized bed drying method. Physicochemical properties of the TAB were evaluated in terms of chemical stability of TA and differential scanning calorimetry. TA in the bead was stable up to six months at 25°C and existed as amorphous state. In vitro skin permeation and in vivo skin retention of TA in the beads were significantly higher compared to a commercial product. When the bead was dissolved into distilled water and applied concomitantly with laser treatment, the amount of TA retained in the skin in the in vivo study was inversely proportional to the energy levels of laser treatment, indicating absorption into subcutaneous tissue and drainage to systemic circulation. Therefore, when laser treatment is used concomitantly with TAB, energy level should be very carefully monitored to avoid possible adverse events associated with systemic side effects of TA.

  8. Degradable Molybdenum Oxide Nanosheets with Rapid Clearance and Efficient Tumor Homing Capabilities as a Therapeutic Nanoplatform.

    PubMed

    Song, Guosheng; Hao, Jiali; Liang, Chao; Liu, Teng; Gao, Min; Cheng, Liang; Hu, Junqing; Liu, Zhuang

    2016-02-05

    Molybdenum oxide (MoOx) nanosheets with high near-infrared (NIR) absorbance and pH-dependent oxidative degradation properties were synthesized, functionalized with polyethylene glycol (PEG), and then used as a degradable photothermal agent and drug carrier. The nanosheets, which are relatively stable under acidic pH, could be degraded at physiological pH. Therefore, MoOx-PEG distributed in organs upon intravenous injection would be rapidly degraded and excreted without apparent in vivo toxicity. MoOx-PEG shows efficient accumulation in tumors, the acidic pH of which then leads to longer tumor retention of those nanosheets. Along with the capability of acting as a photothermal agent for effective tumor ablation, MoOx-PEG can load therapeutic molecules with high efficiencies. This concept of inorganic theranostic nanoagent should be relatively stable in tumors to allow imaging and treatment, while being readily degradable in normal organs to enable rapid excretion and avoid long-term retention/toxicity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Diffuse emission and control of copper in urban surface runoff.

    PubMed

    Boller, M A; Steiner, M

    2002-01-01

    Copper washed off from roofs and roads is considered to be a major contribution to diffuse copper pollution of urban environments. In order to guarantee sustainable protection of soils and water, the long-term strategy is to avoid or replace copper containing materials on roofs and fagades. Until achievement of this goal, a special adsorber system is suggested to control the diffuse copper fluxes by retention of copper by a mixture of granulated iron-hydroxide (GEH) and calcium carbonate. Since future stormwater runoff concepts are based on decentralised runoff infiltration into the underground, solutions are proposed which provide for copper retention in infiltration sites using GEH adsorption layers. The example of a large copper façade of which the runoff is treated in an adsorption trench reveals the first full-scale data on façade runoff and adsorber performance. During the first year of investigation average façade runoff concentrations in the range of 1-10 mg Cu/l are reduced by 96-99% in the adsorption ditch.

  10. The role of the dorsolateral prefrontal cortex in early threat processing: a TMS study.

    PubMed

    Sagliano, Laura; D'Olimpio, Francesca; Panico, Francesco; Gagliardi, Serena; Trojano, Luigi

    2016-12-01

    Previous studies demonstrated that excitatory (high frequency) offline transcranial magnetic stimulation (TMS) over the left and right dorsolateral prefrontal cortex (DLPFC) modulates attention allocation on threatening stimuli in non-clinical samples. These studies only employed offline TMS protocol that did not allow investigating the effect of the stimulation on the early stage of threat processing. In this study, the role of the right and left dorsolateral prefrontal cortex in early threat processing was investigated in high and low anxious individuals by means of an inhibitory single-pulse online TMS protocol. Our results demonstrated the role of the left DLPFC in an early stage of threat processing and that this effect is modulated by individuals' anxiety level. The inhibitory stimulation of the left DLPFC determined a disengagement bias in high anxious individuals, while the same stimulation determined an attentional avoidance in low anxious individuals. The findings of the present study suggest that right and left DLPFC are differently involved in early threat processing of healthy individuals. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control.

    PubMed

    Howard, Steven J; Okely, Anthony D

    2015-09-01

    Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted for young children. Given young children's comparatively limited cognitive capacities, however, such adaptations do not guarantee that the task's critical EF demands are retained. To investigate this possibility, the current study examined the characteristics that optimize measurement of young children's EFs-specifically, their inhibitory control-using the go/no-go (GNG) task as an exemplar. Sixty preschoolers completed six GNG tasks differing in stimulus animation, presentation time, and response location. Comparison EF tasks were administered to examine concurrent validity of GNG variants. Results indicated effects of stimulus presentation time and response location, with animation further enhancing task validity and reliability. This suggests that current GNG tasks deflate estimates of young children's ability to inhibit, with implications for future design and selection of developmentally appropriate EF tasks.

  12. Microbial biodiesel production from oil palm biomass hydrolysate using marine Rhodococcus sp. YHY01.

    PubMed

    Bhatia, Shashi Kant; Kim, Junyoung; Song, Hun-Seok; Kim, Hyun Joong; Jeon, Jong-Min; Sathiyanarayanan, Ganesan; Yoon, Jeong-Jun; Park, Kyungmoon; Kim, Yun-Gon; Yang, Yung-Hun

    2017-06-01

    The effect of various biomass derived inhibitors (i.e. furfural, hydroxymethylfurfural (HMF), vanillin, 4-hydroxy benzaldehyde (4-HB) and acetate) was investigated for fatty acid accumulation in Rhodococcus sp. YHY 01. Rhodococcus sp. YHY01 was able to utilize acetate, vanillin, and 4-HB for biomass production and fatty acid accumulation. The IC 50 value for furfural (3.1mM), HMF (3.2mM), vanillin (2.0mM), 4-HB (2.7mM) and acetate (3.7mM) was calculated. HMF and vanillin affect fatty acid composition and increase saturated fatty acid content. Rhodococcus sp. YHY 01 cultured with empty fruit bunch hydrolysate (EFBH) as the main carbon source resulted in enhanced biomass (20%) and fatty acid productivity (37%), in compression to glucose as a carbon source. Overall, this study showed the beneficial effects of inhibitory molecules on growth and fatty acid production, and support the idea of biomass hydrolysate utilization for biodiesel production by avoiding complex efforts to remove inhibitory compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Adolescent transformations of behavioral and neural processes as potential targets for prevention.

    PubMed

    Eldreth, Dana; Hardin, Michael G; Pavletic, Nevia; Ernst, Monique

    2013-06-01

    Adolescence is a transitional period in development that is marked by a distinct, typical behavioral profile of high rates of exploration, novelty-seeking, and emotional lability. While these behaviors generally assist the adolescent transition to independence, they can also confer vulnerability for excessive risk-taking and psychopathology, particularly in the context of specific environmental or genetic influences. As prevention research depends on the identification of targets of vulnerability, the following review will discuss the interplay among motivational systems including reward-related, avoidance-related, and regulatory processes in typical and atypical adolescent development. Each set of processes will be discussed in relation to their underlying neural correlates and distinct developmental trajectories. Evidence suggests that typical adolescent behavior and the risk for atypical development are mediated by heightened adolescent responsiveness of reward-related and avoidance-related systems under specific conditions, concurrent with poor modulation by immature regulatory processes. Finally, we will propose strategies to exploit heightened reward processing to reinforce inhibitory control, which is an essential component of regulatory processes in prevention interventions.

  14. Individual differences in heart rate variability are associated with the avoidance of negative emotional events.

    PubMed

    Katahira, Kentaro; Fujimura, Tomomi; Matsuda, Yoshi-Taka; Okanoya, Kazuo; Okada, Masato

    2014-12-01

    Although the emotional outcome of a choice generally affects subsequent decisions, humans can inhibit the influence of emotion. Heart rate variability (HRV) has emerged as an objective measure of individual differences in the capacity for inhibitory control. In the present study, we investigated how individual differences in HRV at rest are associated with the emotional effects of the outcome of a choice on subsequent decision making using a decision-making task in which emotional pictures appeared as decision outcomes. We used a reinforcement learning model to characterize the observed behaviors according to several parameters, namely, the learning rate and the motivational value of positive and negative pictures. Consequently, we found that individuals with a lower resting HRV exhibited a greater negative motivational value in response to negative pictures, suggesting that these individuals tend to avoid negative pictures compared with individuals with a higher resting HRV. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Effects of activation and blockade of dopamine receptors on the extinction of a passive avoidance reaction in mice with a depressive-like state.

    PubMed

    Dubrovina, N I; Zinov'eva, D V

    2010-01-01

    Learning and extinction of a conditioned passive avoidance reaction resulting from neuropharmacological actions on dopamine D(1) and D(2) receptors were demonstrated to be specific in intact mice and in mice with a depressive-like state. Learning was degraded only after administration of the D(2) receptor antagonist sulpiride and was independent of the initial functional state of the mice. In intact mice, activation of D(2) receptors with quinpirole led to a deficit of extinction, consisting of a reduction in the ability to acquire new inhibitory learning in conditions associated with the disappearance of the expected punishment. In mice with the "behavioral despair" reaction, characterized by delayed extinction, activation of D(1) receptors with SKF38393 normalized this process, while the D(2) agonist was ineffective. A positive effect consisting of accelerated extinction of the memory of fear of the dark ("dangerous") sector of the experimental chamber was also seen on blockade of both types of dopamine receptor.

  16. AMPA receptors mediate passive avoidance deficits induced by sleep deprivation.

    PubMed

    Dubiela, Francisco Paulino; Queiroz, Claudio Marcos; Moreira, Karin Di Monteiro; Nobrega, Jose N; Sita, Luciane Valéria; Tufik, Sergio; Hipolide, Debora Cristina

    2013-11-15

    The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Effects of caffeine on behavioural and cognitive deficits in rats.

    PubMed

    Assis, Melissa S; Soares, Aluízio C; de Sousa, Dircilei N; Eudes-Filho, João; Faro, Lilian Rosana F; Carneiro, Fabiana P; da Silva, Mônica V; Motoyama, Andrea B; de Souza, Greice Maria R; Marchiori, Stéphanie; de Lima, Nadyelle T; Boëchat-Barros, Raphael; Ferreira, Vania M

    2018-05-07

    There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the cecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long-term behavioural and cognitive deficits induced by CLP. On the last day, one hour after caffeine administration, the animals were submitted to open-field, elevated plus-maze (EPM), forced swimming, and step-down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham-operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis-surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Interactions of nitric oxide with α2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine.

    PubMed

    Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M; Ugale, Rajesh R

    2016-09-01

    Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra-LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S-nitrosoglutathione, non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), the α2 -adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra-LC before agmatine. Intra-hippocampal injections of the NMDA antagonist, MK-801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Agmatine (intra-LC or i.p.) facilitated memory retrieval in the IA test. S-nitrosoglutathione potentiated, while L-NAME and L-NIO decreased, these effects of agmatine. L-NIL and 7-NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S-nitrosoglutathione and yohimbine were blocked by intra-hippocampal MK-801. Agmatine increased the population of TH- and eNOS-immunoreactive elements in the LC. The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. © 2016 The British Pharmacological Society.

  19. Interactions of nitric oxide with α2‐adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine

    PubMed Central

    Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M

    2016-01-01

    Background and Purpose Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α‐adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. Experimental Approach The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra‐LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S‐nitrosoglutathione, non‐specific (L‐NAME) and specific NOS inhibitors (L‐NIL, 7‐NI, L‐NIO), the α2‐adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra‐LC before agmatine. Intra‐hippocampal injections of the NMDA antagonist, MK‐801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Key Results Agmatine (intra‐LC or i.p.) facilitated memory retrieval in the IA test. S‐nitrosoglutathione potentiated, while L‐NAME and L‐NIO decreased, these effects of agmatine. L‐NIL and 7‐NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S‐nitrosoglutathione and yohimbine were blocked by intra‐hippocampal MK‐801. Agmatine increased the population of TH‐ and eNOS‐immunoreactive elements in the LC. Conclusions and Implications The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. PMID:27273730

  20. The different effects of lithium and tamoxifen on memory formation and the levels of neurotrophic factors in the brain of male and female rats.

    PubMed

    Valvassori, Samira S; Borges, Cenita P; Varela, Roger B; Bavaresco, Daniela V; Bianchini, Guilherme; Mariot, Edemilson; Arent, Camila O; Resende, Wilson R; Budni, Josiane; Quevedo, João

    2017-09-01

    Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats. Copyright © 2017. Published by Elsevier Inc.

  1. NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice.

    PubMed

    Freudenthal, Ramiro; Boccia, Mariano M; Acosta, Gabriela B; Blake, Mariano G; Merlo, Emiliano; Baratti, Carlos M; Romano, Arturo

    2005-05-01

    Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of the Rel/nuclear factor-kappaB (NF-kappaB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kappaB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pretraining administration of a double-stranded DNA oligonucleotide containing the NF-kappaB consensus sequence (kappaB decoy). Conversely, one base mutation of the kappaB decoy (mut-kappaB decoy) injection did not affect long-term memory. Accordingly, the kappaB decoy inhibited NF-kappaB in hippocampus 2 h after injection but no inhibition was found with mut-kappaB decoy administration. A temporal course of hippocampal NF-kappaB activity after training was determined. Unexpectedly, an inhibition of NF-kappaB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-kappaB was activated 45 min after training in both shocked and unshocked groups, decreasing 1 h after training and returning to basal levels 2 and 4 h after training. On the basis of the latter results, we propose that activation of NF-kappaB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitute the conditioned stimulus representation. The results presented here provide the first evidence to support NF-kappaB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.

  2. Effect of harmane, an endogenous β-carboline, on learning and memory in rats.

    PubMed

    Celikyurt, Ipek Komsuoglu; Utkan, Tijen; Gocmez, Semil Selcen; Hudson, Alan; Aricioglu, Feyza

    2013-01-01

    Our aim was to investigate the effects of acute harmane administration upon learning and memory performance of rats using the three-panel runway paradigm and passive avoidance test. Male rats received harmane (2.5, 5, and 7.5mg/kg, i.p.) or saline 30 min. before each session of experiments. In the three panel runway paradigm, harmane did not affect the number of errors and latency in reference memory. The effect of harmane on the errors of working memory was significantly higher following the doses of 5mg/kg and 7.5mg/kg. The latency was changed significantly at only 7.5mg/kg in comparison to control group. Animals were given pre-training injection of harmane in the passive avoidance test in order to determine the learning function. Harmane treatment decreased the retention latency significantly and dose dependently, which indicates an impairment in learning. In this study, harmane impaired working memory in three panel runway test and learning in passive avoidance test. As an endogenous bioactive molecule, harmane might have a critical role in the modulation of learning and memory functions. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Evolution of post-ESWL residual lithiasis depending on the type of calculus and urine composition.

    PubMed

    Grases, Felix; Costa-Bauzá, Antonia; Isern, Bernat; Sanchis, Pilar; Perelló, Joan; Hierro, Fernando; Conte Visus, Antonio

    2009-07-01

    Extracorporeal shock wave lithotripsy (ESWL) is one of the most commonly used procedures for removal of renal calculi from the upper urinary tract, but complete expulsion of the fragments generated is not always achieved. This can lead to new lithiasic episodes, and it is considered that 10-26% of fragmented calculi can undergo regrowth. This in vitro study investigated the influence of fragment and urinary composition on post-ESWL growth of fragments, with the aims of establishing the effect and importance of these parameters, and identifying effective prophylactic measures. Fragments collected from patients immediately following expulsion after ESWL treatment were selected for regrowth experiments. The particles included 24 calcium oxalate monohydrate (COM) fragments, 48 calcium oxalate dihydrate (COD), 24 hydroxyapatite (HAP), and 16 uric acid. In all treatments, calculi fragments showed a considerable capacity to induce growth of calcium oxalate and calcium phosphate. Under normocalciuria conditions, new COM crystals formed; both COM and COD crystals developed under hypercalciuria conditions at a urinary pH < 6.0; and in hypercalciuric conditions and urinary pH > 6.0 both HAP and brushite (BRU) crystals were formed. The highest growth rates were observed for COD calculi fragments under hypercalciuria conditions and at a urinary pH of 6.5, followed by growth on COM and HAP fragments under the same conditions; growth rates under other conditions tested were similar but 10-fold lower. With regard to the role of crystallization inhibitors, phytate exhibited inhibitory effects under all assay conditions. However, citrate had little effect, even at the highest concentration tested (1,000 mg/L). This study demonstrates the importance of avoiding heterogeneous nucleant retention (pre-existing solid microparticles) in renal cavities, as these can act as very efficient inducers of the formation of new calculi, the composition of which is mainly dependant on the urine composition.

  4. Involvement of protein kinase C in the modulation of morphine-induced analgesia and the inhibitory effects of exposure to 60-hz magnetic fields in the land snail, Cepaea nemoralis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kavaliers, M.; Ossenkopp, K.P.

    1990-02-26

    One of the more consistent and dramatic effects of exposure to magnetic fields is the attenuation of morphine-induced analgesia. Results of previous studies have implicated alterations in calcium channel functioning and Ca{sup ++} flux in the mediation of these effects. It is generally accepted that Ca{sup ++}-activated-phospholipid-dependent protein kinase (Protein kinase C; PKC) plays an important role in relaying trans-membrane signaling in diverse Ca{sup ++} dependent cellular processes. In experiment 1 we observed that morphine-induced analgesia in the land snail, Cepaea nemoralis, as measured by the latency of an avoidance behavior to a warmed surface, was reduced by the PKCmore » activator, SC-9, and was enhanced by the PKC inhibitors, H-7 and H-9. In contrast, HA-10004, a potent inhibitor of other protein kinases, but only a very weak inhibitor of PKC, had no effect on morphine-induced analgesia. In experiment 2 exposure of snails for 30 minutes to a 1.0 gauss (rms) 60-Hz magnetic field reduced morphine-induced analgesia. This inhibitory effect of the magnetic field was reduced by the PKC inhibitors, H-7 and H-9, and was augmented by the PKC activator SC-9. These results suggest that: (i) PKC is involved in the modulation of morphine-induced analgesia and, (ii) the inhibitory effects of magnetic fields involve PKC.« less

  5. Evidence for superior neurobiological and behavioral inhibitory control abilities in non-offending as compared to offending pedophiles.

    PubMed

    Kärgel, Christian; Massau, Claudia; Weiß, Simone; Walter, Martin; Borchardt, Viola; Krueger, Tillmann H C; Tenbergen, Gilian; Kneer, Jonas; Wittfoth, Matthias; Pohl, Alexander; Gerwinn, Hannah; Ponseti, Jorge; Amelung, Till; Beier, Klaus M; Mohnke, Sebastian; Walter, Henrik; Schiffer, Boris

    2017-02-01

    Neurobehavioral models of pedophilia and child sexual offending suggest a pattern of temporal and in particular prefrontal disturbances leading to inappropriate behavioral control and subsequently an increased propensity to sexually offend against children. However, clear empirical evidence for such mechanisms is still missing. Using a go/nogo paradigm in combination with functional magnetic resonance imaging (fMRI) we compared behavioral performance and neural response patterns among three groups of men matched for age and IQ: pedophiles with (N = 40) and without (N = 37) a history of hands-on sexual offences against children as well as healthy non-offending controls (N = 40). As compared to offending pedophiles, non-offending pedophiles exhibited superior inhibitory control as reflected by significantly lower rate of commission errors. Group-by-condition interaction analysis also revealed inhibition-related activation in the left posterior cingulate and the left superior frontal cortex that distinguished between offending and non-offending pedophiles, while no significant differences were found between pedophiles and healthy controls. Both areas showing distinct activation pattern among pedophiles play a critical role in linking neural networks that relate to effective cognitive functioning. Data therefore suggest that heightened inhibition-related recruitment of these areas as well as decreased amount of commission errors is related to better inhibitory control in pedophiles who successfully avoid committing hands-on sexual offences against children. Hum Brain Mapp 38:1092-1104, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Isolation of quercetin and mandelic acid from Aesculus indica fruit and their biological activities.

    PubMed

    Zahoor, Muhammad; Shafiq, Sadaf; Ullah, Habib; Sadiq, Abdul; Ullah, Farhat

    2018-06-26

    In this study Aesculus indica fruit was subjected to isolation of phytochemicals. Two antioxidants quercetin and Mandelic acid were isolated in pure state. The free radical scavenging and acetyl choline esterase inhibitory potential of the crude extract and sub fractions were also determined. The antioxidant capacity of crude extract, fractions and isolated compounds were determined by DPPH and ABTS methods. Folin-Ciocalteu reagent method was used to estimate the total phenolic contents and were found to be 78.34 ± 0.96, 44.16 ± 1.05, 65.45 ± 1.29, 37.85 ± 1.44 and 50.23 ± 2.431 (mg/g of gallic acid) in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fractions respectively. The flavonoid concentration in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fraction were; 85.30 ± 1.20, 53.80 ± 1.07, 77.50 ± 1.12, 26.30 ± 1.35 and 37.78 ± 1.25 (mg/g of quercetin) respectively. The chloroform fraction was more potent against enzymes, acetyl choline esterase and butyryl choline esterase (IC 50  = 85 and 160 μg/ml respectively). The phenolic compounds in the crude extract and fractions were determined using HPLC standard method. Chlorogenic acid, quercetin, phloroglucinol, rutin, mandelic acid and hydroxy benzoic acid were detected at retention times 6.005, 10.062, 22.623, 30.597, 35.490 and 36.211 in crude extract and different fractions. The ethyl acetate fraction was rich in the targeted compounds and was therefore subjected to column isolation. The HPLC chromatogram of isolated compounds showed single peak at specified retention times which confirms their isolation in pure state. The isolated compounds were then characterized by FTIR and NMR spectrophotometric techniques. The Aesculus indica fruit extracts showed antioxidant and anticholine esterase inhibitory potentials. Two bioactive compounds were isolated in the pure form ethyl acetate fraction. From results it was concluded that the fruit of this plant could be used to minimize oxidative stress caused by reactive oxygen species.

  7. SSP-002392, a new 5-HT4 receptor agonist, dose-dependently reverses scopolamine-induced learning and memory impairments in C57Bl/6 mice.

    PubMed

    Lo, Adrian C; De Maeyer, Joris H; Vermaercke, Ben; Callaerts-Vegh, Zsuzsanna; Schuurkes, Jan A J; D'Hooge, Rudi

    2014-10-01

    5-HT4 receptors (5-HT4R) are suggested to affect learning and memory processes. Earlier studies have shown that animals treated with 5-HT4R agonists, often with limited selectivity, show improved learning and memory with retention memory often being assessed immediately after or within 24 h after the last training session. In this study, we characterized the effect of pre-training treatment with the selective 5-HT4R agonist SSP-002392 on memory acquisition and the associated long-term memory retrieval in animal models of impaired cognition. Pre-training treatment with SSP-002392 (0.3 mg/kg, 1.5 mg/kg and 7.5 mg/kg p.o.) dose-dependently inhibited the cognitive deficits induced by scopolamine (0.5 mg/kg s.c.) in two different behavioral tasks: passive avoidance and Morris water maze. In the Morris water maze, spatial learning was significantly improved after treatment with SSP-002392 translating in an accelerated and more efficient localization of the hidden platform compared to scopolamine-treated controls. Moreover, retention memory was assessed 24 h (passive avoidance) and 72 h (Morris water maze) after the last training session of cognitive-impaired animals and this was significantly improved in animals treated with SSP-002392 prior to the training sessions. Furthermore, the effects of SSP-002392 were comparable to galanthamine hydrobromide. We conclude that SSP-002392 has potential as a memory-enhancing compound. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Assessing the Financial Value of Patient Engagement: A Quantitative Approach from CTTI's Patient Groups and Clinical Trials Project.

    PubMed

    Levitan, Bennett; Getz, Kenneth; Eisenstein, Eric L; Goldberg, Michelle; Harker, Matthew; Hesterlee, Sharon; Patrick-Lake, Bray; Roberts, Jamie N; DiMasi, Joseph

    2018-03-01

    While patient groups, regulators, and sponsors are increasingly considering engaging with patients in the design and conduct of clinical development programs, sponsors are often reluctant to go beyond pilot programs because of uncertainty in the return on investment. We developed an approach to estimate the financial value of patient engagement. Expected net present value (ENPV) is a common technique that integrates the key business drivers of cost, time, revenue, and risk into a summary metric for project strategy and portfolio decisions. We assessed the impact of patient engagement on ENPV for a typical oncology development program entering phase 2 or phase 3. For a pre-phase 2 project, the cumulative impact of a patient engagement activity that avoids one protocol amendment and improves enrollment, adherence, and retention is an increase in net present value (NPV) of $62MM ($65MM for pre-phase 3) and an increase in ENPV of $35MM ($75MM for pre-phase 3). Compared with an investment of $100,000 in patient engagement, the NPV and ENPV increases can exceed 500-fold the investment. This ENPV increase is the equivalent of accelerating a pre-phase 2 product launch by 2½ years (1½ years for pre-phase 3). Risk-adjusted financial models can assess the impact of patient engagement. A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrollment, adherence, and retention may add considerable financial value. This approach can help sponsors assess patient engagement investment decisions.

  9. Caffeine impairs the acquisition and retention, but not the consolidation of Pavlovian conditioned freezing in mice

    PubMed Central

    Dubroqua, Sylvain; Low, Samuel R.L.; Yee, Benjamin K.; Singer, Philipp

    2014-01-01

    Rationale The psychoactive substance, caffeine may improve cognitive performance, but its direct impact on learning and memory remains ill-defined. Conflicting reports suggest that caffeine may impair as well as enhance Pavlovian fear conditioning in animals, and its effect may vary across different phases of learning. Objectives To dissect the effect of a motor-stimulant dose of caffeine (30 mg/kg i.p.) on acquisition, retrieval or consolidation of conditioned fear in C57BL/6 mice. Methods Fear conditioning was evaluated in a conditioned freezing paradigm comprising 3 tone-shock pairings and a two-way active avoidance paradigm lasting two consecutive days with 80 conditioning trials per test session. Results Conditioning to both the discrete tone conditioned stimulus (CS) and the context was markedly impaired by caffeine. The deficits were similarly evident when caffeine was administered prior to acquisition or retrieval (48 and 72 h after conditioning); and the most severe impairment was seen in animals given caffeine before acquisition and before retrieval. A comparable deficit was observed in the conditioned active avoidance test. By contrast, caffeine administered immediately following acquisition neither affected the expression of tone freezing nor context freezing. Conclusions The present study challenges the previous report that caffeine primarily disrupts hippocampus-dependent conditioning to the context. At the relevant dose range, acute caffeine likely exerts more widespread impacts beyond the hippocampus, including amygdala and striatum that are anatomically connected to the hippocampus; and together they support the acquisition and retention of fear memories to discrete stimuli as well as diffused contextual cues. PMID:25172668

  10. Assessing the Financial Value of Patient Engagement

    PubMed Central

    Levitan, Bennett; Getz, Kenneth; Eisenstein, Eric L.; Goldberg, Michelle; Harker, Matthew; Hesterlee, Sharon; Patrick-Lake, Bray; Roberts, Jamie N.; DiMasi, Joseph

    2017-01-01

    Background: While patient groups, regulators, and sponsors are increasingly considering engaging with patients in the design and conduct of clinical development programs, sponsors are often reluctant to go beyond pilot programs because of uncertainty in the return on investment. We developed an approach to estimate the financial value of patient engagement. Methods: Expected net present value (ENPV) is a common technique that integrates the key business drivers of cost, time, revenue, and risk into a summary metric for project strategy and portfolio decisions. We assessed the impact of patient engagement on ENPV for a typical oncology development program entering phase 2 or phase 3. Results: For a pre–phase 2 project, the cumulative impact of a patient engagement activity that avoids one protocol amendment and improves enrollment, adherence, and retention is an increase in net present value (NPV) of $62MM ($65MM for pre–phase 3) and an increase in ENPV of $35MM ($75MM for pre–phase 3). Compared with an investment of $100,000 in patient engagement, the NPV and ENPV increases can exceed 500-fold the investment. This ENPV increase is the equivalent of accelerating a pre–phase 2 product launch by 2½ years (1½ years for pre–phase 3). Conclusions: Risk-adjusted financial models can assess the impact of patient engagement. A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrollment, adherence, and retention may add considerable financial value. This approach can help sponsors assess patient engagement investment decisions. PMID:29714515

  11. Insights into arsenic retention dynamics of Pleistocene aquifer sediments by in situ sorption experiments.

    PubMed

    Neidhardt, Harald; Winkel, Lenny H E; Kaegi, Ralf; Stengel, Caroline; Trang, Pham T K; Lan, Vi M; Viet, Pham H; Berg, Michael

    2018-02-01

    The migration of arsenic (As) enriched groundwater into Pleistocene aquifers as a consequence of extensive groundwater abstraction represents an increasing threat to the precious water resources in Asian delta regions. Pleistocene aquifer sediments are typically rich in FeIII-(hydr)oxides and are capable to adsorb high amounts of As. This results in a pronounced accumulation of As in Pleistocene aquifers, where high As groundwater infiltrates from adjacent Holocene aquifers. However, As retention by Pleistocene aquifers over long-term time scales remains largely unknown. We studied As sorption in situ by placing natural Pleistocene sediments and pure mineral phases directly inside groundwater monitoring wells at a study site near Hanoi (Vietnam). This in situ exposure allows for constant flushing of the samples with unaltered groundwater and the establishment of undisturbed sorption equilibria similar to those in local aquifer sediments, which is not readily attainable in traditional laboratory sorption experiments. The groundwaters in our experimental wells were characterized by different As concentrations (0.01-6.63 μmol/L) and redox states, reaching from suboxic to anoxic conditions (E h of +159 to -4 mV). Results show that adsorption is the dominant As retention mechanism, independent from the respective groundwater chemistry (i.e. concentrations of dissolved P, HCO 3 - and Si). Whilst most of the As sorbed within the first week, sorption further increased slowly but consistently by 6-189%, respectively, within six months. Hence, the As sorption behavior of Pleistocene aquifer sediments should be determined over longer periods to avoid an underestimation of the As sorption capacity. Accompanying desorption experiments revealed that about 51% of the sorbed As was remobilized within six months when exposed to low As groundwater. We therefore conclude that a considerable proportion of the As accumulated in the aquifer sediments is prone to remobilization once the As concentrations in migrating groundwater decline. Remobilization of As should be considered in local water management plans to avoid contamination of precious groundwater resources with this As legacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice.

    PubMed

    Lemos, Mayra Tolentino Resk; Amaral, Fabio Agostini; Dong, Karis Ester; Bittencourt, Maria Fernanda Queiroz Prado; Caetano, Ariadiny Lima; Pesquero, João Bosco; Viel, Tania Araujo; Buck, Hudson Sousa

    2010-04-01

    Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer's disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer's disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n=10 per group) were submitted to an acquisition session, reinforcement to learning (24h later: test 1) and final test (7days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/-2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, P<0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P<0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P<0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P<0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. Copyright 2009 Elsevier Ltd. All rights reserved.

  13. Small pelagic fish reproductive strategies in upwelling systems: A natal homing evolutionary model to study environmental constraints

    NASA Astrophysics Data System (ADS)

    Brochier, T.; Colas, F.; Lett, C.; Echevin, V.; Cubillos, L. A.; Tam, J.; Chlaida, M.; Mullon, C.; Fréon, P.

    2009-12-01

    Although little is known about the individual-level mechanisms that influence small pelagic fish species’ reproductive strategy, Mullon et al. [Mullon, C., Cury, P., Penven, P., 2002. Evolutionary individual-based model for the recruitment of anchovy ( Engraulis capensis) in the southern Benguela. Canadian Journal of Fisheries and Aquatic Sciences 59, 910-922] showed that the observed anchovy spawning patterns in the southern Benguela Current system off South Africa could be accurately reproduced by simulating a natal homing reproductive strategy, i.e. individuals spawning at their natal date and place. Here we used a similar method, i.e., an individual-based model of the natal homing reproductive strategy, and applied it to other upwelling systems: the northern Humboldt Current system off Peru, the southern Humboldt Current system off Chile and the central Canary Current system off Morocco. We investigated the spatial (horizontal and vertical) and seasonal spawning patterns that emerged after applying different environmental constraints in the model, and compared these to observed spawning patterns of sardine and anchovy in their respective systems. The selective environmental constraints tested were: (1) lethal temperature; (2) retention over the continental shelf; and (3) avoidance of dispersive structures. Simulated horizontal spatial patterns and seasonal patterns compared reasonably well with field data, but vertical patterns in most cases did not. Similarly to what was found for the southern Benguela, temperature was a determinant constraint in the southern Humboldt. The shelf retention constraint led to selection of a particular spawning season during the period of minimum upwelling in all three of the upwelling regions considered, and to spatial patterns that matched observed anchovy spawning off Chile and sardine spawning off Morocco. The third constraint, avoidance of dispersive structures, led to the emergence of a spawning season during the period of maximum upwelling off Chile and Morocco, but not in Peru. The most accurate representation of observed spatio-temporal spawning patterns off Peru was achieved through a combination of shelf retention and non-dispersion constraints.

  14. Does microbial resistance to biocides create a hazard to food hygiene?

    PubMed

    Meyer, Bernhard

    2006-12-01

    Numerous reports are available on microbial resistance to antibiotics as well as to biocides. Instances of cross-resistance between these substance groups have been reported. Resistance, which is a genetically determined phenomenon, has to be distinguished from phenotypic adaptation processes, which are not hereditary. Adaptation can be avoided by rigorous cleaning and disinfection, avoiding concentrations of disinfectants below the microbicidal concentration. Resistance phenomena have to be divided into intrinsic and acquired resistance. Intrinsic resistance is the naturally greater resistance of certain microbial species compared to others. The term acquired resistance is used if certain strains of a microbial species differ significantly in their susceptibility to biocides compared to the average of this species. An overview of existing reports of resistance to different biocidal substances is given. In most of these reports, resistance is defined as an elevated minimum inhibitory concentration. The relevance of these data for disinfection processes, where microbicidal concentrations are applied, is discussed. Rotational use of different types of disinfectants, to avoid development of resistance, has been discussed controversially. Because of the unspecific mechanism of action of biocides, and the lack of scientific evidence for its need, rotational use of disinfectants is not recommended. In conclusion the risk of hazards in food production and processing caused by resistance to biocides is regarded as low.

  15. Prediction of soil organic carbon partition coefficients by soil column liquid chromatography.

    PubMed

    Guo, Rongbo; Liang, Xinmiao; Chen, Jiping; Wu, Wenzhong; Zhang, Qing; Martens, Dieter; Kettrup, Antonius

    2004-04-30

    To avoid the limitation of the widely used prediction methods of soil organic carbon partition coefficients (KOC) from hydrophobic parameters, e.g., the n-octanol/water partition coefficients (KOW) and the reversed phase high performance liquid chromatographic (RP-HPLC) retention factors, the soil column liquid chromatographic (SCLC) method was developed for KOC prediction. The real soils were used as the packing materials of RP-HPLC columns, and the correlations between the retention factors of organic compounds on soil columns (ksoil) and KOC measured by batch equilibrium method were studied. Good correlations were achieved between ksoil and KOC for three types of soils with different properties. All the square of the correlation coefficients (R2) of the linear regression between log ksoil and log KOC were higher than 0.89 with standard deviations of less than 0.21. In addition, the prediction of KOC from KOW and the RP-HPLC retention factors on cyanopropyl (CN) stationary phase (kCN) was comparatively evaluated for the three types of soils. The results show that the prediction of KOC from kCN and KOW is only applicable to some specific types of soils. The results obtained in the present study proved that the SCLC method is appropriate for the KOC prediction for different types of soils, however the applicability of using hydrophobic parameters to predict KOC largely depends on the properties of soil concerned.

  16. Stability of Balloon-Retention Gastrostomy Tubes with Different Concentrations of Contrast Material: In Vitro Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lopera, Jorge E., E-mail: Lopera@uthscsa.ed; Alvarez, Alex; Trimmer, Clayton

    2009-01-15

    The purpose of this study was to determine the performance of two balloon-retention-type gastrostomy tubes when the balloons are inflated with two types of contrast materials at different concentrations. Two commonly used balloon-retention-type tubes (MIC and Tri-Funnel) were inflated to the manufacturer's recommended volumes (4 and 20 cm{sup 3}, respectively) with normal saline or normal saline plus different concentrations of contrast material. Five tubes of each brand were inflated with normal saline and 0%, 25%, 50%, 75%, and 100% contrast material dilutions, using either nonionic hyperosmolar contrast, or nonionic iso-osmolar contrast. The tubes were submerged in a glass basin containingmore » a solution with a pH of 4. Every week the tubes were visually inspected to determine the integrity of the balloons, and the diameter of the balloons was measured with a caliper. The tests were repeated every week for a total of 12 weeks. The MIC balloons deflated slightly faster over time than the Tri-Funnel balloons. The Tri-Funnel balloons remained relatively stable over the study period for the different concentrations of contrast materials. The deflation rates of the MIC balloons were proportionally related to the concentration of saline and inversely related to the concentration of the contrast material. At high contrast material concentrations, solidification of the balloons was observed. In conclusion, this in vitro study confirms that the use of diluted amounts of nonionic contrast materials is safe for inflating the balloons of two types of balloon-retention feeding tubes. High concentrations of contrast could result in solidification of the balloons and should be avoided.« less

  17. Tramadol state-dependent memory: involvement of dorsal hippocampal muscarinic acetylcholine receptors.

    PubMed

    Jafari-Sabet, Majid; Jafari-Sabet, Ali-Reza; Dizaji-Ghadim, Ali

    2016-08-01

    The effects on tramadol state-dependent memory of bilateral intradorsal hippocampal (intra-CA1) injections of physostigmine, an acetylcholinesterase inhibitor, and atropine, a muscarinic acetylcholine receptor antagonist, were examined in adult male NMRI mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention. Post-training intra-CA1 administration of an atypical μ-opioid receptor agonist, tramadol (0.5 and 1 μg/mouse), dose dependently impaired memory retention. Pretest injection of tramadol (0.5 and 1 μg/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under the influence of post-training tramadol (1 μg/mouse, intra-CA1). A pretest intra-CA1 injection of physostigmine (1 μg/mouse) reversed the memory impairment induced by post-training administration of tramadol (1 μg/mouse, intra-CA1). Moreover, pretest administration of physostigmine (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of tramadol (0.25 μg/mouse, intra-CA1) also significantly restored retrieval. Pretest administration of physostigmine (0.25, 0.5, and 1 μg/mouse, intra-CA1) by itself did not affect memory retention. A pretest intra-CA1 injection of the atropine (1 and 2 μg/mouse) 5 min before the administration of tramadol (1 μg/mouse, intra-CA1) dose dependently inhibited tramadol state-dependent memory. Pretest administration of atropine (0.5, 1, and 2 μg/mouse, intra-CA1) by itself did not affect memory retention. It can be concluded that dorsal hippocampal muscarinic acetylcholine receptor mechanisms play an important role in the modulation of tramadol state-dependent memory.

  18. Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation

    PubMed Central

    Schneider, Craig S.; Xu, Qingguo; Boylan, Nicholas J.; Chisholm, Jane; Tang, Benjamin C.; Schuster, Benjamin S.; Henning, Andreas; Ensign, Laura M.; Lee, Ethan; Adstamongkonkul, Pichet; Simons, Brian W.; Wang, Sho-Yu S.; Gong, Xiaoqun; Yu, Tao; Boyle, Michael P.; Suk, Jung Soo; Hanes, Justin

    2017-01-01

    Mucoadhesive particles (MAP) have been widely explored for pulmonary drug delivery because of their perceived benefits in improving particle residence in the lungs. However, retention of particles adhesively trapped in airway mucus may be limited by physiologic mucus clearance mechanisms. In contrast, particles that avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized would provide prolonged lung retention compared to MAP. We compared in vivo behaviors of variously sized, polystyrene-based MAP and MPP in the lungs following inhalation. MAP, regardless of particle size, were aggregated and poorly distributed throughout the airways, leading to rapid clearance from the lungs. Conversely, MPP as large as 300 nm exhibited uniform distribution and markedly enhanced retention compared to size-matched MAP. On the basis of these findings, we formulated biodegradable MPP (b-MPP) with an average diameter of <300 nm and examined their behavior following inhalation relative to similarly sized biodegradable MAP (b-MAP). Although b-MPP diffused rapidly through human airway mucus ex vivo, b-MAP did not. Rapid b-MPP movements in mucus ex vivo correlated to a more uniform distribution within the airways and enhanced lung retention time as compared to b-MAP. Furthermore, inhalation of b-MPP loaded with dexamethasone sodium phosphate (DP) significantly reduced inflammation in a mouse model of acute lung inflammation compared to both carrier-free DP and DP-loaded MAP. These studies provide a careful head-to-head comparison of MAP versus MPP following inhalation and challenge a long-standing dogma that favored the use of MAP for pulmonary drug delivery. PMID:28435870

  19. The effect of denture adhesives on Candida albicans growth in vitro.

    PubMed

    Sampaio-Maia, Benedita; Figueiral, Maria Helena; Sousa-Rodrigues, Patricia; Fernandes, Maria Helena; Scully, Crispian

    2012-06-01

    Denture-wearing favours the growth of Candida. In view of the fact that many denture wearers regularly use adhesives to enhance denture retention, stability and function, the aim of this work was to study the effect of denture adhesives on Candida albicans growth in vitro. The denture adhesives tested were Corega(®) cream, Kukident(®) cream, Novafix(®) cream, Polident(®) cream, Protefix(®) cream, Steradent(®) cream, Aderyn(®) powder, Corega(®) ultra powder, Protefix(®) powder and Corega(®) strip. C. albicans growth curves were obtained in the presence or absence of a 1% solution of the denture adhesive diluted in Sabouraud broth. Macro- and microscopic morphological changes in C. albicans were analysed, as was microbial contamination of the denture adhesive. Most of the denture adhesives studied induced morphological changes in C. albicans cells and colonies, but only two had any significant inhibitory effect on yeast growth. Kukident(®) cream markedly inhibited C. albicans growth in a concentration-dependent way, reducing the growth rate by 95%, whereas Corega(®) cream also inhibited C. albicans growth but in a non-concentration-dependent way, reducing the growth rate by 37%. In addition, denture adhesives available as powders had detectable microbial contamination. Some commercially available denture adhesives showed microbial contamination and some had significant inhibitory effect on C. albicans growth. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

  20. Memotain: A CAD/CAM nickel-titanium lingual retainer.

    PubMed

    Kravitz, Neal D; Grauer, Dan; Schumacher, Pascal; Jo, Yong-Min

    2017-04-01

    Approximately 1/2 of maxillary and 1/5 of mandibular multi-stranded lingual retainers fail during retention in some form, either bond failure or wire breakage. Memotain is a new CAD/CAM fabricated lingual retainer wire made of custom-cut nickel-titanium, as an alternative to multi-stranded lingual retainers. It offers numerous perceived advantages to the traditional multi-stranded stainless steel wire, including precision fit, avoidance of interferences, corrosion resistance and even the potential for minor tooth movement as an active lingual retainer. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  1. Rectal ulcer in a patient with VZV sacral meningoradiculitis (Elsberg syndrome).

    PubMed

    Matsumoto, Hideyuki; Shimizu, Takahiro; Tokushige, Shin-ichi; Mizuno, Hideo; Igeta, Yukifusa; Hashida, Hideji

    2012-01-01

    This report describes the case of a 55-year-old woman with varicella-zoster virus (VZV) sacral meningoradiculitis (Elsberg syndrome) who presented with herpes zoster in the left S2 dermatome area, urinary retention, and constipation. Lumbar magnetic resonance imaging showed the left sacral nerve root swelling with enhancement. Thereafter, she suddenly showed massive hematochezia and hemorrhagic shock because of a rectal ulcer. To elucidate the relation between Elsberg syndrome and rectal ulcer, accumulation of similar cases is necessary. To avoid severe complications, attention must be devoted to the possibility of rectal bleeding in the early stage of Elsberg syndrome.

  2. Retention of stored water enables tropical tree saplings to survive extreme drought conditions.

    PubMed

    Wolfe, Brett T

    2017-04-01

    Trees generally maintain a small safety margin between the stem water potential (Ψstem) reached during seasonal droughts and the Ψstem associated with their mortality. This pattern may indicate that species face similar mortality risk during extreme droughts. However, if tree species vary in their ability to regulate Ψstem, then safety margins would poorly predict drought mortality. To explore variation among species in Ψstem regulation, I subjected potted saplings of six tropical tree species to extreme drought and compared their responses with well-watered plants and pretreatment reference plants. In the drought treatment, soil water potential reached <-10 MPa, yet three species, Bursera simaruba (L.) Sarg., Cavanillesia platanifolia (Bonpl.) Kunth and Cedrela odorata L. had 100% survival and maintained Ψstem near -1 MPa (i.e., desiccation-avoiding species). Three other species, Cojoba rufescens (Benth.) Britton and Rose, Genipa americana L. and Hymenaea courbaril L. had 50%, 0% and 25% survival, respectively, and survivors had Ψstem <-6 MPa (i.e., desiccation-susceptible species). The desiccation-avoiding species had lower relative water content (RWC) in all organs and tissues (root, stem, bark and xylem) in the drought treatment than in the reference plants (means 72.0-90.4% vs 86.9-97.9%), but the survivors of the desiccation-susceptible C. rufescens had much lower RWC in the drought treatment (44.5-72.1%). Among the reference plants, the desiccation-avoiding species had lower tissue density, leaf-mass fraction and lateral-root surface area (LRA) than the desiccation-susceptible species. Additionally, C. platanifolia and C. odorata had reduced LRA in the drought treatment, which may slow water loss into dry soil. Together, these results suggest that the ability to regulate Ψstem during extreme drought is associated with functional traits that favor retention of stored water and that safety margins during seasonal drought poorly predict survival during extreme drought. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Long-Term Post-Stroke Changes Include Myelin Loss, Specific Deficits in Sensory and Motor Behaviors and Complex Cognitive Impairment Detected Using Active Place Avoidance

    PubMed Central

    Li, Jie; Ooi, Evelyn; Bloom, Jonathan; Poon, Carrie; Lax, Daniel; Rosenbaum, Daniel M.; Barone, Frank C.

    2013-01-01

    Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO) or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1) sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG), hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001), sensory (p<0.001), beam balance performance (p<0.01) and hindlimb placement behavior (p<0.01). tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05) but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining). No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01) in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and can be important for cognitive behavioral control necessary for complex APA learning. PMID:23505432

  4. Flexible digestion strategies and trace metal assimilation in marine bivalves

    USGS Publications Warehouse

    Decho, Alan W.; Luoma, Samuel N.

    1996-01-01

    Pulse-chase experiments show that two marine bivalves take optimal advantage of different types of particulate food by varying food retention time in a flexible two-phase digestive system. For example, carbon is efficiently assimilated from bacteria by subjecting nearly all the ingested bacteria to prolonged digestion. Prolonging digestion also enhances assimilation of metals, many of which are toxic in minute quantities if they are biologically available. Detritus-feeding aquatic organisms have always lived in environments naturally rich in particle-reactive metals. We suggest that avoiding excess assimilation of metals could be a factor in the evolution of digestion strategies. We tested that suggestion by studying digestion of particles containing different Cr concentrations. We show that bivalves are capable of modifying the digestive processing of food to reduce exposure to high, biologically available, Cr concentrations. The evolution of a mechanism in some species to avoid high concentrations of metals in food could influence how effects of modern metal pollution are manifested in marine ecosystems.

  5. Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

    PubMed

    Brogden, Nicole K; Brogden, Kim A

    2011-09-01

    The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent promising therapeutic agents against bacterial and fungal pathogens. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or 'targeted' antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  6. Drosophila serpin 4 functions as a neuroserpin-like inhibitor of subtilisin-like proprotein convertases.

    PubMed

    Osterwalder, Thomas; Kuhnen, Angela; Leiserson, William M; Kim, You-Seung; Keshishian, Haig

    2004-06-16

    The proteolytic processing of neuropeptide precursors is believed to be regulated by serine proteinase inhibitors, or serpins. Here we describe the molecular cloning and functional expression of a novel member of the serpin family, Serine protease inhibitor 4 (Spn4), that we propose is involved in the regulation of peptide maturation in Drosophila. The Spn4 gene encodes at least two different serpin proteins, generated by alternate splicing of the last coding exon. The closest vertebrate homolog to Spn4 is neuroserpin. Like neuroserpin, one of the Spn4 proteins (Spn4.1) features a unique C-terminal extension, reminiscent of an endoplasmic reticulum (ER) retention signal; however, Spn4.1 and neuroserpin have divergent reactive site loops, with Spn4.1 showing a generic recognition site for furin/SPC1, the founding member of the intracellularly active family of subtilisin-like proprotein convertases (SPCs). In vitro, Spn4.1 forms SDS-stable complexes with the SPC furin and directly inhibits it. When Spn4.1 is overexpressed in specific peptidergic cells of Drosophila larvae, the animals exhibit a phenotype consistent with disrupted neuropeptide processing. This observation, together with the unique combination of an ER-retention signal, a target sequence for SPCs in the reactive site loop, and the in vitro inhibitory activity against furin, strongly suggests that Spn4.1 is an intracellular regulator of SPCs.

  7. Algal evolution in relation to atmospheric CO2: carboxylases, carbon-concentrating mechanisms and carbon oxidation cycles

    PubMed Central

    Raven, John A.; Giordano, Mario; Beardall, John; Maberly, Stephen C.

    2012-01-01

    Oxygenic photosynthesis evolved at least 2.4 Ga; all oxygenic organisms use the ribulose bisphosphate carboxylase-oxygenase (Rubisco)–photosynthetic carbon reduction cycle (PCRC) rather than one of the five other known pathways of autotrophic CO2 assimilation. The high CO2 and (initially) O2-free conditions permitted the use of a Rubisco with a high maximum specific reaction rate. As CO2 decreased and O2 increased, Rubisco oxygenase activity increased and 2-phosphoglycolate was produced, with the evolution of pathways recycling this inhibitory product to sugar phosphates. Changed atmospheric composition also selected for Rubiscos with higher CO2 affinity and CO2/O2 selectivity correlated with decreased CO2-saturated catalytic capacity and/or for CO2-concentrating mechanisms (CCMs). These changes increase the energy, nitrogen, phosphorus, iron, zinc and manganese cost of producing and operating Rubisco–PCRC, while biosphere oxygenation decreased the availability of nitrogen, phosphorus and iron. The majority of algae today have CCMs; the timing of their origins is unclear. If CCMs evolved in a low-CO2 episode followed by one or more lengthy high-CO2 episodes, CCM retention could involve a combination of environmental factors known to favour CCM retention in extant organisms that also occur in a warmer high-CO2 ocean. More investigations, including studies of genetic adaptation, are needed. PMID:22232762

  8. Mouse SLLP1, a sperm lysozyme-like protein involved in sperm-egg binding and fertilization.

    PubMed

    Herrero, María Belén; Mandal, Arabinda; Digilio, Laura C; Coonrod, Scott A; Maier, Bernhard; Herr, John C

    2005-08-01

    This study demonstrates the retention of mouse sperm lysozyme-like protein (mSLLP1) in the equatorial segment of spermatozoa following the acrosome reaction and a role for mSLLP1 in sperm-egg binding and fertilization. Treatment of cumulus intact oocytes with either recmSLLP1 or its antiserum resulted in a significant (P < or = 0.05) inhibition of fertilization. Co-incubation of zona-free mouse oocytes with capacitated mouse spermatozoa in the presence of varying concentrations of anti-recmSLLP1 serum or recmSLLP1 also inhibited sperm-oolemma binding. A complete inhibition of binding and fusion of spermatozoa to the oocyte occurred at 12.5 muM concentration of recmSLLP1, while conventional chicken and human lysozymes did not block sperm-egg binding. mSLLP1 showed receptor sites in the perivitelline space as well as on the microvillar region of the egg plasma membrane. The retention of mSLLP1 in the equatorial segment of acrosome-reacted sperm, the inhibitory effects of both recmSLLP1 and antibodies to SLLP1 on in vitro fertilization with both cumulus intact and zona-free eggs, and the definition of complementary SLLP1-binding sites on the egg plasma membrane together support the hypothesis that a c lysozyme-like protein is involved in the binding of spermatozoa to the egg plasma membrane during fertilization.

  9. Inhibition to excitation ratio regulates visual system responses and behavior in vivo.

    PubMed

    Shen, Wanhua; McKeown, Caroline R; Demas, James A; Cline, Hollis T

    2011-11-01

    The balance of inhibitory to excitatory (I/E) synaptic inputs is thought to control information processing and behavioral output of the central nervous system. We sought to test the effects of the decreased or increased I/E ratio on visual circuit function and visually guided behavior in Xenopus tadpoles. We selectively decreased inhibitory synaptic transmission in optic tectal neurons by knocking down the γ2 subunit of the GABA(A) receptors (GABA(A)R) using antisense morpholino oligonucleotides or by expressing a peptide corresponding to an intracellular loop of the γ2 subunit, called ICL, which interferes with anchoring GABA(A)R at synapses. Recordings of miniature inhibitory postsynaptic currents (mIPSCs) and miniature excitatory PSCs (mEPSCs) showed that these treatments decreased the frequency of mIPSCs compared with control tectal neurons without affecting mEPSC frequency, resulting in an ∼50% decrease in the ratio of I/E synaptic input. ICL expression and γ2-subunit knockdown also decreased the ratio of optic nerve-evoked synaptic I/E responses. We recorded visually evoked responses from optic tectal neurons, in which the synaptic I/E ratio was decreased. Decreasing the synaptic I/E ratio in tectal neurons increased the variance of first spike latency in response to full-field visual stimulation, increased recurrent activity in the tectal circuit, enlarged spatial receptive fields, and lengthened the temporal integration window. We used the benzodiazepine, diazepam (DZ), to increase inhibitory synaptic activity. DZ increased optic nerve-evoked inhibitory transmission but did not affect evoked excitatory currents, resulting in an increase in the I/E ratio of ∼30%. Increasing the I/E ratio with DZ decreased the variance of first spike latency, decreased spatial receptive field size, and lengthened temporal receptive fields. Sequential recordings of spikes and excitatory and inhibitory synaptic inputs to the same visual stimuli demonstrated that decreasing or increasing the I/E ratio disrupted input/output relations. We assessed the effect of an altered I/E ratio on a visually guided behavior that requires the optic tectum. Increasing and decreasing I/E in tectal neurons blocked the tectally mediated visual avoidance behavior. Because ICL expression, γ2-subunit knockdown, and DZ did not directly affect excitatory synaptic transmission, we interpret the results of our study as evidence that partially decreasing or increasing the ratio of I/E disrupts several measures of visual system information processing and visually guided behavior in an intact vertebrate.

  10. Open field exposure facilitates recovery from an aversive emotional event: Involvement of adrenergic and cholinergic transmitter systems.

    PubMed

    Psyrdellis, Mariana; Pautassi, Ricardo Marcos; Justel, Nadia

    2016-10-28

    Successive negative contrast (SNC) is an incentive relativity procedure that has been widely used to model emotional reactivity in rodents. The reward downshift experienced during SNC is thought to result in frustration. The exploration of a novel open field (OF), a complex situation involving stress induction and novelty detection, can enhance or block the acquisition of associative and non-associative memories. Previous experiments found a modulatory effect of OF, applied before downshift trials, on SNC. This schedule, however, can affect retention performance by influencing attentional, motivational, motor or sensory-perceptual mechanisms at training or retention testing. The use of post-training OF exposure avoids these confounds. This work assessed the effect of OF exposure after the acquisition of the downshifted memory, with the goal of targeting the consolidation of this mnemonic trace. We also investigated the involvement of the cholinergic and adrenergic systems in this phenomenon. The results indicated that OF facilitates recovery from reward loss and that both transmitter systems, cholinergic and adrenergic, play a role in this effect of OF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. On the use of ionic liquids as mobile phase additives in high-performance liquid chromatography. A review.

    PubMed

    García-Alvarez-Coque, M C; Ruiz-Angel, M J; Berthod, A; Carda-Broch, S

    2015-07-09

    The popularity of ionic liquids (ILs) has grown during the last decades in several analytical separation techniques. Consequently, the number of reports devoted to the applications of ILs is still increasing. This review is focused on the use of ILs (mainly imidazolium-based associated to chloride and tetrafluoroborate) as mobile phase additives in high-performance liquid chromatography (HPLC). In this approach, ILs just function as salts, but keep several kinds of intermolecular interactions, which are useful for chromatographic separations. Both cation and anion can be adsorbed on the stationary phase, creating a bilayer. This gives rise to hydrophobic, electrostatic and other specific interactions with the stationary phase and solutes, which modify the retention behaviour and peak shape. This review updates the advances in this field, with emphasis on topics not always deeply considered in the literature, such as the mechanisms of retention, the estimation of the suppressing potency of silanols, modelling and optimisation of the chromatographic performance, and the comparison with other additives traditionally used to avoid the silanol problem. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Breakage of internal maxillary distractor: considerable complication of maxillary distraction osteogenesis.

    PubMed

    Aikawa, Tomonao; Iida, Seiji; Isomura, Emiko T; Namikawa, Mari; Matsuoka, Yudai; Yamada, Chiaki; Yamamoto, Taku; Takigawa, Yoko

    2008-07-01

    Maxillary distraction osteogenesis using intraoral distractors is now one of the standard treatments of maxillary retrusion. This report shows 2 cases of breakage of this internal maxillary distractor in patients with cleft lip and palate; one was observed during the distraction period and the other was during the retention period. The first case required a rotational movement of the distraction segment, and this movement caused the laterally dislocation of the posterior part of the distractor, where the distractor suffered some mechanical forces by mouth opening. In the latter case, breakage of distractor was observed on the radiographs taken 3 months after distraction and this complication may have been caused by mechanical force by occlusion and mastication. Both breakages were found at the joint of the anchorage plate and the extension rod, which has some flexibility for adjusting the plate to the bone surface. Therefore, surgeons should pay special attention for this mechanical weak area in this distractor not only during the advancement period, but also during the retention period and should avoid unnecessary frequent bending for adopting the bone surface, which directly weakens the joint.

  13. Barriers and Facilitators to Engagement and Retention in Care among Transgender Women Living with Human Immunodeficiency Virus

    PubMed Central

    Sevelius, Jae M.; Patouhas, Enzo; Keatley, JoAnne G.; Johnson, Mallory O.

    2014-01-01

    Background Transgender women have 49 times the odds of human immunodeficiency virus (HIV) infection compared to other groups, yet they are disproportionately underserved by current treatment efforts. Purpose To examine culturally unique barriers and facilitators to engagement and retention in HIV care and strengthen efforts to mitigate health disparities, guided by the Models of Gender Affirmation and Health Care Empowerment. Methods Through 20 interviews and 5 focus groups (n=38), transgender women living with HIV discussed their experiences and life contexts of engagement in and adherence to HIV care and treatment. Results Our participants faced substantial challenges to adhering to HIV care and treatment, including avoidance of healthcare due to stigma and past negative experiences, prioritization of hormone therapy, and concerns about adverse interactions between antiretroviral treatment for HIV and hormone therapy. Receiving culturally competent, transgender-sensitive healthcare was a powerful facilitator of healthcare empowerment. Conclusions Recommendations are offered to inform intervention research and guide providers, emphasizing gender affirming HIV care that integrates transition-related healthcare needs. PMID:24317955

  14. [Indication for antimycotic therapy for tracheobronchial candidosis under artificial ventilation].

    PubMed

    Grossherr, M; Sedemund-Adib, Beate; Klotz, K-F

    2005-01-01

    Tracheobronchial candidosis is an impetuous complication in intensive care medicine. This article presents a concept to compare diagnostic procedure, Candida species and resistant species of different intensive care units with each other. This concept should encourage bench marking between similar intensive care units. The report and retrospective analysis of the intensive care course offer the opportunity to reflect own decisions and to adjust them to the current therapy strategies. Both procedures should improve the antimycotic therapy for intensive care units and should avoid the occurrence of resistant species. Candida species are often detected in the respiratory system of ventilated patients in intensive care, but this alone is no indication for antimycotic therapy. A strict retention is recommended, but this retention is diminished by an unclear infection, critical situation of the patient in the case of multiple organ failure, additional infection and long term ventilation. A therapy strategy for individual situations should be established and a close diagnostic procedure should be performed. A positive blood culture or detection of Candida species in two or more diagnostic materials indicate an early antimycotic therapy.

  15. An Overview On Various Approaches And Recent Patents On Gastroretentive Drug Delivery Systems.

    PubMed

    Kumar, Manoj; Kaushik, Deepak

    2018-03-08

    Drugs having absorption window in the stomach or upper small intestine has restricted bioavailability with conventional dosage forms. The gastric residence time of these dosage forms is usually short and they do not show drug release for prolonged period of time. To avoid these problems and to enhance the bioavailability and gastric retention time of these drugs, controlled drug delivery systems with prolonged gastric retention time are currently being developed. This review highlights the various pharmaceutical approaches for gastroretention such as floating drug delivery systems, mucoadhesive systems, high density systems, expandable and swelling systems, superporous hydrogels systems, magnetic systems, ion exchange resin system and recent patents filed or granted for these approaches. Recently some patents are also reported where a combination of various approaches are being employed to achieve very effective gastroretention. The various patent search sites were used to collect and analyze the information on gastroretentive drug delivery systems. The present study provides valuable information, advantages, limitations and future outlook of various gastroretentive drug delivery systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Sleep and memory. I: The influence of different sleep stages on memory.

    PubMed

    Rotenberg, V S

    1992-01-01

    A new approach to the sleep stages role in memory is discussed in the context of the two opposite patterns of behavior-search activity and renunciation of search. Search activity is activity designed to change the situation (or the subjects attitudes to it) in the absence of a definite forecast of the results of such activity, but with the constant consideration of these results at all stages of activity. Search activity increases general adaptability and body resistance while renunciation of search decreases adaptability and requires REM sleep for its compensation. Unprepared learning, which is often accompanied by failures on the first steps of learning, is suggested to produce renunciation of search, which decreases learning ability, suppress retention, and increase REM sleep requirement. A prolonged REM sleep deprivation before training causes learned helplessness and disturbs the learning process, while short REM sleep deprivation cause the "rebound" of the compensatory search activity that interferes with passive avoidance. REM sleep deprivation performed after a training session can increase distress caused by a training procedure, with the subsequent negative outcome on retention.

  17. Impact of cercal air currents on singing motor pattern generation in the cricket (Gryllus bimaculatus DeGeer)

    PubMed Central

    2015-01-01

    The cercal system of crickets detects low-frequency air currents produced by approaching predators and self-generated air currents during singing, which may provide sensory feedback to the singing motor network. We analyzed the effect of cercal stimulation on singing motor pattern generation to reveal the response of a singing interneuron to predator-like signals and to elucidate the possible role of self-generated air currents during singing. In fictive singing males, we recorded an interneuron of the singing network while applying air currents to the cerci; additionally, we analyzed the effect of abolishing the cercal system in freely singing males. In fictively singing crickets, the effect of short air stimuli is either to terminate prematurely or to lengthen the interchirp interval, depending on their phase in the chirp cycle. Within our stimulation paradigm, air stimuli of different velocities and durations always elicited an inhibitory postsynaptic potential in the singing interneuron. Current injection in the singing interneuron elicited singing motor activity, even during the air current-evoked inhibitory input from the cercal pathway. The disruptive effects of air stimuli on the fictive singing pattern and the inhibitory response of the singing interneuron point toward the cercal system being involved in initiating avoidance responses in singing crickets, according to the established role of cerci in a predator escape pathway. After abolishing the activity of the cercal system, the timing of natural singing activity was not significantly altered. Our study provides no evidence that self-generated cercal sensory activity has a feedback function for singing motor pattern generation. PMID:26334014

  18. Effect of enterocin AS-48 in combination with biocides on planktonic and sessile Listeria monocytogenes.

    PubMed

    Gómez, Natacha Caballero; Abriouel, Hikmate; Grande, M A José; Pulido, Rubén Pérez; Gálvez, Antonio

    2012-05-01

    Enterocin AS-48 was tested on a cocktail of Listeria monocytogenes strains in planktonic and sessile states, singly or in combination with biocides benzalkonium chloride, cetrimide, hexadecylpyridinium chloride, didecyldimethylammonium bromide, triclosan, poly-(hexamethylen guanidinium) hydrochloride, chlorhexidine, hexachlorophene, and the commercial sanitizers P3 oxonia and P3 topax 66. Combinations of sub-inhibitory bacteriocin concentrations and biocide concentrations 4 to 10-fold lower than their minimum inhibitory concentrations (MIC) completely inhibited growth of the planktonic listeriae. Inactivation of Listeria in biofilms formed on polystyrene microtiter plates required concentrations of enterocin AS-48 greater than 50 μg/ml, and biocide concentrations ten to 100-fold higher. In combination with enterocin AS-48 (25 or 50 μg/ml), microbial inactivation increased remarkably for all biocides except P3 oxonia and P3 topax 66 solutions. Polystyrene microtiter plates conditioned with enterocin solutions (0.5-25 μg/ml) decreased the adherence and biofilm formation of the L. monocytogenes cell cocktail, avoiding biofilm formation for at least 24 h at a bacteriocin concentration of 25 μg/ml. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Neuroprotective Activities of Saffron and Crocin.

    PubMed

    Soeda, Shinji; Aritake, Kosuke; Urade, Yoshihiro; Sato, Hiroshi; Shoyama, Yukihiro

    2016-01-01

    We first considered that saffron is really safety food because it has a long-use history. The neuroprotective activities of saffron and its major constituent, crocin, are separately discussed in vitro and in vivo. We reviewed the inhibitory activities of crocin against PC-12 cell apoptosis. The oxidative stress decreased the cellular levels of glutathione (GSH) which is an inhibitor of neutral sphingomyelinase (N-SMase). Therefore, the level of GSH was assayed by the addition of crocin resulted in the activation of glutathione reductase (GR). It became evident that crocin treatment prevents the N-SMase activation resulting in the decrease of ceramide release. From these evidences we summarized the role of crocin for neuronal cell death. We used the ethanol-blocking assay system for learning and memory activities. The effect of saffron and crocin on improving ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks has been clear. Further, we did make clear that saffron and crocin prevent the inhibitory effect of ethanol on long-term potentiation (LTP) in the dentate gyrus. Finally we found that 100 mg/kg of crocin gave non-rapid eye movement sleep (non-REM sleep) although mice were started to be active during night time.

  20. Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of fragile X syndrome.

    PubMed

    Yuskaitis, Christopher J; Mines, Marjelo A; King, Margaret K; Sweatt, J David; Miller, Courtney A; Jope, Richard S

    2010-02-15

    Fragile X syndrome (FXS), the most common form of inherited mental retardation and a genetic cause of autism, results from mutated fragile X mental retardation-1 (Fmr1). This study examined the effects on glycogen synthase kinase-3 (GSK3) of treatment with a metabotropic glutamate receptor (mGluR) antagonist, MPEP, and the GSK3 inhibitor, lithium, in C57Bl/6 Fmr1 knockout mice. Increased mGluR signaling may contribute to the pathology of FXS, and the mGluR5 antagonist MPEP increased inhibitory serine-phosphorylation of brain GSK3 selectively in Fmr1 knockout mice but not in wild-type mice. Inhibitory serine-phosphorylation of GSK3 was lower in Fmr1 knockout, than wild-type, mouse brain regions and was increased by acute or chronic lithium treatment, which also increased hippocampal brain-derived neurotrophic factor levels. Fmr1 knockout mice displayed alterations in open-field activity, elevated plus-maze, and passive avoidance, and these differences were ameliorated by chronic lithium treatment. These findings support the hypothesis that impaired inhibition of GSK3 contributes to the pathogenesis of FXS and support GSK3 as a potential therapeutic target.

  1. Cancer control and prevention: nutrition and epigenetics.

    PubMed

    Verma, Mukesh

    2013-07-01

    To evaluate recent developments in nutritional epigenomics and related challenges, opportunities, and implications for cancer control and prevention. Cancer is one of the leading causes of death worldwide, and understanding the factors that contribute to cancer development may facilitate the development of strategies for cancer prevention and control. Cancer development involves genetic and epigenetic alterations. Genetic marks are permanent, whereas epigenetic marks are dynamic, change with age, and are influenced by the external environment. Thus, epigenetics provides a link between the environment, diet, and cancer development. Proper food selection is imperative for better health and to avoid cancer and other diseases. Nutrients either contribute directly to cancer prevention or support the repair of genomic and epigenomic damage caused by exposure to cancer-causing agents such as toxins, free radicals, radiation, and infectious agents. Nutritional epigenomics provides an opportunity for cancer prevention because selected nutrients have the potential to reverse cancer-associated epigenetic marks in different tumor types. A number of natural foods and their bioactive components have been shown to have methylation-inhibitory and deacetylation-inhibitory properties. Natural foods and bioactive food components have characteristics and functions that are similar to epigenetic inhibitors and therefore have potential in cancer control and prevention.

  2. PubMed

    Galaine, Jeanne; Godet, Yann; Adotévi, Olivier

    2016-11-01

    T cells activation is a finely regulated process to establish an effective anti-infectious or antitumor immune response while avoiding harmful autoimmune reactions. Although T cells are considered to be the main protagonists of the antitumor immune response, they act in interaction with other immune cells. The meeting of naive T cells with dendritic cells induces their differentiation into effector cells following the recognition of the peptide-MHC complex by the T cell receptor. The interaction of costimulatory molecules present on the surface of T cells with their ligand (s) expressed by mature dendritic cells contribute to the optimal T cell activation and to the formation of the immunological synapse. Conversely, engagement of inhibitory receptors expressed by T cells induces a negative feedback involved in the T cells homeostasis but also in the tumor escape from the immune system. The integration of stimulatory signals contributes to the proliferation, the survival and the differentiation of T cells whereas the inhibitory signals permit their regulation. The better understanding of T cell activation mechanisms has led to the development of therapeutic strategies aimed at stimulating the antitumor immune response or alleviating the immunosuppression. © 2016 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.

  3. The PSI Artist Project: Aerosol Retention and Accident Management Issues Following a Steam Generator Tube Rupture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guntay, Salih; Dehbi, Abdel; Suckow, Detlef

    2002-07-01

    Steam generator tube rupture (SGTR) incidents, such as those, which occurred in various operating pressurized, water reactors in the past, are serious operational concerns and remain among the most risk-dominant events. Although considerable efforts have been spent to understand tube degradation processes, develop improved modes of operation, and take preventative and corrective measures, SGTR incidents cannot be completely ruled out. Under certain conditions, high releases of radionuclides to the environment are possible during design basis accidents (DBA) and severe accidents. The severe accident codes' models for aerosol retention in the secondary side of a steam generator (SG) have not beenmore » assessed against any experimental data, which means that the uncertainties in the source term following an un-isolated SGTR concurrent with a severe accident are not currently quantified. The accident management (AM) procedures aim at avoiding or minimizing the release of fission products from the SG. The enhanced retention of activity within the SG defines the effectiveness of the accident management actions for the specific hardware characteristics and accident conditions of concern. A sound database on aerosol retention due to natural processes in the SG is not available, nor is an assessment of the effect of management actions on these processes. Hence, the effectiveness of the AM in SGTR events is not presently known. To help reduce uncertainties relating to SGTR issues, an experimental project, ARTIST (Aerosol Trapping In a Steam generator), has been initiated at the Paul Scherrer Institut to address aerosol and droplet retention in the various parts of the SG. The test section is comprised of a scaled-down tube bundle, a full-size separator and a full-size dryer unit. The project will study phenomena at the separate effect and integral levels and address AM issues in seven distinct phases: Aerosol retention in 1) the broken tube under dry secondary side conditions, 2) the near field close to break under dry conditions, 3) the bundle far-field under dry conditions, 4) the separator and dryer under dry conditions, 5) the bundle section under wet conditions, 6) droplet retention in the separator and dryer sections and 7) the overall SG (integral tests). Prototypical test parameters are selected to cover the range of conditions expected in severe accident as well as DBA scenarios. This paper summarizes the relevant issues and introduces the ARTIST facility and the provisional test program which will run between 2003 and 2007. (authors)« less

  4. Inhibition of long-term memory formation by anti-ependymin antisera after active shock-avoidance learning in goldfish.

    PubMed

    Piront, M L; Schmidt, R

    1988-02-23

    Ependymins are acidic glycoprotein constituents of goldfish brain cytoplasm and extracellular fluid which are known to participate in biochemical reactions of long-term memory formation. In earlier experiments, anti-ependymin antisera were found to cause amnesia when injected into goldfish brain ventricles after the acquisition of a vestibulomotoric training task. To investigate whether they also inhibit memory consolidation after other learning events the anti-ependymin antisera were injected after an active shock-avoidance learning paradigm, as follows: goldfish were trained in a shuttle-box to cross a barrier in order to avoid electric shocks (unconditioned stimulus) applied shortly after a light signal (conditioned stimulus). Anti-ependymin antisera blocked retention of the learned avoidance when injected 0.5, 4.5 or 24 h after acquisition of the new behavior. They had no effect, however, when injected 72 h after learning. Apparently, long-term memory was already consolidated at this point. Antisera injected 0.5 or 72 h prior to training, also did not influence learning or memory. Thirteen percent of the goldfish fled the light stimulus spontaneously. These fish therefore did not experience the unconditioned stimulus and thus were unable to learn the task. When they were treated with the anti-ependymin antisera and tested 3 days later, the spontaneous escape reaction was not affected (active control group). The ability of anti-ependymin antisera to inhibit memory consolidation and their efficacy after administration at specific time intervals are very similar for the active shock-avoidance learning and for the vestibulomotoric training. We conclude that ependymins are not task-specific, but serve a general function in biochemical reactions essential for long-term memory formation.

  5. Cardamom (Elettaria cardamomum) perinatal exposure effects on the development, behavior and biochemical parameters in mice offspring.

    PubMed

    Abu-Taweel, Gasem Mohammad

    2018-01-01

    Cardamom is a strong antioxidant plant, so it is called the queen of spices. In the present study, we explored the potentials of cardamom on developmental, learning ability and biochemical parameters of mice offspring. Thirty pregnant mice were allocated to three groups of ten animals in each. Groups Π and Ш received pilsbury's Diet containing 10 and 20% of cardamom (w/w) respectively, whereas Group I used as control. Cardomom was administered from the first day of pregnancy and was continued until post-natal day 15 (PD 15) and thereafter the mothers were switched to plain pilsbury's Diet. During the weaning period, three pups in each litter were color marked from the others, and were subjected to various tests (Physical assessment such body weight and eye opening and hair appearance; the neuromaturation of reflexes like righting, rotating, and cliff avoidance reflexes; learning ability and memory retention; estimation of monoamines neurotransmitters like dopamine and serotonin, non-enzymatic oxidative stress such as TBARS and GSH in forebrain at different ages of pups). The results indicated that the body weight gain was declining significantly. Hair appearance and eyes opening were delayed significantly. Righting, rotating, and cliff avoidance reflexes were delayed in treated animals. Exposure to cardamom led to enhance learning and memory retention as compared to control. Monoamines (DA, 5-HT) and GSH were elevated, whereas TBARS was inhibited significantly. In conclusion, perinatal cardamom exposure enhanced learning and memory as compared to control. Cardamom and its benefit compounds were transported via placenta or/and milk during lactation. Cardamom needs more researches to investigate its benefits on other kinds of behavior.

  6. Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory.

    PubMed

    Liu, Jian-Feng; Thorn, David A; Zhang, Yanan; Li, Jun-Xu

    2016-07-01

    As a modulator of dopaminergic system, trace amine-associated receptor 1 has been shown to play a critical role in regulating the rewarding properties of additive drugs. It has been demonstrated that activation of trace amine-associated receptor 1 decreased the abuse-related behaviors of cocaine in rats. However, the role of trace amine-associated receptor 1 in specific stages of cocaine reward memory is still unclear. Here, using a cocaine-induced conditioned place preference model, we tested the effects of a selective trace amine-associated receptor 1 agonist RO5166017 on the expression, reconsolidation, and extinction of cocaine reward memory. We found that RO5166017 inhibited the expression but not retention of cocaine-induced conditioned place preference. RO5166017 had no effect on the reconsolidation of cocaine reward memory. Pretreatment with RO5166017 before extinction hindered the formation of extinction long-term memory. RO5166017 did not affect the movement during the conditioned place preference test, indicating the inhibitory effect of RO5166017 on the expression of cocaine-induced conditioned place preference was not caused by locomotion inhibition. Using a cocaine i.v. self-administration model, we found that the combined trace amine-associated receptor 1 partial agonist RO5263397 with extinction had no effect on the following cue- and drug-induced reinstatement of cocaine-seeking behavior. Repeated administration of the trace amine-associated receptor 1 agonist during extinction showed a continually inhibitory effect on the expression of cocaine reward memory both in cocaine-induced conditioned place preference and cocaine self-administration models. Taken together, these results indicate that activation of trace amine-associated receptor 1 specifically inhibited the expression of cocaine reward memory. The inhibitory effect of trace amine-associated receptor 1 agonists on cocaine reward memory suggests that trace amine-associated receptor 1 agonists could be a promising agent to prevent cocaine relapse. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  7. Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.

    PubMed

    Rossetti, Tom; Banerjee, Somdeb; Kim, Chris; Leubner, Megan; Lamar, Casey; Gupta, Pooja; Lee, Bomsol; Neve, Rachael; Lisman, John

    2017-09-27

    The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The relationship between personality and sexual motivation: an investigation based on Cloninger's model in nonclinical Italian subjects.

    PubMed

    Micò, Umberto; Scimeca, Giuseppe; Bruno, Antonio; Pandolfo, Gianluca; Romeo, Vincenzo M; Mallamace, Domenico; Zoccali, Rocco; Muscatello, Maria R A

    2013-01-01

    The aim of this study was to investigate the relationship between personality and sexual motivation according to Cloninger's psychobiological model of the personality. Three hundred and ten volunteers recruited among the students of the University of Messina, Italy, participated in the study. All subjects underwent a psychometric examination with the following instruments: Temperament and Character Inventory (TCI) and Sex and the Average Woman (or Man; SAWM). The best negative predictor of Sexual Excitement and Satisfaction was the temperamental dimension Harm Avoidance; as it regards character dimensions, Cooperativeness was the best negative predictor of Sexual Excitement, while Self-Directedness was the best positive predictor of Sexual Satisfaction. Overall, inhibitory aspects of the personality have deeper effects on sexual motivation than excitatory ones. The results of this research suggest the importance of studying the relationship between personality and sexual behavior. An integrative psychobiological approach to the study of sexual excitement and satisfaction may give a fundamental contribution to the assessment and psychological treatment of predisposing personality factors (like avoidant tendencies) involved in the development and persistence of sexual dysfunction.

  9. Da-Chaihu-Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this.

    PubMed

    He, Ju-Xiu; Ohno, Kenji; Tang, Jun; Hattori, Masao; Tani, Tadato; Akao, Teruaki

    2014-11-01

    To investigate the influence of co-administrated Da-Chaihu-Tang (DCT; a traditional Chinese formulation) on the pharmacokinetics of nifedipine, as well as the safe optimal dosing interval to avoid the adverse interactions. A single dose of DCT was administered with nifedipine simultaneously, 2 h before, 30 min before or 30 min after nifedipine administration. Pharmacokinetics of nifedipine with or without DCT were compared. The influences of DCT on nifedipine intestinal mucosal and hepatic metabolism were studied by using rat in-vitro everted jejunal sac model and hepatic microsomes. A simultaneous co-administration of DCT significantly increased the area under concentration-time curve from time zero to infinity (AUC0-inf ) of nifedipine. In-vitro mechanism investigations revealed that DCT inhibited both the intestinal and the hepatic metabolism of nifedipine. Further study on the optimal dosing interval for nifedipine and DCT revealed that administration of DCT 30 min before or after nifedipine did not significantly change the AUC of nifedipine. The bioavailability of nifedipine is significantly increased by a simultaneous oral co-administration of DCT. This increase is caused by the inhibitory effect of DCT on both the intestinal mucosal and the hepatic metabolism of nifedipine. The dose interval between DCT and nifedipine needs to be set for over 30 min to avoid such drug-drug interactions. © 2014 Royal Pharmaceutical Society.

  10. Generation of accurate peptide retention data for targeted and data independent quantitative LC-MS analysis: Chromatographic lessons in proteomics.

    PubMed

    Krokhin, Oleg V; Spicer, Vic

    2016-12-01

    The emergence of data-independent quantitative LC-MS/MS analysis protocols further highlights the importance of high-quality reproducible chromatographic procedures. Knowing, controlling and being able to predict the effect of multiple factors that alter peptide RP-HPLC separation selectivity is critical for successful data collection for the construction of ion libraries. Proteomic researchers have often regarded RP-HPLC as a "black box", while vast amount of research on peptide separation is readily available. In addition to obvious parameters, such as the type of ion-pairing modifier, stationary phase and column temperature, we describe the "mysterious" effects of gradient slope, column size and flow rate on peptide separation selectivity. Retention time variations due to these parameters are governed by the linear solvent strength (LSS) theory on a peptide level by the value of its slope S in the basic LSS equation-a parameter that can be accurately predicted. Thus, the application of shallower gradients, higher flow rates, or smaller columns will each increases the relative retention of peptides with higher S-values (long species with multiple positively charged groups). Simultaneous changes to these parameters that each drive shifts in separation selectivity in the same direction should be avoided. The unification of terminology represents another pressing issue in this field of applied proteomics that should be addressed to facilitate further progress. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Physical and antimicrobial properties of thyme oil emulsions stabilized by ovalbumin and gum arabic.

    PubMed

    Niu, Fuge; Pan, Weichun; Su, Yujie; Yang, Yanjun

    2016-12-01

    Natural biopolymer stabilized oil-in-water emulsions were formulated using ovalbumin (OVA), gum arabic (GA) solutions and their complexes. The influence of interfacial structure of emulsion (OVA-GA bilayer and OVA/GA complexes emulsions) on the physical properties and antimicrobial activity of thyme oil (TO) emulsion against Escherichia coli (E. coli) was evaluated. The results revealed that the two types of emulsions with different oil phase compositions remained stable during a long storage period. The oil phase composition had an appreciable influence on the mean particle diameter and retention of the TO emulsions. The stable emulsion showed a higher minimum inhibitory concentration (MIC), and the TO emulsions showed an improved long-term antimicrobial activity compared to the pure thyme oil, especially complexes emulsion at pH 4.0. These results provided useful information for developing protection and delivery systems for essential oil using biopolymer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Biostimulation and rainfall infiltration: influence on retention of biodiesel in residual clayey soil.

    PubMed

    Thomé, Antônio; Cecchin, Iziquiel; Reginatto, Cleomar; Colla, Luciane M; Reddy, Krishna R

    2017-04-01

    This study investigates the retention of biodiesel in residual clayey soil during biostimulation by nutrients (nitrogen, phosphorus, and potassium) under conditions of rainfall infiltration. Several column tests were conducted in a laboratory under different void ratios (1.14, 1.24, and 1.34), varying moisture contents (15, 25, and 35%), and in both the presence and absence of biostimulation. The volume of biodiesel (which was equivalent to the volume of voids in the soil) was placed atop the soil and allowed to percolate for a period of 15 days. The soil was subjected to different rainfall infiltration conditions (0.30 or 60 mm). The greatest reductions in residual contaminants occurred after 60 mm of rain simulation, at values of up to 74% less than in samples with the same conditions but no precipitation. However, the residual contamination decay rate was greater with 0-30 mm (0.29 g/mm) of precipitation than with 30-60 mm (0.075 g/mm). Statistical assessment revealed that increased moisture and the presence of nutrients were the factors with the most powerful effect on contaminant retention in the soil. The residual contaminant level was 21 g/kg at a moisture content of 15% and no precipitation, decreasing to 12 g/kg at 35% moisture and no precipitation. Accordingly, it is possible to conclude that biostimulation and rainfall infiltration conditions can decrease the retention of contaminants in soil and allow a greater leaching or spreading of the contamination. All of these phenomena are worthy of careful examination for the in situ bioremediation of organic contamination. • The higher moisture in the soil, due to a high initial moisture content and/or infiltration of rainfall, can reduce contaminant retention, • The use of biostimulation through the addition of nutrients to accelerate the biodegradation of toxic organic contaminants may induce inadvertent undesirable interactions between the soil and the contaminant. • When adopting biostimulation for bioremediation, the effects of rainfall should be addressed; ideally, it should be prevented from entering the affected site, in order to avoid increased contaminant leaching and potential spreading.

  13. Nootropic effect of meadowsweet (Filipendula vulgaris) extracts.

    PubMed

    Shilova, I V; Suslov, N I

    2015-03-01

    The effects of the extracts of the aboveground parts of Filipendula vulgaris Moench on the behavior and memory of mice after hypoxic injury and their physical performance in the open-field test were studied using the models of hypoxia in a sealed volume, conditioned passive avoidance response (CPAR), and forced swimming with a load. The extracts improved animal resistance to hypoxia, normalized orientation and exploration activities, promoted CPAR retention after hypoxic injury, and increased physical performance. Aqueous extract of meadowsweet had the most pronounced effect that corresponded to the effect of the reference drug piracetam. These effects were probably caused by modulation of hippocampal activity.

  14. An Alternate, Egg-Free Radiolabeled Meal Formulation for Gastric-Emptying Scintigraphy.

    PubMed

    Garrigue, Philippe; Bodin-Hullin, Aurore; Gonzalez, Sandra; Sala, Quentin; Guillet, Benjamin

    2017-07-01

    Tc-radiolabeled scrambled eggs (SEs) are most often used as the ingested solid phase for gastric-emptying scintigraphy, leading egg-reluctant patients to avoid the examination. We formulated and validated 2 egg-free alternate meals, in the absence of any commercialized formulation: chocolate mug cake (MC) and scrambled tofu (ST). Six healthy volunteers underwent gastric-emptying scintigraphy after ingesting Tc-radiolabeled MC, ST, or SE. Gastric retention indexes did not change significantly between formulations (% of overtime variation to SE: MC 7.75% ± 7.1%, ST 7.17% ± 5.8%; P = 0.6618, not statistically significant), suggesting MC and ST as interesting egg-free alternatives.

  15. Bio-assay guided isolation of α-glucosidase inhibitory constituents from Hibiscus mutabilis leaves.

    PubMed

    Kumar, Deepak; Kumar, Hemanth; Vedasiromoni, J R; Pal, Bikas C

    2012-01-01

    The increasing demand for natural-product-based medicines and health-care products for the management of diabetes encouraged investigation of this commonly available Indian plant. To establish the anti-diabetic (α-glucosidase inhibitory) activity of H. mutabilis leaf extract, isolate and identify the constituents responsible for the activity, and validate a HPLC method for quantification of the active constituents for standardisation of the extract. The methanolic extract of leaves was partitioned between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based on inhibition of α-glucosidase, allowed isolation and identification of the active components. The active components were quantified using RP-HPLC-DAD validated for linearity, limit of detection, limit of quantification, precision, accuracy and robustness for this plant extract and the partitioned fractions. Ferulic acid and caffeic acid were identified as the α-glucosidase inhibitors present in H. mutabilis. They were partitioned into an ethyl acetate fraction. The HPLC-DAD calibration curve showed good linearity (r² > 0.99). For the recovery studies the %RSD was less than 2%. The interday and intraday variations were found to be less than 4% RSD for retention time and response. The identification of α-glucosidase inhibition activity in H. mutabilis supports further investigations into the possible use of the plant for the management of diabetes. The HPLC method validated for these extracts will be useful in future research with the plant. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Inhibitory effect of cyanide on wastewater nitrification ...

    EPA Pesticide Factsheets

    The effect of CN- (CN-) on nitrification was examined with samples from nitrifying wastewater enrichments using two different approaches: by measuring substrate (ammonia) specific oxygen uptake rates (SOUR), and by using RT-qPCR to quantify the transcripts of functional genes involved in nitrification. The nitrifying bioreactor was operated as a continuous reactor with a 24 h hydraulic retention time. The samples were exposed in batch vessels to cyanide for a period of 12 h. The concentrations of CN- used in the batch assays were 0.03, 0.06, 0.1 and 1.0 mg/L. There was considerable decrease in SOUR with increasing dosages of CN-. A decrease of more than 50% in nitrification activity was observed at 0.1 mg/L CN-. Based on the RT-qPCR data, there was notable reduction in the transcript levels of amoA and hao for increasing CN- dosage, which corresponded well with the ammonia oxidation activity measured via SOUR. The inhibitory effect of cyanide may be attributed to the affinity of cyanide to bind ferric heme proteins, which disrupt protein structure and function. The correspondence between the relative expression of functional genes and SOUR shown in this study demonstrates the efficacy of RNA based function-specific assays for better understanding of the effect of toxic compounds on nitrification activity in wastewater. Nitrification is the first step of nitrogen removal is wastewater, and it is susceptible to inhibition by many industrial chemical. We looked at

  17. Failure to Find Ethanol-Induced Conditioned Taste Aversion in Honey Bees (Apis mellifera L.).

    PubMed

    Varnon, Christopher A; Dinges, Christopher W; Black, Timothy E; Wells, Harrington; Abramson, Charles I

    2018-04-24

    Conditioned taste aversion (CTA) learning is a highly specialized form of conditioning found across taxa that leads to avoidance of an initially neutral stimulus, such as taste or odor, that is associated with, but is not the cause of, a detrimental health condition. This study examines if honey bees (Apis mellifera L.) develop ethanol (EtOH)-induced CTA. Restrained bees were first administered a sucrose solution that was cinnamon scented, lavender scented, or unscented, and contained either 0, 2.5, 5, 10, or 20% EtOH. Then, 30 minutes later, we used a proboscis extension response (PER) conditioning procedure where the bees were taught to associate either cinnamon odor, lavender odor, or an air-puff with repeated sucrose feedings. For some bees, the odor of the previously consumed EtOH solution was the same as the odor associated with sucrose in the conditioning procedure. If bees are able to learn EtOH-induced CTA, they should show an immediate low level of response to odors previously associated with EtOH. We found that bees did not develop CTA despite the substantial inhibitory and aversive effects EtOH has on behavior. Instead, bees receiving a conditioning odor that was previously associated with EtOH showed an immediate high level of response. While this demonstrates bees are capable of one-trial learning common to CTA experiments, this high level of response is the opposite of what would occur if the bees developed a CTA. Responding on subsequent trials also showed a general inhibitory effect of EtOH. Finally, we found that consumption of cinnamon extract reduced the effects of EtOH. The honey bees' lack of learned avoidance to EtOH mirrors that seen in human alcoholism. These findings demonstrate the usefulness of honey bees as an insect model for EtOH consumption. Copyright © 2018 by the Research Society on Alcoholism.

  18. Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

    PubMed

    Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Ceretta, Renan A; Dominguini, Diogo; Ferrari, Pâmela; Gubert, Carolina; Jornada, Luciano K; Budni, Josiane; Kapczinski, Flávio; Quevedo, João

    2014-10-01

    Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis. © 2014 by the Society for Experimental Biology and Medicine.

  19. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    PubMed

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-11-01

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

  20. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze.

    PubMed

    Hatano, V Y; Torricelli, A S; Giassi, A C C; Coslope, L A; Viana, M B

    2012-03-01

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

  1. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

    PubMed Central

    Hatano, V.Y.; Torricelli, A.S.; Giassi, A.C.C.; Coslope, L.A.; Viana, M.B.

    2012-01-01

    Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer. PMID:22358424

  2. A novel interpretation of the Fractional Inhibitory Concentration Index: The case Origanum vulgare L. and Leptospermum scoparium J. R. et G. Forst essential oils against Staphylococcus aureus strains.

    PubMed

    Fratini, Filippo; Mancini, Simone; Turchi, Barbara; Friscia, Elisabetta; Pistelli, Luisa; Giusti, Giulia; Cerri, Domenico

    2017-01-01

    Origanum vulgare (oregano) and Leptospermum scoparium (manuka) were traditionally employed as natural remedies for infected wounds and skin injuries where Staphylococcus aureus is mainly involved. The first aim of this study was to investigate oregano and manuka essential oils (EOs) chemical compositions and evaluate their antibacterial activity (MIC, Minimum Inhibitory Concentration) against fourteen S. aureus wild strains. The second aim was to evaluate the antibacterial activities of oregano and manuka EOs mixed in different combination (FIC, Fractional Inhibitory Concentration) with an improved chequerboard technique. This allowed to avoid the usual uncertainty in the determination of MIC and FIC values and to obtain a more precise interpretation of FIC indexes (FICIs). Moreover, FICIs were discussed on the basis of a novel interpretation method to evaluate the synergistic/antagonistic effect of EOs mixtures. The most representative compounds in oregano EO were Carvacrol (65.93%), p-Cymene (9.33%) and γ-Terpinene (5.25%), while in manuka EO were Leptospermone (31.65%), cis-Calamenene (15.93%) and Flavesone (6.92%). EOs presented MIC values ranging from 1:2048 to 1:4096 v/v and FIC values ranging from 0.125 to 1. According to our interpretation, a synergistic effect (34.68%), a commutative effect (15.32%) and an indifferent effect (50.00%) and no antagonistic effect were observed. Conversely, according to two previously proposed FICI interpretation models, 1.80% synergistic effect could be observed and, respectively, 98.20% indifferent effect or 48.20% additive effect and 50.00% indifferent effect. As practical results, oregano and manuka EOs may be an effective alternative to chemotherapic drugs in staphylococcal infections and useful tools to enhance food security. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. PD-1 and cancer: molecular mechanisms and polymorphisms.

    PubMed

    Salmaninejad, Arash; Khoramshahi, Vahid; Azani, Alireza; Soltaninejad, Ehsan; Aslani, Saeed; Zamani, Mohammad Reza; Zal, Masoud; Nesaei, Abolfazl; Hosseini, Sayed Mostafa

    2018-02-01

    The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers. In particular, PD-1 over-expression influences tumor-specific T cell immunity in a cancer microenvironment. Blocking the PD-1/PD-1 ligand (PD-L1) pathway could potentially augment endogenous antitumor responses. Along these lines, the use of PD-1/PD-L1 inhibitors has been applied in clinical trials against diverse forms of cancer. It was believed that antibodies targeting PD-1/PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity by blocking inhibitory receptor-ligand interactions. However, in all cases, the host genetic status (as well as that of the tumor) is likely to have an impact on the expected outcomes. Various investigations have evaluated the association between PD-1 polymorphisms and the risk of various types of cancer. Frequently studied PD-1 polymorphisms, PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.9 (rs2227982), and PD-1 rs7421861, and their associations in the risk of susceptibility to different types of cancer are mentioned in this review, as are studies highlighting the significance of conducting genetic association studies in different ethnic populations.

  4. The effects of metallic engineered nanoparticles upon plant systems: An analytic examination of scientific evidence.

    PubMed

    Tolaymat, Thabet; Genaidy, Ash; Abdelraheem, Wael; Dionysiou, Dionysios; Andersen, Christian

    2017-02-01

    Recent evidence for the effects of metallic engineered nanoparticles (ENPs) on plants and plant systems was examined together with its implications for other constituents of the Society-Environment-Economy (SEE) system. In this study, we were particularly interested to determine whether or not metallic ENPs have both stimulatory and inhibitory effects upon plant performance. An emphasis was made to analyze the scientific evidence on investigations examining both types of effects in the same studies. Analysis of evidence demonstrated that metallic ENPs have both stimulatory and inhibitory effects mostly in well-controlled environments and soilless media. Nano zero-valent iron (nZVI) and Cu ENPs have potential for use as micronutrients for plant systems, keeping in mind the proper formulation at the right dose for each type of ENP. The concentration levels for the stimulatory effects of Cu ENPs are lower than for those for nZVI. Newer findings showed that extremely smaller concentrations of Au ENPs (smaller than those for nZVI and Cu ENPs) induce positive effects for plant growth, which is attributed to effects on secondary metabolites. Ag ENPs have demonstrated their usage as antimicrobial/pesticidal agents for plant protection; however, precautions should be taken to avoid higher concentrations not only for plant systems, but also, other constituents in the SEE. Further research is warranted to investigate the stimulatory and inhibitory effects of metallic ENPs in soil media in order to broaden the horizon of sustainable agriculture production in terms of higher and safer yields so as to meet the food requirements of human population. Copyright © 2016. Published by Elsevier B.V.

  5. Belief-desire reasoning as a process of selection.

    PubMed

    Leslie, Alan M; German, Tim P; Polizzi, Pamela

    2005-02-01

    Human learning may depend upon domain specialized mechanisms. A plausible example is rapid, early learning about the thoughts and feelings of other people. A major achievement in this domain, at about age four in the typically developing child, is the ability to solve problems in which the child attributes false beliefs to other people and predicts their actions. The main focus of theorizing has been why 3-year-olds fail, and only recently have there been any models of how success is achieved in false-belief tasks. Leslie and Polizzi (Inhibitory processing in the false-belief task: Two conjectures. Developmental Science, 1, 247-254, 1998) proposed two competing models of success, which are the focus of the current paper. The models assume that belief-desire reasoning is a process which selects a content for an agent's belief and an action for the agent's desire. In false belief tasks, the theory of mind mechanism (ToMM) provides plausible candidate belief contents, among which will be a 'true-belief.' A second process reviews these candidates and by default will select the true-belief content for attribution. To succeed in a false-belief task, the default content must be inhibited so that attention shifts to another candidate belief. In traditional false-belief tasks, the protagonist's desire is to approach an object. Here we make use of tasks in which the protagonist has a desire to avoid an object, about which she has a false-belief. Children find such tasks much more difficult than traditional tasks. Our models explain the additional difficulty by assuming that predicting action from an avoidance desire also requires an inhibition. The two processing models differ in the way that belief and desire inhibitory processes combine to achieve successful action prediction. In six experiments we obtain evidence favoring one model, in which parallel inhibitory processes cancel out, over the other model, in which serial inhibitions force attention to a previously inhibited location. These results are discussed in terms of a set of simple proposals for the modus operandi of a domain specific learning mechanism. The learning mechanism is in part modular--the ToMM--and in part penetrable--the Selection Processor (SP). We show how ToMM-SP can account both for competence and for successful and unsuccessful performance on a wide range of belief-desire tasks across the preschool period. Together, ToMM and SP attend to and learn about mental states.

  6. Cannabinoid facilitation of fear extinction memory recall in humans

    PubMed Central

    Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Abelson, James L.; Liberzon, Israel; Milad, Mohammed R.; Phan, K. Luan

    2012-01-01

    A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 hours prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 hours after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 hours after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. PMID:22796109

  7. Retention of community college students in online courses

    NASA Astrophysics Data System (ADS)

    Krajewski, Sarah

    The issue of attrition in online courses at higher learning institutions remains a high priority in the United States. A recent rapid growth of online courses at community colleges has been instigated by student demand, as they meet the time constraints many nontraditional community college students have as a result of the need to work and care for dependents. Failure in an online course can cause students to become frustrated with the college experience, financially burdened, or to even give up and leave college. Attrition could be avoided by proper guidance of who is best suited for online courses. This study examined factors related to retention (i.e., course completion) and success (i.e., receiving a C or better) in an online biology course at a community college in the Midwest by operationalizing student characteristics (age, race, gender), student skills (whether or not the student met the criteria to be placed in an AFP course), and external factors (Pell recipient, full/part time status, first term) from the persistence model developed by Rovai. Internal factors from this model were not included in this study. Both univariate analyses and multivariate logistic regression were used to analyze the variables. Results suggest that race and Pell recipient were both predictive of course completion on univariate analyses. However, multivariate analyses showed that age, race, academic load and first term were predictive of completion and Pell recipient was no longer predictive. The univariate results for the C or better showed that age, race, Pell recipient, academic load, and meeting AFP criteria were predictive of success. Multivariate analyses showed that only age, race, and Pell recipient were significant predictors of success. Both regression models explained very little (<15%) of the variability within the outcome variables of retention and success. Therefore, although significant predictors were identified for course completion and retention, there are still many factors that remain unaccounted for in both regression models. Further research into the operationalization of Rovai's model, including internal factors, to predict completion and success is necessary.

  8. Hypobaric Conditions and Retention of Dental Crowns Luted with Manually or Automixed Dental Cements.

    PubMed

    Kielbassa, Andrej M; Müller, Johannes A G

    2018-05-01

    There is only scant information on the influence of the hypobaric environment on luting agents and their efficacy on dental crown cementation. The objective of this study was to provide data on the retentive characters of two cements commonly used on implant abutment surfaces both under normal and under hypobaric conditions. There were 56 implant abutments supplied with CAD/CAM milled zirconia oxide crowns. 1) A zinc phosphate cement (ZP), and 2) a resin-modified glass ionomer cement (RMGI), each mixed either A) manually or B) by means of automix capsules, were used for cementation. The cemented crowns of the 4 × 2 subgroups were either kept on the ground or were transported in an aircraft at altitudes up to 13,730 m (45,045.9 ft; N = 28 each), thus being subjected to the pressure changes (80×) every aircrew member or frequent flyer is exposed to. All cemented crowns were stored in climatized boxes during the experimental phase. Hand-mixing of ZP resulted in a significant reduction of mean (± SD) retention forces (581.6 ± 204.5 N) when compared to the control group on the ground (828.4 ± 147.9 N). Automixed ZP (931.9 ± 134.4 N in flight; 996.0 ± 107.4 N on the ground) and RMGI subgroups (ranging from 581.0 N ± 114.3 N to 662.4 N ± 92.5 N) were not affected by hypobaric conditions. When treating patients frequently exposed to hypobaric environments, automixing of ZP would seem favorable, while manual mixing should be avoided. RMGI is considered suitable and is not influenced by hand-mixing or barometric pressure changes.Kielbassa AM, Müller JAG. Hypobaric conditions and retention of dental crowns luted with manually or automixed dental cements. Aerosp Med Hum Perform. 2018; 89(5):446-452.

  9. Trunk kinematics and fall risk of older adults: translating biomechanical results to the clinic.

    PubMed

    Grabiner, Mark D; Donovan, Stephanie; Bareither, Mary Lou; Marone, Jane R; Hamstra-Wright, Karrie; Gatts, Strawberry; Troy, Karen L

    2008-04-01

    This paper reviews some of our experiences over nearly 15 years of trying to determine modifiable factors that contribute to the high incidence of fall by older adults. As part of our approach, we have subjected healthy young and older adults to very large postural disturbances during locomotion, in the form of trips and slips, to which rapid compensatory responses have been necessary to avoid falling. For both trips and slips, the ability to limit trunk motion has consistently discriminated older adults who fall from both younger adults and older adults who have been able to avoid falling. We have shown that the ability to limit trunk motion can be rapidly acquired, or learned, by older adults as a result of task-specific training. The learned motor skill has demonstrated short-term retention and has been shown to effectively decrease fall-risk due to trips. Collectively, we believe the works strongly suggests that the traditional exercise-based fall-prevention and whole-body, task-specific training can synergize to reduce falls and fall-related injury in older adults.

  10. Safe percutaneous suprapubic catheterisation.

    PubMed

    Goyal, N K; Goel, A; Sankhwar, S N

    2012-11-01

    We describe our technique of percutaneous suprapubic catheter insertion with special reference to steps that help to avoid common complications of haematuria and catheter misplacement. The procedure is performed using a stainless steel reusable trocar under local infiltrative anaesthesia, usually at the bedside. After clinical confirmation of a full bladder, the trocar is advanced into the bladder through a skin incision. Once the bladder is entered, the obturator is removed and the assistant inserts a Foley catheter followed by rapid balloon inflation. Slight traction is applied to the catheter for about five minutes. Patients with previous lower abdominal surgery, an inadequately distended bladder or acute pelvic trauma do not undergo suprapubic catheterisation using this method. The procedure was performed in 72 men (mean age: 42.4 years, range: 18-78 years) with urinary retention with a palpable bladder. The average duration of the procedure was less than five minutes. No complications were noted in any of the patients. Trocar suprapubic catheter insertion is a safe and effective bedside procedure for emergency bladder drainage and can be performed by resident surgeons. The common complications associated with the procedure can be avoided with a few careful steps.

  11. The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats.

    PubMed

    Mora, S; Millán, R; Lungenstrass, H; Díaz-Véliz, G; Morán, J A; Herrera-Ruiz, M; Tortoriello, J

    2006-06-15

    Behavioral effects of a hydroalcoholic (60% ethanol) extract from the leaves of Salvia elegans Vahl (Lamiaceae) were studied in male Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Putative anxiolytic and antidepressant properties of Salvia elegans were studied in the elevated plus-maze test (EPM) and in the forced swimming test (FST), respectively. Deleterious effects of Salvia elegans on learning and memory were also studied by using active and passive avoidance paradigms. The results revealed that all doses (3.12, 12.5, 25 and 50 mg/kg) of the extract caused a significant decrease in total motility, locomotion, rearing and grooming behavior. Only the dose of 12.5 mg/kg increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg). In the FST, all doses of the extract induced a reduction of immobility, in a similar way to that of fluoxetine (10 mg/kg) and imipramine (12.5 mg/kg), along with a significant increase in the time spent in swimming behavior. Acquisition of active avoidance responses was disrupted by pre-treatment with the extract, but retention of a passive avoidance response was not significantly modified. These results suggest that some of the components of the hydroalcoholic extract of Salvia elegans have psychotropic properties, which deserve further investigation.

  12. A microtitre-based method for measuring the haem polymerization inhibitory activity (HPIA) of antimalarial drugs.

    PubMed

    Basilico, N; Pagani, E; Monti, D; Olliaro, P; Taramelli, D

    1998-07-01

    The malaria parasite metabolizes haemoglobin and detoxifies the resulting haem by polymerizing it to form haemozoin (malaria pigment). A polymer identical to haemozoin, beta-haematin, can be obtained in vitro from haematin at acidic pH. Quinoline-containing anti-malarials (e.g. chloroquine) inhibit the formation of either polymer. Haem polymerization is an essential and unique pharmacological target. To identify molecules with haem polymerization inhibitory activity (HPIA) and quantify their potency, we developed a simple, inexpensive, quantitative in-vitro spectrophotometric microassay of haem polymerization. The assay uses 96-well U-bottomed polystyrene microplates and requires 24 h and a microplate reader. The relative amounts of polymerized and unpolymerized haematin are determined, based on solubility in DMSO, by measuring absorbance at 405 nm in the presence of test compounds as compared with untreated controls. The final product (a solid precipitate of polymerized haematin) was validated using infrared spectroscopy and the assay proved reproducible; in this assay, activity could be partly predicted based on the compound's chemical structure. Both water-soluble and water-insoluble compounds can be quantified by this method. Although the throughput of this assay is lower than that of radiometric methods, the assay is easier to set up and cheaper, and avoids the problems related to radioactive waste disposal.

  13. Children's memory distortions following social contact with a co-witness: disentangling social and cognitive mechanisms.

    PubMed

    Bright-Paul, Alexandra; Jarrold, Christopher; Wright, Daniel B; Guillaume, Stephanie

    2012-01-01

    This study examined whether recalling an event with a co-witness influences children's recall. Individual 3-5-year-olds (n = 48) watched a film with a co-witness. Unbeknown to participants, the co-witness was watching an alternative version of the film. Afterwards both the co-witness and the participant answered questions about the film together (public recall), and the degree to which children conformed to the co-witness's alternative version of events was measured. Subsequently participants were questioned again individually (private recall). Children also completed false belief and inhibitory control tasks. By separating errors made in public and private, the results indicated that both social conformity (32% of errors) and memory distortion (68% of errors) played a role in co-witness influence. Inhibitory control predicted the likelihood of retracting errors in private, but only for children who failed (r = .66) rather than passed false belief tasks (r = -.10). The results suggest that children with a theory of mind conform in the company of the co-witness to avoid social embarrassment, while those a poor theory of mind conform on the basis of an inability to inhibit the co-witness's response. The findings contribute to our understanding of the motivations responsible for co-witness conformity across early childhood.

  14. Posttraumatic stress disorder in the nursing population: a concept analysis.

    PubMed

    Mealer, Meredith; Jones, Jacqueline

    2013-01-01

    This article is a report of an analysis of the concept of posttraumatic stress disorder (PTSD) and its application to the nursing population. Nurses are at an increased risk for work-related stress resulting in retention issues and impaired functioning in work and home environment. The nursing discipline has been inconsistent with the concepts used to describe the distress and resultant discussions related to the comprehensive nature of the distress experienced, heavily focusing on existing medical language that emphasizes disorders and psychopathology. Walker and Avant's strategy for concept analysis was used in this analysis. A literature review for 1994-2011 was conducted for the following keywords: secondary traumatic stress, compassion fatigue, vicarious traumatization, posttraumatic stress disorder, and nurse. The concept of posttraumatic stress disorder in the nursing population is best described within the context of the Nurse as Wounded Healer theory. Essential attributes include intrusions, avoidance, and hyperarousal. The consequences include worldview changes, retention issues, sleep disruption, and social network disturbances. This concept analysis viewed through The Nurse as Wounded Healer lens, offers clarity to the concept of PTSD within the nursing population and identifies limitations to prior conceptualizations. © 2013 Wiley Periodicals, Inc.

  15. Guidewire retention following central venous catheterisation: a human factors and safe design investigation.

    PubMed

    Horberry, Tim; Teng, Yi-Chun; Ward, James; Patil, Vishal; Clarkson, P John

    2014-01-01

    Central Venous Catheterisation (CVC) has occasionally been associated with cases of retained guidewires in patients after surgery. In theory, this is a completely avoidable complication; however, as with any human procedure, operator error leading to guidewires being occasionally retained cannot be fully eliminated. The work described here investigated the issue in an attempt to better understand it both from an operator and a systems perspective, and to ultimately recommend appropriate safe design solutions that reduce guidewire retention errors. Nine distinct methods were used: observations of the procedure, a literature review, interviewing CVC end-users, task analysis construction, CVC procedural audits, two human reliability assessments, usability heuristics and a comprehensive solution survey with CVC end-users. The three solutions that operators rated most highly, in terms of both practicality and effectiveness, were: making trainees better aware of the potential guidewire complications and strongly emphasising guidewire removal in CVC training, actively checking that the guidewire is present in the waste tray for disposal, and standardising purchase of central line sets so that differences that may affect chances of guidewire loss is minimised. Further work to eliminate/engineer out the possibility of guidewires being retained is proposed.

  16. Hierarchical columnar silicon anode structures for high energy density lithium sulfur batteries

    NASA Astrophysics Data System (ADS)

    Piwko, Markus; Kuntze, Thomas; Winkler, Sebastian; Straach, Steffen; Härtel, Paul; Althues, Holger; Kaskel, Stefan

    2017-05-01

    Silicon is a promising anode material for next generation lithium secondary batteries. To significantly increase the energy density of state of the art batteries with silicon, new concepts have to be developed and electrode structuring will become a key technology. Structuring is essential to reduce the macroscopic and microscopic electrode deformation, caused by the volume change during cycling. We report pulsed laser structuring for the generation of hierarchical columnar silicon films with outstanding high areal capacities up to 7.5 mAh cm-2 and good capacity retention. Unstructured columnar electrodes form a micron-sized block structure during the first cycle to compensate the volume expansion leading to macroscopic electrode deformation. At increased silicon loading, without additional structuring, pronounced distortion and the formation of cracks through the current collector causes cell failure. Pulsed laser ablation instead is demonstrated to avoid macroscopic electrode deformation by initial formation of the block structure. A full cell with lithiated silicon versus a carbon-sulfur cathode is assembled with only 15% overbalanced anode and low electrolyte amount (8 μl mgsulfur-1). While the capacity retention over 50 cycles is identical to a cell with high excess lithium anode, the volumetric energy density could be increased by 30%.

  17. Enhanced lithium ion battery cycling of silicon nanowire anodes by template growth to eliminate silicon underlayer islands.

    PubMed

    Cho, Jeong-Hyun; Picraux, S Tom

    2013-01-01

    It is well-known that one-dimensional nanostructures reduce pulverization of silicon (Si)-based anode materials during Li ion cycling because they allow lateral relaxation. However, even with improved designs, Si nanowire-based structures still exhibit limited cycling stability for extended numbers of cycles, with the specific capacity retention with cycling not showing significant improvements over commercial carbon-based anode materials. We have found that one important reason for the lack of long cycling stability can be the presence of milli- and microscale Si islands which typically form under nanowire arrays during their growth. Stress buildup in these Si island underlayers with cycling results in cracking, and the loss of specific capacity for Si nanowire anodes, due to progressive loss of contact with current collectors. We show that the formation of these parasitic Si islands for Si nanowires grown directly on metal current collectors can be avoided by growth through anodized aluminum oxide templates containing a high density of sub-100 nm nanopores. Using this template approach we demonstrate significantly enhanced cycling stability for Si nanowire-based lithium-ion battery anodes, with retentions of more than ~1000 mA·h/g discharge capacity over 1100 cycles.

  18. Something worth remembering: visual discrimination in sharks.

    PubMed

    Fuss, Theodora; Schluessel, Vera

    2015-03-01

    This study investigated memory retention capabilities of juvenile gray bamboo sharks (Chiloscyllium griseum) using two-alternative forced-choice experiments. The sharks had previously been trained in a range of visual discrimination tasks, such as distinguishing between squares, triangles and lines, and their corresponding optical illusions (i.e., the Kanizsa figures or Müller-Lyer illusions), and in the present study, we tested them for memory retention. Despite the absence of reinforcement, sharks remembered the learned information for a period of up to 50 weeks, after which testing was terminated. In fish, as in other vertebrates, memory windows vary in duration depending on species and task; while it may seem beneficial to retain some information for a long time or even indefinitely, other information may be forgotten more easily to retain flexibility and save energy. The results of this study indicate that sharks are capable of long-term memory within the framework of selected cognitive skills. These could aid sharks in activities such as food retrieval, predator avoidance, mate choice or habitat selection and therefore be worth being remembered for extended periods of time. As in other cognitive tasks, intraspecific differences reflected the behavioral breadth of the species.

  19. Spatial learning in rats: correlation with cortical choline acetyltransferase and improvement with NGF following NBM damage.

    PubMed

    Mandel, R J; Gage, F H; Thal, L J

    1989-06-01

    Rats display an acquisition deficit in a circular water maze following excitotoxic lesions of the nucleus basalis magnocellularis (NBM). Experiments were therefore performed to determine if acquisition behavior on this task could predict the degree of cortical cholinergic deafferentation and if the acquisition deficit could be pharmacologically reversed. Performance on acquisition was highly correlated with the lesion-induced reduction in cortical choline acetyltransferase (ChAT) activity. Accuracy of spatial behavior was highly correlated to percentage ChAT depletion (r = 0.75). Neither lesioned rats nor controls displayed a retention deficit after a 9-day interval, nor did either group display a passive-avoidance retention deficit. To test the causal relationship between cholinergic dysfunction and spatial behavior, the central nervous system cholinergic enhancer nerve growth factor (NGF) was intraventricularly infused for 4 weeks. NGF infusion resulted in improved acquisition of the water maze task compared to NBM-lesioned rats receiving vehicle infusion and untreated rats with NBM lesions. These studies indicate that the decrease in cortical ChAT activity is likely to be responsible for the observed acquisition deficit and that pharmacological manipulations can be successfully used to improve behavior following NBM lesions.

  20. Edgar Dale's Pyramid of Learning in medical education: a literature review.

    PubMed

    Masters, Ken

    2013-11-01

    Edgar Dale's Pyramid of Learning and percentages of retained learning are cited in educational literature in a range of disciplines. The sources of the Pyramid, however, are misleading. To examine the evidence supporting the Pyramid and the extent to which it is cited in medical education literature. A review of literature (1946-2012) based on a search utilising Academic Search Complete, CINAHL, Medline and Google Scholar conducted from September to November 2012. A total of 43 peer-reviewed medical education journal articles and conference papers were found. While some researchers had been misled by their sources, other authors' interpretations of the citations did not align with the content of those citations, had no such citations, had circular references, or consulted questionable sources. There was no agreement on the percentages of learning retention, in spite of many researchers' citing primary texts. The inappropriate citing of the Pyramid and its associated percentages in medical education literature is widespread and continuous. This citing undermines much of the published work, and impacts on research-based medical education literature. While the area of learning/teaching strategies and amount of retention from each is an area for future research, any reference to the Pyramid should be avoided.

  1. Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology.

    PubMed

    Bisogni, Valeria; Rossi, Gian Paolo; Calò, Lorenzo A

    2014-06-01

    The glicyrrhizic acid, contained in licorice, has a mineralcorticoid-like effect. Chronic excess intake of licorice induces the rare syndrome of "apparent mineralcorticoid excess", due to the inhibitory effect of glicyrrhizic acid on 11 β-hydroxysteroid dehydrogenase type 2 determining clinical/biochemical manifestations as resistant hypertension, metabolic alkalosis and severe hypokalemia. We report a typical clinical case of licorice abuse to emphasize the importance of a detailed anamnesis, which is essential for the diagnosis, avoid unnecessary and expensive investigations, and reduce the duration of hospitalization. We also provide an appraisal of the pathophysiology of "apparent mineralcorticoid excess" syndrome, still an often forgotten or unrecognized cause of hypokalemia and hypertension.

  2. Home fire safety education for parents of newborns.

    PubMed

    Lehna, Carlee; Fahey, Erin; Janes, Erika G; Rengers, Sharon; Williams, Joseph; Scrivener, Drane; Myers, John

    2015-09-01

    In children under 1 year of age, the proportion of unintentional burns increases with infant age and mobility. Infants are not able to avoid burns and are dependent on parental or adult help. Treatment of burns in young children is expensive in terms of the life-long costs. The purpose of this study was to examine changes in home fire safety (HFS) knowledge and practices over time for parents of newborn children and expecting parents. HFS knowledge of 103 parents was assessed at baseline, immediately after watching a DVD on HFS (recall), and at 2-week follow-up (retention). In addition, the United States Fire Administration (USFA)/Federal Emergency Management Agency (FEMA) Home Safety Checklist which examines HFS practices in the homes was administered. Seventy percent of the participants were Caucasian, 65% were married, and 81% were first-time parents. HFS knowledge increased significantly from baseline to recall (45±12% vs. 87±17% correct responses, p<0.0001), but declined to 75±18% correct at retention. That is, an individual's baseline scores nearly doubled at recall (42±11% change in baseline score), but only increased by 67% at retention (30±15% change in baseline score). For a subsample of parents who completed the USFA Checklist (n=22), the mean percentage of advocated practices followed was 71±11% (range: 40-89%). Using DVDs was an effective educational modality for increasing HFS knowledge. This addressed an important problem of decreasing burns in infants through increasing parent knowledge and HFS practices using a short, inexpensive DVD. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  3. Analysis of mechanisms for memory enhancement using novel and potent 5-HT1A receptor ligands.

    PubMed

    Pittalà, Valeria; Siracusa, Maria A; Salerno, Loredana; Romeo, Giuseppe; Modica, Maria N; Madjid, Nather; Ogren, Sven Ove

    2015-08-01

    In light of the involvement of serotonergic 5-HT1A receptors in the mediation of the memory of aversive events, the potent and selective 5-HT1A receptor antagonists, MC18 fumarate and VP08/34 fumarate, were tested in the passive avoidance task (PA), a rodent model of instrumental conditioning. Either alone or in combination with the prototypical agonist 8-OH-DPAT, MC18 fumarate at doses (0.1, 0.3 and 1mg/kg given 15min prior to training) exerted a dose-dependent facilitation of PA memory retention. When administered 15min prior to 8-OH-DPAT (0.3 and 1mg/kg), MC18 fumarate at a dose of 0.3mg/kg, enhanced significantly the impairment of PA retention caused by 8-OH-DPAT (1mg/kg). However, VP08/34 fumarate given at the same doses exerted no statistically effect on PA retention memory. Furthermore, VP08/34 fumarate given 15min prior to 8-OH-DPAT (0.3 and 1mg/kg) only slightly enhanced the PA impairment induced by 8-OH-DPAT. In conclusion, the profile of MC18 fumarate is intriguing since it behaves in a manner which differs from both full receptor antagonists such as NAD-299 or partial receptor agonists. The results also illustrate the importance of subtle receptor interaction and probably ligand efficacy in determining the actions of two almost identical 5-HT1A receptor ligands in cognitive function such as instrumental learning. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  4. Adaptive Virtual Reality Training to Optimize Military Medical Skills Acquisition and Retention.

    PubMed

    Siu, Ka-Chun; Best, Bradley J; Kim, Jong Wook; Oleynikov, Dmitry; Ritter, Frank E

    2016-05-01

    The Department of Defense has pursued the integration of virtual reality simulation into medical training and applications to fulfill the need to train 100,000 military health care personnel annually. Medical personnel transitions, both when entering an operational area and returning to the civilian theater, are characterized by the need to rapidly reacquire skills that are essential but have decayed through disuse or infrequent use. Improved efficiency in reacquiring such skills is critical to avoid the likelihood of mistakes that may result in mortality and morbidity. We focus here on a study testing a theory of how the skills required for minimally invasive surgery for military surgeons are learned and retained. Our adaptive virtual reality surgical training system will incorporate an intelligent mechanism for tracking performance that will recognize skill deficiencies and generate an optimal adaptive training schedule. Our design is modeling skill acquisition based on a skill retention theory. The complexity of appropriate training tasks is adjusted according to the level of retention and/or surgical experience. Based on preliminary work, our system will improve the capability to interactively assess the level of skills learning and decay, optimizes skill relearning across levels of surgical experience, and positively impact skill maintenance. Our system could eventually reduce mortality and morbidity by providing trainees with the reexperience they need to help make a transition between operating theaters. This article reports some data that will support adaptive tutoring of minimally invasive surgery and similar surgical skills. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  5. How Do Allied Health Professionals Construe the Role of the Remote Workforce? New Insight into Their Recruitment and Retention.

    PubMed

    Campbell, Narelle; Eley, Diann S; McAllister, Lindy

    2016-01-01

    Allied health workforce recruitment and retention in remote areas is a global problem. Using case studies from the Australian allied health workforce, this paper adds new information by combining personality trait information with a detailed understanding of how the cases construe the demands of remote work, which may be useful in addressing this problem. Four cases (two urban, two remote) are presented from a mixed methods study (n = 562), which used (1) the Temperament and Character Inventory to investigate personality traits of allied health professionals; and (2) repertory grid interviews to reveal quantitatively and qualitatively how the cases construed their Ideal work role compared with their Current and a Remote role. Cases also self-assessed their fit ('suited' or 'not suited') with remote. Differences in the way cases construed their fit with remote work was related to prior experience. However all were satisfied with their work, perceiving their Current role as similar to their Ideal. All saw remote work as requiring generalist expertise and a reliance on relationships. Personality traits, especially Novelty Seeking and Harm Avoidance, fit with how allied health professionals perceived their role. The combination of two distinct lines of investigation, illustrates what more can be revealed about allied health professional's career choices by taking into account the fit or lack of fit between their personality tendencies, their construing of remote work and their life circumstances. Understanding the combined influence of perceptions and traits on an individual toward or away from remote work may enhance recruitment and retention internationally.

  6. How Do Allied Health Professionals Construe the Role of the Remote Workforce? New Insight into Their Recruitment and Retention

    PubMed Central

    Campbell, Narelle; Eley, Diann S.; McAllister, Lindy

    2016-01-01

    Purpose Allied health workforce recruitment and retention in remote areas is a global problem. Using case studies from the Australian allied health workforce, this paper adds new information by combining personality trait information with a detailed understanding of how the cases construe the demands of remote work, which may be useful in addressing this problem. Methods Four cases (two urban, two remote) are presented from a mixed methods study (n = 562), which used (1) the Temperament and Character Inventory to investigate personality traits of allied health professionals; and (2) repertory grid interviews to reveal quantitatively and qualitatively how the cases construed their Ideal work role compared with their Current and a Remote role. Cases also self-assessed their fit (‘suited’ or ‘not suited’) with remote. Findings Differences in the way cases construed their fit with remote work was related to prior experience. However all were satisfied with their work, perceiving their Current role as similar to their Ideal. All saw remote work as requiring generalist expertise and a reliance on relationships. Personality traits, especially Novelty Seeking and Harm Avoidance, fit with how allied health professionals perceived their role. Conclusions The combination of two distinct lines of investigation, illustrates what more can be revealed about allied health professional’s career choices by taking into account the fit or lack of fit between their personality tendencies, their construing of remote work and their life circumstances. Understanding the combined influence of perceptions and traits on an individual toward or away from remote work may enhance recruitment and retention internationally. PMID:27907073

  7. Clinical usefulness of novel tag-less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis.

    PubMed

    Nakamura, Masanao; Hirooka, Yoshiki; Yamamura, Takeshi; Miyahara, Ryoji; Watanabe, Osamu; Ando, Takafumi; Ohmiya, Naoki; Goto, Hidemi

    2015-01-01

    The Agile patency capsule (PC; Given Imaging Ltd, Yoqneam, Israel) is used as a dummy prior to capsule endoscopy (CE) to avoid retention of the CE capsule. However, impaction of the PC's inner radio frequency identification (RFID) tag in a stricture could cause small-bowel ileus. Recently, the RFID tag-less PC was introduced into clinical practice. Herein, we aimed to retrospectively evaluate the usefulness of the tag-less PC. Of 154 patients who were scheduled to undergo CE, 100 consecutive patients (65%) who underwent PC evaluation were enrolled in the present study. Primary study end point was the retention rate of the CE capsule after successful passage of the PC. Secondary end point was analysis of the significant factors affecting the passage of the PC. In total, 87 patients (87%) had bowel patency confirmed by PC evaluation. There was no capsule retention in any of these 87 patients during CE. Abnormal findings were obtained from 60 CE, and 41 patients received new or modified treatment. Multivariate analysis of factors related to the confirmation of patency demonstrated that stenosis on imaging was the most influential factor (P = 0.002, odds ratio 16.387). The results confirmed that passage of the PC depends on stenosis on imaging. Use of the tag-less PC confirmed gastrointestinal tract patency for most of the patients who did not have stenosis on imaging and allowed estimation of the patency for patients who did have stenosis on imaging. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

  8. Inactivation of Microorganisms

    NASA Astrophysics Data System (ADS)

    Alzamora, Stella Maris; Guerrero, Sandra N.; Schenk, Marcela; Raffellini, Silvia; López-Malo, Aurelio

    Minimal processing techniques for food preservation allow better retention of product flavor, texture, color, and nutrient content than comparable conventional treatments. A wide range of novel alternative physical factors have been intensely investigated in the last two decades. These physical factors can cause inactivation of microorganisms at ambient or sublethal temperatures (e.g., high hydrostatic pressure, pulsed electric fields, ultrasound, pulsed light, and ultraviolet light). These technologies have been reported to reduce microorganism population in foods while avoiding the deleterious effects of severe heating on quality. Among technologies, high-energy ultrasound (i.e., intensities higher than 1 W/cm2, frequencies between 18 and 100 kHz) has attracted considerable interest for food preservation applications (Mason et al., 1996; Povey and Mason, 1998).

  9. Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile.

    PubMed

    Phillips, Andrew N; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Apollo, Tsitsi; Murungu, Joseph; Rousseau, Christine; Garnett, Geoff; Ehrenkranz, Peter; Bansi-Matharu, Loveleen; Vojnov, Lara; Katz, Zachary; Peeling, Rosanna; Revill, Paul

    2016-09-01

    Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results not received, use of an approach that best facilitates retention on ART, and the ability to facilitate greater use of differentiated care, including through expanding coverage of testing availability.

  10. Pseudo-hemothorax at computed tomography due to residual contrast media.

    PubMed

    Romero, Matías; Bächler, Pablo

    2014-01-01

    Pleural effusion is a clinical problem that has many causes, with hemothorax being one of them. Computed tomography readily characterizes pleural fluid with determination of the attenuation value, helping to distinguish hemothorax from other types of effusion. Herein, we report the case of a 67-year-old man with end-stage renal disease in which a high-density pleural effusion due to residual contrast media was misinterpreted as hemothorax. Radiologists should consider the possibility of contrast media retention when interpreting a high-density pleural effusion in patients with end-stage renal disease. Recognition of this entity is crucial to avoid misdiagnosis, which might lead to unnecessary testing or procedures. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Transrectal ultrasound-guided extraction of impacted prostatic urethral calculi: a simple alternative to endoscopy

    PubMed Central

    Amend, Gregory; Gandhi, Jason; Smith, Noel L.; Weissbart, Steven J.; Schulsinger, David A.; Joshi, Gargi

    2017-01-01

    Urethral stones can become impacted in the posterior urethra, typically presenting with varying degrees of acute urinary retention and lower urinary tract symptoms. These are traditionally treated in the inpatient setting, with external urethrotomy or endoscopic push-back of the calculus into the urinary bladder followed by cystolitholapaxy or cystolithotripsy. However, these methods are invasive, involve general anesthesia, and require radiation. In this report, we describe a simple, minimally invasive, and safe alternative technique to visualize and remove impacted prostatic urethral stones under the real-time guidance of transrectal ultrasonography (TRUS). The urologist can accomplish this procedure in the office, avoiding radiation exposure to the patient and hospital admission. PMID:28725602

  12. RETORT ASSEMBLY

    DOEpatents

    Loomis, C.C.; Ash, W.J.

    1957-11-26

    An improved retort assembly useful in the thermal reduction of volatilizable metals such as magnesium and calcium is described. In this process a high vacuum is maintained in the retort, however the retort must be heated to very high temperatures while at the same time the unloading end must bo cooled to condense the metal vapors, therefore the retention of the vacuum is frequently difficult due to the thermal stresses involved. This apparatus provides an extended condenser sleeve enclosed by the retort cover which forms the vacuum seal. Therefore, the seal is cooled by the fluid in the condenser sleeve and the extreme thermal stresses found in previous designs together with the deterioration of the sealing gasket caused by the high temperatures are avoided.

  13. Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile

    PubMed Central

    Phillips, Andrew N.; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Apollo, Tsitsi; Murungu, Joseph; Rousseau, Christine; Garnett, Geoff; Ehrenkranz, Peter; Bansi-Matharu, Loveleen; Vojnov, Lara; Katz, Zachary; Peeling, Rosanna; Revill, Paul

    2016-01-01

    Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results not received, use of an approach that best facilitates retention on ART, and the ability to facilitate greater use of differentiated care, including through expanding coverage of testing availability. PMID:27704016

  14. In vitro interactions between amphotericin B and hydrocortisone: potential implications for intrathecal therapy.

    PubMed

    Hodge, Greg; Cohen, Stuart H; Thompson, George R

    2015-09-01

    Fungal meningitis remains a severe and often lethal infection requiring aggressive antifungal therapy and in refractory cases the use of intrathecal amphotericin B (AmB). Administration of amphotericin B by this method may result in clinically apparent adverse reactions such as paresthesias, radiculitis, or myelopathy. Coadministration of hydrocortisone is therefore often given in an attempt to avoid these effects; however, the potential consequences of this approach on fungal growth or on drug synergy/antagonism had not previously been assessed. We used the checkerboard titration broth microdilution method to analyze interactions by fractional inhibitory concentration indices (FICIs). The combination of amphotericin B and hydrocortisone resulted in synergy or indifference against all isolates (Candida, Cryptococcus, and Coccidioides) during in vitro testing at low concentrations. Antagonism was observed using higher hydrocortisone concentrations (those not observed in vivo) suggesting possible steric hindrance or binding to AmB may occur at doses unlikely to be present during clinical care. Concurrent hydrocortisone and AmB administration should not be avoided due to in vitro antagonism concerns. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Opposite roles for neuropeptide S in the nucleus accumbens and bed nucleus of the stria terminalis in learned helplessness rats.

    PubMed

    Shirayama, Yukihiko; Ishima, Tamaki; Oda, Yasunori; Okamura, Naoe; Iyo, Masaomi; Hashimoto, Kenji

    2015-09-15

    The role of neuropeptide S (NPS) in depression remains unclear. We examined the antidepressant-like effects of NPS infusions into the shell or core regions of the nucleus accumbens (NAc) and into the bed nucleus of the stria terminalis (BNST) of learned helplessness (LH) rats (an animal model of depression). Infusions of NPS (10 pmol/side) into the NAc shell, but not the NAc core and BNST, exerted antidepressant-like effects in the LH paradigm. Implying that behavioral deficits could be improved in the conditioned avoidance test. Coinfusion of SHA68 (an NPS receptor antagonist, 100 pmol/side) with NPS into the NAc shell blocked these effects. In contrast, NPS receptor antagonism by SHA68 in the BNST induced antidepressant-like effects. Infusions of NPS into the NAc shell or SHA68 into the BNST did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. These results suggest that excitatory and inhibitory actions by the NPS system are integral to the depression in LH animals. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.

    PubMed

    Zikopoulos, Basilis; Höistad, Malin; John, Yohan; Barbas, Helen

    2017-05-17

    The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders. SIGNIFICANCE STATEMENT The dialogue between prefrontal cortex and amygdala allows thoughts and emotions to influence actions. The posterior orbitofrontal cortex sends a powerful pathway that targets a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose wiring may help modulate autonomic function. By contrast, the anterior cingulate cortex innervates other amygdalar parts, activating circuits to help avoid danger. Most IM neurons in primates label for the protein DARPP-32, known to be activated or inhibited based on the level of dopamine. Stress markedly increases dopamine release and inhibits IM neurons, compromises prefrontal control of the amygdala, and sets off a general alarm system as seen in affective disorders, such as chronic anxiety and post-traumatic stress disorder. Copyright © 2017 the authors 0270-6474/17/375051-14$15.00/0.

  17. Effect of pregabalin on fear-based conditioned avoidance learning and spatial learning in a mouse model of scopolamine-induced amnesia.

    PubMed

    Sałat, Kinga; Podkowa, Adrian; Malikowska, Natalia; Trajer, Jędrzej

    2017-03-01

    Cognitive deficits are one of the frequent symptoms accompanying epilepsy or its treatment. In this study, the effect on cognition of intraperitoneally administered antiepileptic drug, pregabalin (10 mg/kg), was investigated in scopolamine-induced memory-impaired mice in the passive avoidance task and Morris water maze task. The effect of scopolamine and pregabalin on animals' locomotor activity was also studied. In the retention phase of the passive avoidance task, pregabalin reversed memory deficits induced by scopolamine (p < 0.05). During the acquisition phase of the Morris water maze pregabalin-treated memory-impaired mice performed the test with longer escape latencies than the vehicle-treated mice (significant at p < 0.05 on Day 5, and at p < 0.001 on Day 6). There were no differences in this parameter between the scopolamine-treated control group and pregabalin-treated memory-impaired mice, which indicated that pregabalin had no influence on spatial learning in this task. During the probe trial a significant difference (p < 0.05) was observed in terms of the mean number of target crossings between vehicle-treated mice and pregabalin-treated memory-impaired mice but there was no difference between the scopolamine-treated control group and mice treated with pregabalin + scopolamine. Pregabalin did not influence locomotor activity increased by scopolamine. In passive avoidance task, pregabalin reversed learning deficits induced by scopolamine. In the Morris water maze, pregabalin did not influence spatial learning deficits induced by scopolamine. These results are relevant for epileptic patients treated with pregabalin and those who use it for other therapeutic indications (anxiety, pain).

  18. A rapid throughput approach identifies cognitive deficits in adult zebrafish from developmental exposure to polybrominated flame retardants.

    PubMed

    Truong, Lisa; Mandrell, David; Mandrell, Rick; Simonich, Michael; Tanguay, Robert L

    2014-07-01

    A substantial body of evidence has correlated the human body burdens of some polybrominated diphenyl ether (PBDE) flame retardants with cognitive and other behavioral deficits. Adult zebrafish exhibit testable learning and memory, making them an increasingly attractive model for neurotoxicology. Our goal was to develop a rapid throughput means of identifying the cognitive impact of developmental exposure to flame retardants in the zebrafish model. We exposed embryos from 6h post fertilization to 5 days post fertilization to either PBDE 47 (0.1μM), PBDE 99 (0.1μM) or PBDE 153 (0.1μM), vehicle (0.1% DMSO), or embryo medium (EM). The larvae were grown to adulthood and evaluated for the rate at which they learned an active-avoidance response in an automated shuttle box array. Zebrafish developmentally exposed to PBDE 47 learned the active avoidance paradigm significantly faster than the 0.1% DMSO control fish (P<0.0001), but exhibited significantly poorer performance when retested suggestive of impaired memory retention or altered neuromotor activity. Learning in the PBDE 153 group was not significantly different from the DMSO group. Developmental exposure to 0.1% DMSO impaired adult active avoidance learning relative to the sham group (n=39; P<0.0001). PBDE 99 prevented the DMSO effect, yielding a learning rate not significantly different from the sham group (n=36; P>0.9). Our results underscore the importance of vehicle choice in accurately assessing chemical effects on behavior. Active avoidance response in zebrafish is an effective model of learning that, combined with automated shuttle box testing, will provide a highly efficient platform for evaluating persistent neurotoxic hazard from many chemicals. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2, MMP-9, and MAPKs in Adult Mice.

    PubMed

    SoukhakLari, Roksana; Moezi, Leila; Pirsalami, Fatema; Moosavi, Maryam

    2018-06-24

    Although high rate of curcumin consumption has been suggested to decrease the prevalence of Alzheimer's disease (AD), its administration has no effect on the progression of AD in humans and this has been attributed to its poor bioavailability. Using nanotechnology to break down curcumin increases its bioavailability and improves its effect on the brain. BSA, as a non-toxic protein with high binding capacity, was used to break curcumin to nanosize and to explore the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and -9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were administered to male NMRI mice weighing 20-25 g for 10 days. Passive avoidance training was performed on day 10 and 24 h after, a retention trial was done. Upon completion of behavioral studies, the hippocampi were isolated and western blot analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses resulted in a significantly improved performance in passive avoidance memory test while its equivalent doses of natural curcumin did not produce a similar effect. In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p-ERK and a decrease in p-JNK. This study indicates that breaking curcumin to nanosize produces improved effects on passive avoidance memory in adult mice accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus.

  20. Proline-rich proteins moderate the inhibitory effect of tea on iron absorption in rats.

    PubMed

    Kim, Hee-Seon; Miller, Dennis D

    2005-03-01

    Tea inhibits iron absorption in studies in which tea is given with radiolabeled iron to humans as a single dose. Our objective was to test the hypothesis that proline-rich proteins (PRPs) may act as a defense against this effect by forming complexes with tannins, thereby preventing them from inhibiting iron absorption. Two studies were conducted. In study 1, rats were given test solutions containing (59)FeCl(3) in water, tea, or tea + gelatin (T/G). In study 2, the rats were divided into 3 groups and assigned to one of 3 nutritionally complete diets: control, tea (5 g tea tannin/kg diet), or T/G (5 g tea tannin + 60 g gelatin/kg diet). Rats were fed the respective diets for 5 d and then given a single (59)Fe-labeled meal of the diet. Iron absorption was measured by whole-body retention of the (59)Fe over a 2-wk period. Iron absorption in study 1 was lower in the tea group (24 +/- 9.6%, P < 0.05) than in the T/G (42 +/- 19.4%) or water groups (50 +/- 7.5%). In study 2, iron absorption did not differ among the groups. Rats fed the tea diet had dramatic hypertrophy of the parotid salivary glands. Adding gelatin as a proxy for salivary PRPs to the tea eliminated the inhibitory effect of tea on iron absorption. The results suggest that PRPs, whether from salivary glands or diet, can protect against the inhibition of iron absorption by tea.

  1. Optimisation of sewage sludge anaerobic digestion through co-digestion with OFMSW: Effect of collection system and particle size.

    PubMed

    Silvestre, Gracia; Bonmatí, August; Fernández, Belén

    2015-09-01

    The effect of organic fraction of municipal solid waste (OFMSW) loading rate and particulate size on the sewage sludge (SS) mesophilic anaerobic co-digestion was assessed in continuous stirred tank reactor at hydraulic retention time of 20days. The SS-OFMSW mixture composed by 54% of the volatile solids fed (inlet-VS), at OLR of 3.1kgCODm(-3)d(-1) (1.9kgVSm(-3)d(-1)), showed the highest increment on the volumetric methane production and yield of +200% and +59% respectively, under stable conditions. The effect of particulate size was assessed with the same mixture and same operational conditions but reducing the OFMSW particulate size from 20mm to 8mm with the aim to improve the hydrolysis step, but the results showed any influence in the OFMSW particulate size range analysed. In addition, specific biomass activity was assessed at the end of each co-digestion period. Results showed that OFMSW promoted β-oxidation syntrophic acetogens and the acetoclastic methanogens activity; although the last increase of the OFMSW percentage (from 47% to 54% inlet-VS) affected negatively the specific substrate activity, but not inhibitory effect was observed. Therefore, the results obtained in the continuous experiment could be related with some inhibitory or toxic effect and not due to hydrolysis limitation. The specific biomass activity test was demonstrated to be an interesting tool to evaluate and control the co-digestion process, especially when conventional parameters did not explain the behaviour of the biological system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Administration of nicotinic receptor antagonists during the period of memory consolidation affects passive avoidance learning and modulates synaptic efficiency in the CA1 region in vivo.

    PubMed

    Dobryakova, Y V; Gurskaya, O Ya; Markevich, V A

    2015-01-22

    We examined whether a non-selective antagonist of nAChRs mecamylamine and selective antagonists of α4β2-containing nAChRs dihydro-β-erythroidine (DHβE) and α7-containing nAChRs methyllycaconitine (MLA) affect learning performance and synaptic efficiency in the CA1 area of the hippocampus of freely moving rats during the memory consolidation period. Adult male Wistar rats received mecamylamine (0.5 mg/kg), DHβE (1 mg/kg), MLA (2 mg/kg) or saline immediately after training in a passive avoidance task. Memory retention was examined 24 h after the training. The changes in the latency of the first entry into a dark compartment of a test chamber were chosen as a criterion of learning. The ability of nAChRs antagonists to induce changes in the basal level of focal potentials (fEPSP, field excitatory postsynaptic potential) was estimated before training (baseline), 90 min after the training (consolidation period) and 24 h after the training (retention period). We found that in untrained rats mecamylamine, DHβE and MLA diminished the amplitude of fEPSP within the first 90 min after the injection; similar effect was observed in DHβE- and MLA-treated trained animals. These suppressive effects of DHβE and MLA were associated with memory loss. In contrast, mecamylamine, when applied to trained animals, tended to increase latency to enter the dark chamber and did not influence fEPSP during first 90 min after injection. Thus, the nAChRs antagonists with different selectivity induced different changes in fEPSP and behavior which suggests that nAChRs with different subunit composition are diversely involved in memory consolidation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Effect of a gelatin-based edible coating containing cellulose nanocrystals (CNC) on the quality and nutrient retention of fresh strawberries during storage

    NASA Astrophysics Data System (ADS)

    Fakhouri, F. M.; Casari, A. C. A.; Mariano, M.; Yamashita, F.; Innocnentini Mei, L. H.; Soldi, V.; Martelli, S. M.

    2014-08-01

    Strawberry is a non-climacteric fruit with a very short postharvest shelf-life. Loss of quality in this fruit is mostly due to its relatively high metabolic activity and sensitivity to fungal decay, meanly grey mold (Botrytis cinerea). In this study, the ability of gelatin coatings containing cellulose nanocrystals (CNC) to extend the shelf-life of strawberry fruit (Fragaria ananassa) over 8 days were studied. The filmogenic solution was obtained by the hydration of 5 g of gelatin (GEL) in 100 mL of distillated water containing different amounts of CNC dispersion (10 mg CNC/g of GEL or 50 mg of CNC/g of GEL) for 1 hour at room temperature. After this period, the solution was heated to 70 °C and maintained at this temperature for 10 minutes. The plasticizer (glycerol) (10g/100g of the GEL) was then added with constant, gentle stirring in order to avoid forming air bubbles and also to avoid gelatin denaturation until complete homogenization. Strawberries (purchased at the local market) were immersed in the filmogenic solution for 1 minute and after coated were dried at 15 °C by 24 hours. The strawberries were then kept under refrigeration and characterized in terms of their properties (weight loss, ascorbic acid content, titratable acidity, water content). The results have shown that samples covered with GEL/CNC had a significant improvement in its shelf- life. For instance, for the control sample (without coating) the weight loss after 8 days of storage was around 65%, while covered samples loss in the range of 31-36%. Edible coating was also effective in the retention of ascorbic acid (AA) in the strawberries, while control sample presented a fast decay in the AA content, covered samples showed a slow decay in the AA concentration. Moreover, the use of GEL/CNC edible coating had an antimicrobial effect in the fruits.

  4. 5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

    PubMed

    Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

    2012-11-01

    This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Inhibitory effect of cyanide on wastewater nitrification determined using SOUR and RNA-based gene-specific assays.

    PubMed

    Kapoor, V; Elk, M; Li, X; Santo Domingo, J W

    2016-08-01

    The effect of cyanide (CN(-) ) on nitrification was examined with samples from nitrifying bacterial enrichments using two different approaches: by measuring substrate (ammonia) specific oxygen uptake rates (SOUR), and by using RT-qPCR to quantify the transcripts of functional genes involved in nitrification. The nitrifying bioreactor was operated as a continuous reactor with a 24 h hydraulic retention time. The samples were exposed in batch vessels to cyanide for a period of 12 h. The concentrations of CN(-) used in the batch assays were 0·03, 0·06, 0·1 and 1·0 mg l(-1) . There was considerable decrease in SOUR with increasing dosages of CN(-) . A decrease of more than 50% in nitrification activity was observed at 0·1 mg l(-1) CN(-) . Based on the RT-qPCR data, there was notable reduction in the transcript levels of amoA and hao for increasing CN(-) dosage, which corresponded well with the ammonia oxidation activity measured via SOUR. The inhibitory effect of cyanide may be attributed to the affinity of cyanide to bind ferric haeme proteins, which disrupt protein structure and function. The correspondence between the relative expression of functional genes and SOUR shown in this study demonstrates the efficacy of RNA-based function-specific assays for better understanding of the effect of toxic compounds on nitrification activity in wastewater. The effect of cyanide on nitrifying bacteria was characterized by measuring physiological and transcriptional response. Cyanide was inhibitory to nitrification at concentrations that may be found in industrial waste. The RNA-based function-specific assays represent a mechanistic approach for better understanding the effect of toxic compounds on nitrification activity in wastewater. Moreover, the relative abundance of RNA transcripts can be used to closely track in situ nitrifying bacterial activity which can be used to predict inhibition events, thereby providing a metric to potentially improve performance of wastewater nitrifying systems. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  6. Residual effect of storage in an elevated carbon dioxide atmosphere on the microbial flora of rock cod (Sebastes spp. )

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, M.Y.; Ogrydziak, D.M.

    1986-10-01

    A residual inhibitory effect on microbial growth due to modified-atmosphere (MA) storage (MA, 80% CO/sub 2/-20% air) was demonstrated for rock cod fillets stored in MA and transferred to air at 4/sup 0/C. Results of measurements of CO/sub 2/ concentrations of the fillets suggested that the residual effect after transfer from MA to air was not due to retention of CO/sup 2/ at the surface of the fillets but was probably due to the microbial ecology of the system. Lactobacillus spp. and tan Alteromonas spp. (TAN) predominated after 7 and 14 days of storage in MA. During storage in MA,more » Pseudomonas spp. were inhibited or killed. Following transfer from MA to air, the percentage of the total flora represented by Lactobacillus spp. and TAN bacteria decreased, and 6 days after transfer Pseudomonas spp. were again dominant.« less

  7. The role of NPY in learning and memory.

    PubMed

    Gøtzsche, C R; Woldbye, D P D

    2016-02-01

    High levels of NPY expression in brain regions important for learning and memory together with its neuromodulatory and neurotrophic effects suggest a regulatory role for NPY in memory processes. Therefore it is not surprising that an increasing number of studies have provided evidence for NPY acting as a modulator of neuroplasticity, neurotransmission, and memory. Here these results are presented in relation to the types of memory affected by NPY and its receptors. NPY can exert both inhibitory and stimulatory effects on memory, depending on memory type and phase, dose applied, brain region, and NPY receptor subtypes. Thus NPY act as a resilience factor by impairing associative implicit memory after stressful and aversive events, as evident in models of fear conditioning, presumably via Y1 receptors in the amygdala and prefrontal cortex. In addition, NPY impairs acquisition but enhances consolidation and retention in models depending on spatial and discriminative types of associative explicit memory, presumably involving Y2 receptor-mediated regulations of hippocampal excitatory transmission. Moreover, spatial memory training leads to increased hippocampal NPY gene expression that together with Y1 receptor-mediated neurogenesis could constitute necessary steps in consolidation and long-term retention of spatial memory. Altogether, NPY-induced effects on learning and memory seem to be biphasic, anatomically and temporally differential, and in support of a modulatory role of NPY at keeping the system in balance. Obtaining further insight into memory-related effects of NPY could inspire the engineering of new therapeutics targeting diseases where impaired learning and memory are central elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    PubMed Central

    Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

    2014-01-01

    Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

  9. Use of a pooled clone method to isolate a novel Bacillus thuringiensis Cry2A toxin with activity against Ostrinia furnacalis.

    PubMed

    Shu, Changlong; Zhang, Jingtao; Chen, Guihua; Liang, Gemei; He, Kanglai; Crickmore, Neil; Huang, Dafang; Zhang, Jie; Song, Fuping

    2013-09-01

    A pooled clone method was developed to screen for cry2A genes. This metagenomic method avoids the need to analyse isolated Bacillus thuringiensis strains by performing gene specific PCR on plasmid-enriched DNA prepared from a pooled soil sample. Using this approach the novel holotype gene cry2Ah1 was cloned and characterized. The toxin gene was over-expressed in Escherichia coli Rosetta (DE3) and the expressed toxin accumulated in both the soluble and insoluble fractions. The soluble Cry2Ah1 was found to have a weight loss activity against Ostrinia furnacalis, and a growth inhibitory activity to both Cry1Ac-susceptible and resistant Helicoverpa armigera populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Homicide during postictal psychosis.

    PubMed

    Eisenschenk, Stephan; Krop, Harry; Devinsky, Orrin

    2014-01-01

    Postictal psychosis is characterized by a fluctuating combination of thought disorder, auditory and visual hallucinations, delusions, paranoia, affective change, and aggression including violent behavior. We present a case of homicide following a cluster of seizures. The patient's history and postictal behavior were his consistent with postictal psychosis. Contributing factors resulting in homicide may have included increased seizure frequency associated with a change in his AED regimen seizure frequency. The AED change to levetiracetam may also have increased impulsiveness with diminished mood regulation following discontinuation of carbamazepine. There is evidence that he had a cluster of seizures immediately prior to the murder which may have resulted in the postictal disinhibition of frontal lobe inhibitory systems. This homicide and other violent behaviors associated with postictal psychosis may be avoided with earlier recognition and treatment.

  11. A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory.

    PubMed

    Luft, Tatiana; Flores, Debora G; Vianna, Monica R M; Schwartsmann, Gilberto; Roesler, Rafael; Izquierdo, Ivan

    2006-06-26

    Although the gastrin-releasing peptide receptor has been implicated in memory consolidation, previous studies have not examined whether it is involved in extinction. Here we show that gastrin-releasing peptide receptor blockade in the hippocampus disrupts extinction of aversive memory. Male rats were trained in inhibitory avoidance conditioning and then returned repeatedly to the training context without shock on a daily basis for 3 days. Infusion of a gastrin-releasing peptide receptor antagonist or the protein synthesis inhibitor anisomycin into the dorsal hippocampus immediately after the first extinction session blocked extinction. These drugs did not affect performance in subsequent sessions when the first extinction session (1 day after training) was omitted. The results indicate that hippocampal gastrin-releasing peptide receptors are involved in memory extinction.

  12. Amelioration of scopolamine-induced amnesia by phosphatidylserine and curcumin in the day-old chick.

    PubMed

    Barber, Teresa A; Edris, Edward M; Levinsky, Paul J; Williams, Justin M; Brouwer, Ari R; Gessay, Shawn A

    2016-09-01

    In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day-old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state-dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease.

  13. Sensitivity analysis of a sediment dynamics model applied in a Mediterranean river basin: global change and management implications.

    PubMed

    Sánchez-Canales, M; López-Benito, A; Acuña, V; Ziv, G; Hamel, P; Chaplin-Kramer, R; Elorza, F J

    2015-01-01

    Climate change and land-use change are major factors influencing sediment dynamics. Models can be used to better understand sediment production and retention by the landscape, although their interpretation is limited by large uncertainties, including model parameter uncertainties. The uncertainties related to parameter selection may be significant and need to be quantified to improve model interpretation for watershed management. In this study, we performed a sensitivity analysis of the InVEST (Integrated Valuation of Environmental Services and Tradeoffs) sediment retention model in order to determine which model parameters had the greatest influence on model outputs, and therefore require special attention during calibration. The estimation of the sediment loads in this model is based on the Universal Soil Loss Equation (USLE). The sensitivity analysis was performed in the Llobregat basin (NE Iberian Peninsula) for exported and retained sediment, which support two different ecosystem service benefits (avoided reservoir sedimentation and improved water quality). Our analysis identified the model parameters related to the natural environment as the most influential for sediment export and retention. Accordingly, small changes in variables such as the magnitude and frequency of extreme rainfall events could cause major changes in sediment dynamics, demonstrating the sensitivity of these dynamics to climate change in Mediterranean basins. Parameters directly related to human activities and decisions (such as cover management factor, C) were also influential, especially for sediment exported. The importance of these human-related parameters in the sediment export process suggests that mitigation measures have the potential to at least partially ameliorate climate-change driven changes in sediment exportation. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Predictors of attrition from care at 2 years in a prospective cohort of HIV-infected adults in Tigray, Ethiopia

    PubMed Central

    Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Fucili, Luca; Gregorio, Massimiliano Di; Mirra, Marco; Castro, Paola De; Terlizzi, Roberta; Tatarelli, Paola; Binelli, Andrea; Zegeye, Teame; Campagnoli, Michela; Vella, Stefano; Abraham, Loko; Godefay, Hagos

    2017-01-01

    Introduction Ethiopia has experienced rapid expansion of antiretroviral therapy (ART). However, as long-term retention in ART therapy is key for ART effectiveness, determinants of attrition need to be identified so appropriate interventions can be designed. Methods We used data from the ‘Cohort of African people Starting Antiretroviral therapy’ (CASA) project, a prospective study of a cohort of HIV-infected patients who started ART in seven health facilities (HFs). We analysed the data of patients who had started first-line ART between January 2013 and December 2014. The Kaplan–Meier method was used to estimate the probability of retention at different time points. The Cox proportional hazards model was used to identify factors associated with attrition. Results A total of 1198 patients were included in the study. Kaplan–Meier estimates of retention in care were 83.9%, 82.1% and 79.8% at 12, 18 and 24 months after starting ART, respectively. Attrition was mainly due to loss to follow-up, transferred-out patients and documented mortality. A multivariate Cox proportional hazard model showed that male sex, CD4 count <200 cells/µL and the type of HF were significantly associated with attrition. Conclusions The observed attrition differences according to gender suggest that separate interventions designed for women and men should be explored. Moreover, innovative strategies to increase HIV testing should be supported to avoid CD4 levels falling too low, a factor significantly associated with higher attrition in our study. Finally, specific studies to analyse the reasons for different levels of attrition among HFs are required. PMID:29082011

  15. Using an ecosystem service decision support tool to support ridge to reef management: An example of sediment reduction in west Maui, Hawaii

    NASA Astrophysics Data System (ADS)

    Falinski, K. A.; Oleson, K.; Htun, H.; Kappel, C.; Lecky, J.; Rowe, C.; Selkoe, K.; White, C.

    2016-12-01

    Faced with anthropogenic stressors and declining coral reef states, managers concerned with restoration and resilience of coral reefs are increasingly recognizing the need to take a ridge-to-reef, ecosystem-based approach. An ecosystem services framing can help managers move towards these goals, helping to illustrate trade-offs and opportunities of management actions in terms of their impacts on society. We describe a research program building a spatial ecosystem services-based decision-support tool, and being applied to guide ridge-to-reef management in a NOAA priority site in West Maui. We use multiple modeling methods to link biophysical processes to ecosystem services and their spatial flows and social values in an integrating platform. Modeled services include water availability, sediment retention, nutrient retention and carbon sequestration on land. A coral reef ecosystem service model is under development to capture the linkages between terrestrial and coastal ecosystem services. Valuation studies are underway to quantify the implications for human well-being. The tool integrates techniques from decision science to facilitate decision making. We use the sediment retention model to illustrate the types of analyses the tool can support. The case study explores the tradeoffs between road rehabilitation costs and sediment export avoided. We couple the sediment and cost models with trade-off analysis to identify optimal distributed solutions that are most cost-effective in reducing erosion, and then use those models to estimate sediment exposure to coral reefs. We find that cooperation between land owners reveals opportunities for maximizing the benefits of fixing roads and minimizes costs. This research forms the building blocks of an ecosystem service decision support tool that we intend to continue to test and apply in other Pacific Island settings.

  16. How should gestational weight gain be assessed? A comparison of existing methods and a novel method, area under the weight gain curve

    PubMed Central

    Kleinman, Ken P; Oken, Emily; Radesky, Jenny S; Rich-Edwards, Janet W; Peterson, Karen E; Gillman, Matthew W

    2007-01-01

    Background Gestational weight gain is important to assess for epidemiological and public health purposes: it is correlated with infant growth and may be related to maternal outcomes such as reproductive health and chronic disease risk. Methods commonly used to assess weight gain incorporate assumptions that are usually not borne out, such as a linear weight gain, or do not account for differential length of gestation. Methods We introduce a novel method to assess gestational weight gain, the area under the weight gain curve. This is easily interpretable as the additional pound-days carried due to pregnancy and avoids many flaws in alternative assessments. We compare the performance of the simple difference, weekly gain, Institute of Medicine categories and the area under the weight gain curve in predicting birthweight and maternal weight retention at 6, 12, 24 and 36 months post-partum. The analytic sample comprises 2016 participants in Project Viva, an observational prospective cohort study of pregnant women in Massachusetts. Results For birthweight outcomes, none of the weight gain measures is a meaningfully superior predictor. For 6-month postpartum weight retention the simple difference is superior, while for 12-, 24- and 36-month weight retention the area under the weight gain curve is superior. Conclusions These findings are plausible biologically: the same amount of weight gained early vs later in the pregnancy may reflect increased maternal fat stores. The timing of weight gain is reflected best in the area under the weight gain curve. Different methods of measuring gestational weight gain may be appropriate depending on the context. PMID:17715174

  17. Nootropic activity of Albizzia lebbeck in mice.

    PubMed

    Chintawar, S D; Somani, R S; Kasture, Veena S; Kasture, S B

    2002-08-01

    The effect of saponin containing n-butanolic fraction (BF) extracted from dried leaves of Albizzia lebbeck on learning and memory was studied in albino mice using passive shock avoidance paradigm and the elevated plus maze. Significant improvement was observed in the retention ability of the normal and amnesic mice as compared to their respective controls. We have also studied the effects of BF on the behavior influenced by serotonin (5-HT), noradrenaline and dopamine. The brain levels of serotonin, gamma-aminobutyric acid (GABA) and dopamine were also estimated to correlate the behavior with neurotransmitter levels. The brain concentrations of GABA and dopamine were decreased, whereas the 5-HT level was increased. The data indicate the involvement of monoamine neurotransmitters in the nootropic action of BF of A. lebbeck.

  18. Peri-operative physiotherapy.

    PubMed

    Makhabah, Dewi Nurul; Martino, Federica; Ambrosino, Nicolino

    2013-01-23

    Postoperative pulmonary complications (PPC) are a major cause of morbidity, mortality, prolonged hospital stay, and increased cost of care. Physiotherapy (PT) programs in post-surgical and critical area patients are aimed to reduce the risks of PPC due to long-term bed-rest, to improve the patient's quality of life and residual function, and to avoid new hospitalizations. At this purpose, PT programs apply advanced cost-effective therapeutic modalities to decrease complications and patient's ventilator-dependency. Strategies to reduce PPC include monitoring and reduction of risk factors, improving preoperative status, patient education, smoking cessation, intra-operative and postoperative pulmonary care. Different PT techniques, as a part of the comprehensive management of patients undergoing cardiac, upper abdominal, and thoracic surgery, may prevent and treat PPC such as secretion retention, atelectasis, and pneumonia.

  19. Interacting Cache memories: evidence for flexible memory use by Western Scrub-Jays (Aphelocoma californica).

    PubMed

    Clayton, Nicola S; Yu, Kara Shirley; Dickinson, Anthony

    2003-01-01

    When Western Scrub-Jays (Aphelocoma californica) cached and recovered perishable crickets, N. S. Clayton, K. S. Yu, and A. Dickinson (2001) reported that the jays rapidly learned to search for fresh crickets after a 1-day retention interval (RI) between caching and recovery but to avoid searching for perished crickets after a 4-day RI. In the present experiments, the jays generalized their search preference for crickets to intermediate RIs and used novel information about the rate of decay of crickets presented during the RI to reverse these search preferences at recovery. The authors interpret this reversal as evidence that the birds can integrate information about the caching episode with new information presented during the RI.

  20. Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.

    PubMed

    Pan, Hong-Zhen; Chen, Hwei-Hsien

    2007-03-01

    The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs. The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory. Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared. Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats. These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.

  1. Effect of Mimosa pudica (Linn.) extract on anxiety behaviour and GABAergic regulation of 5-HT neuronal activity in the mouse.

    PubMed

    Ayissi Mbomo, Rigobert; Gartside, Sasha; Ngo Bum, Elizabeth; Njikam, Njifutie; Okello, Ed; McQuade, Richard

    2012-04-01

    Mimosa pudica (Linn.) (M. pudica L.) is a plant used in some countries to treat anxiety and depression. In the present study we investigated the effects of an aqueous extract of M. pudica L. on mouse anxiety-like behaviour using the elevated T maze, and on regulation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neuronal activity using an in-vitro mouse brain slice preparation. Acute treatment with M. pudica L. extract had an anxiolytic effect on behaviour in the elevated T maze, specifically on inhibitory avoidance behaviour. Acute application of the extract alone had no effect on the activity of DRN 5-HT neurones. However, when co-applied with the GABA(A) receptor agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), the extract enhanced the inhibitory effect of the THIP on DRN 5-HT neurones. These observed effects of M. pudica L. on both behaviour and GABA modulation of 5-HT neuronal activity are similar to the effects of diazepam, the established anxiolytic and positive modulator of the GABA(A) receptor. This study suggests that the aqueous extract of M. pudica L. contains a positive modulator of GABA(A) receptor function and provides impetus for further investigation of the neuropharmacologically active constituents of the extract.

  2. Effects of cell penetrating Notch inhibitory peptide conjugated to elastin-like polypeptide on glioblastoma cells.

    PubMed

    Opačak-Bernardi, Teuta; Ryu, Jung Su; Raucher, Drazen

    2017-07-01

    Notch pathway was found to be activated in most glioblastomas (GBMs), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia. This complex was further modified with the addition of a cell penetrating peptide, SynB1, for improved cellular uptake and blood-brain barrier penetration. The SynB1-ELP1-dnMAML was examined for its cellular uptake, cytotoxicity, apoptosis, cell cycle inhibition and the inhibition of target genes' expression. SynB1-ELP1-dnMAML inhibited the growth of D54 and U251 cells by inducing apoptosis and cell cycle arrest, especially in the presence of hyperthermia. Hyperthermia increased overall uptake of the polypeptide by the cells and enhanced the resulting pharmacological effects of dnMAML, showing the inhibition of targets of Notch pathway such as Hes-1 and Hey-L. These results confirm that dnMAML is an effective Notch inhibitor and combination with ELP may allow thermal targeting of the SynB1-ELP1-dnMAML complex in cancer cells while avoiding the dangers of systemic Notch inhibition.

  3. Resin-bonded restorations: a strategy for managing anterior tooth loss in adolescence.

    PubMed

    Zitzmann, Nicola U; Özcan, Mutlu; Scherrer, Susanne S; Bühler, Julia M; Weiger, Roland; Krastl, Gabriel

    2015-04-01

    In children or adolescents with anterior tooth loss, space closure with the patient's own teeth should be considered as the first choice to avoid lifelong restorative needs. Thorough diagnostics and treatment planning are required when autotransplantation or orthodontic space closure is considered. If these options are not indicated and a single tooth implant restoration is considered, implant placement should be postponed until adulthood, particularly in young women and in patients with hyperdivergent skeletal growth pattern. A ceramic resin-bonded fixed dental prosthesis with 1 retainer is an excellent treatment solution for the interim period; it may also serve as a long-term restoration, providing that sound enamel structure is present, sufficient framework dimensions have been provided, adhesive cementation techniques have been meticulously applied, and functional contacts of the cantilever pontic avoided. In contrast, a resin-bonded fixed dental prosthesis with a metal framework and retentive preparation is indicated if the palatal enamel structure is compromised, interocclusal clearance is limited, splinting (such as after orthodontic treatment) is required, or more than 1 tooth has to be replaced. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  4. Cognitive benefits of Angiotensin IV and Angiotensin-(1-7): a systematic review of experimental studies.

    PubMed

    Ho, Jean K; Nation, Daniel A

    2018-05-04

    To explore effects of the brain renin-angiotensin system (RAS) on cognition. Systematic review of experimental (non-human) studies assessing cognitive effects of RAS peptides angiotensin-(3-8) [Ang IV] and angiotensin-(1-7) [Ang-(1-7)] and their receptors, the Ang IV receptor (AT4R) and the Mas receptor. Of 450 articles identified, 32 met inclusion criteria. Seven of 11 studies of normal animals found Ang IV had beneficial effects on tests of passive or conditioned avoidance and object recognition. In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle 1 -Ang IV, dihexa, LVV-hemorphin-7) improved performance on spatial working memory and passive avoidance tasks. Two of three studies examining Ang-(1-7) found it benefited memory. Mas receptor removal was associated with reduced fear memory in one study. Studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, as well as AT4R activation. Brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing. Ang-(1-7) shows anti-dementia qualities. Copyright © 2018. Published by Elsevier Ltd.

  5. Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms.

    PubMed

    Ghofrani, Saeed; Joghataei, Mohammad-Taghi; Mohseni, Simin; Baluchnejadmojarad, Tourandokht; Bagheri, Maryam; Khamse, Safoura; Roghani, Mehrdad

    2015-10-05

    Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Aβ) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Aβ-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulvestrant (an estrogenic receptor antagonist) significantly improved the performance of Aβ-injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Aβ-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Aβ-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Calculation of energy recovery and greenhouse gas emission reduction from palm oil mill effluent treatment by an anaerobic granular-sludge process.

    PubMed

    Show, K Y; Ng, C A; Faiza, A R; Wong, L P; Wong, L Y

    2011-01-01

    Conventional aerobic and low-rate anaerobic processes such as pond and open-tank systems have been widely used in wastewater treatment. In order to improve treatment efficacy and to avoid greenhouse gas emissions, conventional treatment can be upgraded to a high performance anaerobic granular-sludge system. The anaerobic granular-sludge systems are designed to capture the biogas produced, rendering a potential for claims of carbon credits under the Kyoto Protocol for reducing emissions of greenhouse gases. Certified Emission Reductions (CERs) would be issued, which can be exchanged between businesses or bought and sold in international markets at the prevailing market prices. As the advanced anaerobic granular systems are capable of handling high organic loadings concomitant with high strength wastewater and short hydraulic retention time, they render more carbon credits than other conventional anaerobic systems. In addition to efficient waste degradation, the carbon credits can be used to generate revenue and to finance the project. This paper presents a scenario on emission avoidance based on a methane recovery and utilization project. An example analysis on emission reduction and an overview of the global emission market are also outlined.

  7. Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

    PubMed

    Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

    2010-08-01

    Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

  8. Safe percutaneous suprapubic catheterisation

    PubMed Central

    Goyal, NK; Goel, A; Sankhwar, SN

    2012-01-01

    INTRODUCTION We describe our technique of percutaneous suprapubic catheter insertion with special reference to steps that help to avoid common complications of haematuria and catheter misplacement. METHODS The procedure is performed using a stainless steel reusable trocar under local infiltrative anaesthesia, usually at the bedside. After clinical confirmation of a full bladder, the trocar is advanced into the bladder through a skin incision. Once the bladder is entered, the obturator is removed and the assistant inserts a Foley catheter followed by rapid balloon inflation. Slight traction is applied to the catheter for about five minutes. Patients with previous lower abdominal surgery, an inadequately distended bladder or acute pelvic trauma do not undergo suprapubic catheterisation using this method. RESULTS The procedure was performed in 72 men (mean age: 42.4 years, range: 18–78 years) with urinary retention with a palpable bladder. The average duration of the procedure was less than five minutes. No complications were noted in any of the patients. CONCLUSIONS Trocar suprapubic catheter insertion is a safe and effective bedside procedure for emergency bladder drainage and can be performed by resident surgeons. The common complications associated with the procedure can be avoided with a few careful steps. PMID:23131233

  9. Gradual training reduces practice difficulty while preserving motor learning of a novel locomotor task.

    PubMed

    Sawers, Andrew; Hahn, Michael E

    2013-08-01

    Motor learning strategies that increase practice difficulty and the size of movement errors are thought to facilitate motor learning. In contrast to this, gradual training minimizes movement errors and reduces practice difficulty by incrementally introducing task requirements, yet remains as effective as sudden training and its large movement errors for learning novel reaching tasks. While attractive as a locomotor rehabilitation strategy, it remains unknown whether the efficacy of gradual training extends to learning locomotor tasks and their unique requirements. The influence of gradual vs. sudden training on learning a locomotor task, asymmetric split belt treadmill walking, was examined by assessing whole body sagittal plane kinematics during 24 hour retention and transfer performance following either gradual or sudden training. Despite less difficult and less specific practice for the gradual cohort on day 1, gradual training resulted in equivalent motor learning of the novel locomotor task as sudden training when assessed by retention and transfer a day later. This suggests that large movement errors and increased practice difficulty may not be necessary for learning novel locomotor tasks. Further, gradual training may present a viable locomotor rehabilitation strategy avoiding large movement errors that could limit or impair improvements in locomotor performance. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. In-Vessel Tritium Retention and Removal in ITER-FEAT

    NASA Astrophysics Data System (ADS)

    Federici, G.; Brooks, J. N.; Iseli, M.; Wu, C. H.

    Erosion of the divertor and first-wall plasma-facing components, tritium uptake in the re-deposited films, and direct implantation in the armour material surfaces surrounding the plasma, represent crucial physical issues that affect the design of future fusion devices. In this paper we present the derivation, and discuss the results, of current predictions of tritium inventory in ITER-FEAT due to co-deposition and implantation and their attendant uncertainties. The current armour materials proposed for ITER-FEAT are beryllium on the first-wall, carbon-fibre-composites on the divertor plate near the separatrix strike points, to withstand the high thermal loads expected during off-normal events, e.g., disruptions, and tungsten elsewhere in the divertor. Tritium co-deposition with chemically eroded carbon in the divertor, and possibly with some Be eroded from the first-wall, is expected to represent the dominant mechanism of in-vessel tritium retention in ITER-FEAT. This demands efficient in-situ methods of mitigation and retrieval to avoid frequent outages due to the reaching of precautionary operating limits set by safety considerations (e.g., ˜350 g of in-vessel co-deposited tritium) and for fuel economy reasons. Priority areas where further R&D work is required to narrow the remaining uncertainties are also briefly discussed.

  11. Oculomotor selection underlies feature retention in visual working memory.

    PubMed

    Hanning, Nina M; Jonikaitis, Donatas; Deubel, Heiner; Szinte, Martin

    2016-02-01

    Oculomotor selection, spatial task relevance, and visual working memory (WM) are described as three processes highly intertwined and sustained by similar cortical structures. However, because task-relevant locations always constitute potential saccade targets, no study so far has been able to distinguish between oculomotor selection and spatial task relevance. We designed an experiment that allowed us to dissociate in humans the contribution of task relevance, oculomotor selection, and oculomotor execution to the retention of feature representations in WM. We report that task relevance and oculomotor selection lead to dissociable effects on feature WM maintenance. In a first task, in which an object's location was encoded as a saccade target, its feature representations were successfully maintained in WM, whereas they declined at nonsaccade target locations. Likewise, we observed a similar WM benefit at the target of saccades that were prepared but never executed. In a second task, when an object's location was marked as task relevant but constituted a nonsaccade target (a location to avoid), feature representations maintained at that location did not benefit. Combined, our results demonstrate that oculomotor selection is consistently associated with WM, whereas task relevance is not. This provides evidence for an overlapping circuitry serving saccade target selection and feature-based WM that can be dissociated from processes encoding task-relevant locations. Copyright © 2016 the American Physiological Society.

  12. Reaching everyone: Promoting the inclusion of youth with disabilities in evaluating foster care outcomes

    PubMed Central

    Blakeslee, Jennifer E.; Quest, A. Del; Powers, Jennifer; Powers, Laurie E.; Geenen, Sarah; Nelson, May; Dalton, Lawrence D.; McHugh, Elizabeth

    2013-01-01

    Efforts to evaluate foster care outcomes must avoid systematic exclusion of particular groups. Although often unrecognized as such, youth with disabilities are highly overrepresented in the U.S. foster care system, and yet youth with some disabilities, including those with intellectual, serious emotional, and physical impairments may be underrepresented in research and evaluation studies evaluating foster care outcomes. The recruitment and retention of youth with various disabilities in such studies can be impeded by under-identification of disability and relatively high placement and school mobility. Furthermore, youth with various disabilities may experience more disappointing outcomes than foster youth overall, underscoring the importance of including these youth in outcome tracking efforts. This is especially relevant given the recent implementation of the National Youth in Transition Database (NYTD), which requires that state child welfare agencies gather baseline information about youth in foster care at age 17, and then survey outcomes at 19 and 21. To promote the full participation of foster youth with disabilities in such outcome evaluation, this paper describes successful strategies for identifying and retaining participants that were used in three separate longitudinal intervention studies. These strategies include the systematic recruitment of foster youth by special education status, and creative use of validated tracking and retention strategies incorporating minor accommodations as needed. PMID:24273364

  13. Cognitive aid for neonatal resuscitation: a prospective single-blinded randomized controlled trial.

    PubMed

    Bould, M D; Hayter, M A; Campbell, D M; Chandra, D B; Joo, H S; Naik, V N

    2009-10-01

    Retention of skills and knowledge after neonatal resuscitation courses (NRP) is known to be problematic. The use of cognitive aids is mandatory in industries such as aviation, to avoid dependence on memory when decision-making in critical situations. We aimed to prospectively investigate the effect of a cognitive aid on the performance of simulated neonatal resuscitation. Thirty-two anaesthesia residents were recruited. The intervention group had a poster detailing the NRP algorithm and the control group did not. Video recordings of each of the performances were analysed using a previously validated checklist by a peer, an expert anaesthetist, and an expert neonatologist. The median (IQR) checklist score in the control group [18.2 (15.0-20.5)] was not significantly different from that in the intervention group [20.3 (18.3-21.3)] (P=0.08). When evaluated by the neonatologist, none of the subjects correctly performed all life-saving interventions necessary to pass the checklist. A minority of the intervention group used the cognitive aid frequently. Retention of skills after NRP training is poor. The infrequent use of the cognitive aid may be the reason that it did not improve performance. Further research is required to investigate whether cognitive aids can be useful if their use is incorporated into the NRP training.

  14. Patient-related risk factors for urinary retention following ambulatory general surgery: a systematic review and meta-analysis.

    PubMed

    Mason, Sam E; Scott, Alasdair J; Mayer, Erik; Purkayastha, Sanjay

    2016-06-01

    Postoperative urinary retention (POUR) is a source of avoidable patient harm. The aim of this review is to identify and quantify the role of patient-related risk factors in the development of POUR following ambulatory general surgery. Studies published until December 2014 were identified by searching MEDLINE, EMBASE, and PsycINFO databases. Risk factors assessed in 3 or more studies were meta-analyzed. Twenty-one studies were suitable for inclusion consisting of 7,802 patients. The incidence of POUR was 14%. Increased age and the presence of lower urinary tract symptoms significantly increased risk with odds ratios [ORs] of 2.11 (95% confidence interval [CI] 1.15 to 3.86) and 2.83 (1.57 to 5.08), respectively. Male sex was not associated with developing POUR (OR .96, 95% CI .62 to 1.50). Preoperative α-blocker use significantly decreased the incidence of POUR with an OR of .37 (95% CI .15 to .91). Increased age and the presence of lower urinary tract symptoms increase the risk of POUR, while α-blocker use confers protection. Male sex was not associated with POUR. These findings assist in preoperative identification of patients at high risk of POUR. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Comparison of mercury retention by fly ashes using different experimental devices

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lopez-Anton, M.A.; Abad-Valle, P.; Diaz-Somoano, M.

    2009-12-15

    To study mercury (Hg) retention in solid sorbents, researchers generally employ similar laboratory-scale devices. However, despite their similarities, these devices are generally used under different experimental conditions. The Hg concentration in the gas phase, gas flow, and sorbent-bed characteristics are variables that influence the contact time, mass transfer, and kinetics and may greatly modify the quantities of Hg retained when the same sorbents are compared. These differences in the experimental conditions do not impede an evaluation of the sorbents as long as the results obtained points toward the same qualitative conclusions. However, the extent of variation needs to be definedmore » to avoid misinterpretation. To illustrate the range of interpretations, the results of a preliminary approach using four experimental devices in two laboratories have been compared in this work. All the experiments were carried out under a nitrogen atmosphere and Hg{sup 0} in the gas phase. The same sorbents were employed in all the devices. These were fly ashes obtained from the combustion of coals of different rank and with different unburned carbon contents. From the results obtained it can be inferred that it is necessary to strictly control the influence of the experimental variables to infer a correct interpretation of the results.« less

  16. Enhancing MRI of liver metastases with a zwitterionized biodegradable dendritic contrast agent.

    PubMed

    Zhou, Xiaoxuan; Ye, Mingzhou; Han, Yuxin; Tang, Jianbin; Qian, Yue; Hu, Hongjie; Shen, Youqing

    2017-07-25

    Metastasis is the main reason for cancer-associated mortality, and accurate diagnostic imaging of metastases is critical for the clinical administration and tailoring personalized treatments for metastatic tumors. However, magnetic resonance imaging of metastases in the liver is impeded by its low sensitivity because the currently used contrast agents accumulate in hepatocytes and Kupffer cells instead of cancer cells. Herein, a 4 th generation zwitterionized biodegradable dendritic contrast agent (DCA) with a size of ca. 9 nm and a longitudinal relaxivity of 15.7 mM -1 s -1 in terms of Gd was synthesized and used to enhance the MRI of liver metastasis. The DCA could remarkably enhance the MRI of metastasized tumors in the liver, because it could simultaneously reduce the background signal in the liver by avoiding uptake by hepatocytes and Kupffer cells through the zwitterionization and increase the signal in tumors through the enhanced permeability and retention effect. Moreover, in contrast to non-biodegradable DCA, this DCA showed minimal long-term Gd 3+ retention in all organs and tissues because it could be degraded into small fragments. The significant capability of enhancing the MRI of metastases in the liver plus its excellent biodegradability made this DCA a promising CA for metastatic tumor imaging.

  17. Complications and salvage options after laser lithotripsy for a vesical calculus in a tetraplegic patient: a case report.

    PubMed

    Vaidyanathan, Subramanian; Singh, Gurpreet; Selmi, Fahed; Hughes, Peter L; Soni, Bakul M; Oo, Tun

    2015-01-01

    Laser lithotripsy of vesical calculi in tetraplegic subjects with long-term urinary catheters is fraught with complications because of bladder wall oedema, infection, fragile urothelium, bladder spasms, and autonomic dysreflexia. Severe haematuria should be anticipated; failure to institute measures to minimise bleeding and prevent clot retention can be catastrophic. We present an illustrative case. A tetraplegic patient underwent laser lithotripsy of vesical stone under general anaesthesia. During lithotripsy, severe bladder spasms and consequent rise in blood pressure occurred. Bleeding continued post-operatively resulting in clot retention. CT revealed clots within distended but intact bladder. Clots were sucked out and continuous bladder irrigation was commenced. Bleeding persisted; patient developed repeated clot retention. Cystoscopy was performed to remove clots. Patient developed abdominal distension. Bladder rupture was suspected; bed-side ultrasound scan revealed diffuse small bowel dilatation with mild peritoneal effusion; under-filled bladder containing small clot. Patient developed massive abdominal distension and ileus. Two days later, CT with oral positive contrast revealed intra-peritoneal haematoma at the dome of bladder with perforation at the site of haematoma. Free fluid was noted within the peritoneal cavity. This patient was managed by gastric drainage and intravenous fluids. Patient's condition improved gradually with urethral catheter drainage. Follow-up CT revealed resolution of bladder rupture, perivesical haematoma, and intra-peritoneal free fluid. If bleeding occurs, bladder irrigation should be commenced immediately after surgery to prevent clot retention. When bladder rupture is suspected, CT of abdomen should be done instead of ultrasound scan, which may not reveal bladder perforation. It is debatable whether laparotomy and repair of bladder rupture is preferable to nonoperative management in tetraplegics. Anti-muscarinic drugs should be prescribed prior to lithotripsy to control bladder spasms; aspirin and ibuprofen should be omitted. If significant bleeding occurs during lithotripsy, procedure should be stopped and rescheduled. Percutaneous cystolithotripsy using a wide channel could be quicker to clear stones, as larger fragments could be retrieved; lesser stimulant for triggering autonomic dysreflexia, as it avoids urethral manipulation. But in patients with small, contracted bladder, and protuberant abdomen, percutaneous access to urinary bladder may be difficult and can result in injury to bowels.

  18. Conjugated linoleic acid-enriched butter improved memory and up-regulated phospholipase A2 encoding-genes in rat brain tissue.

    PubMed

    Gama, Marco A S; Raposo, Nádia R B; Mury, Fábio B; Lopes, Fernando C F; Dias-Neto, Emmanuel; Talib, Leda L; Gattaz, Wagner F

    2015-10-01

    Reduced phospholipase A2 (PLA2) activity has been reported in blood cells and in postmortem brains of patients with Alzheimer disease (AD), and there is evidence that conjugated linoleic acid (CLA) modulates the activity of PLA2 groups in non-brain tissues. As CLA isomers were shown to be actively incorporated and metabolized in the brains of rats, we hypothesized that feeding a diet naturally enriched in CLA would affect the activity and expression of Pla 2 -encoding genes in rat brain tissue, with possible implications for memory. To test this hypothesis, Wistar rats were trained for the inhibitory avoidance task and fed a commercial diet (control) or experimental diets containing either low CLA- or CLA-enriched butter for 4 weeks. After this period, the rats were tested for memory retrieval and killed for tissue collection. Hippocampal expression of 19 Pla 2 genes was evaluated by qPCR, and activities of PLA2 groups (cPLA2, iPLA2, and sPLA2) were determined by radioenzymatic assay. Rats fed the high CLA diet had increased hippocampal mRNA levels for specific PLA2 isoforms (iPla 2 g6γ; cPla 2 g4a, sPla 2 g3, sPla 2 g1b, and sPla 2 g12a) and higher enzymatic activity of all PLA2 groups as compared to those fed the control and the low CLA diet. The increment in PLA2 activities correlated significantly with memory enhancement, as assessed by increased latency in the step-down inhibitory avoidance task after 4 weeks of treatment (rs = 0.69 for iPLA2, P < 0.001; rs = 0.81 for cPLA2, P < 0.001; and rs = 0.69 for sPLA2, P < 0.001). In face of the previous reports showing reduced PLA2 activity in AD brains, the present findings suggest that dairy products enriched in cis-9, trans-11 CLA may be useful in the treatment of this disease.

  19. Constructive and Unproductive Processing of Traumatic Experiences in Trauma-Focused Cognitive-Behavioral Therapy for Youth.

    PubMed

    Hayes, Adele M; Yasinski, Carly; Grasso, Damion; Ready, C Beth; Alpert, Elizabeth; McCauley, Thomas; Webb, Charles; Deblinger, Esther

    2017-03-01

    Although there is substantial evidence to support the efficacy of cognitive-behavioral treatments (CBT) for posttraumatic stress disorder (PTSD), there is some debate about how these treatments have their effects. Modern learning theory and cognitive and emotional processing theories highlight the importance of reducing avoidance, facilitating the constructive processing of feared experiences, and strengthening new inhibitory learning. We examined variables thought to be associated with unproductive and constructive processing of traumatic experiences in a sample of 81 youth with elevated PTSD symptoms, who received Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for abuse or traumatic interpersonal loss. Sessions during the trauma narrative phase of TF-CBT were coded for indicators of unproductive processing (overgeneralization, rumination, avoidance) and constructive processing (decentering, accommodation of corrective information), as well as levels of negative emotion. In previous analyses of this trial (Ready et al., 2015), more overgeneralization during the narrative phase predicted less improvement in internalizing symptoms at posttreatment and a worsening of externalizing symptoms over the 12-month follow-up. In contrast, more accommodation predicted improvement in internalizing symptoms and also moderated the negative effects of overgeneralization on internalizing and externalizing symptoms. The current study examined correlates of overgeneralization and accommodation. Overgeneralization was associated with more rumination, less decentering, and more negative emotion, suggesting immersion in trauma-related material. Accommodation was associated with less avoidance and more decentering, suggesting a healthy distance from trauma-related material that might allow for processing and cognitive change. Decentering also predicted improvement in externalizing symptoms at posttreatment. Rumination and avoidance showed important associations with overgeneralization and accommodation, respectively, but did not predict treatment outcomes. This study identifies correlates of overgeneralization and accommodation that might shed light on how these variables relate to unproductive and constructive processing of traumatic experiences. Copyright © 2016. Published by Elsevier Ltd.

  20. A Burkholderia sacchari cell factory: production of poly-3-hydroxybutyrate, xylitol and xylonic acid from xylose-rich sugar mixtures.

    PubMed

    Raposo, Rodrigo S; de Almeida, M Catarina M D; de Oliveira, M da Conceição M A; da Fonseca, M Manuela; Cesário, M Teresa

    2017-01-25

    Efficient production of poly-3-hydroxybutyrate (P(3HB)) based on glucose-xylose mixtures simulating different types of lignocellulosic hydrolysate (LCH) was addressed using Burkholderia sacchari, a wild strain capable of metabolizing both sugars and producing P(3HB). Carbon catabolite repression was avoided by maintaining glucose concentration below 10g/L. Xylose concentrations above 30g/L were inhibitory for growth and production. In fed-batch cultivations, pulse size and feed addition rate were controlled in order to reach high productivities and efficient sugar consumptions. High xylose uptake and P(3HB) productivity were attained with glucose-rich mixtures (glucose/xylose ratio in the feed=1.5w/w) using high feeding rates, while with xylose-richer feeds (glucose/xylose=0.8w/w), a lower feeding rate is a robust strategy to avoid xylose build-up in the medium. Xylitol production was observed with xylose concentrations in the medium above 30-40g/L. With sugar mixtures featuring even lower glucose/xylose ratios, i.e. xylose-richer feeds (glucose/xylose=0.5), xylonic acid (a second byproduct) was produced. This is the first report of the ability of Burkholderia sacchari to produce both xylitol and xylonic acid. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Intrahippocampal administration of an antibody against the HNK-1 carbohydrate impairs memory consolidation in an inhibitory learning task in mice.

    PubMed

    Strekalova, T; Wotjak, C T; Schachner, M

    2001-06-01

    Many cell adhesion molecules express the HNK-1 carbohydrate involved in formation and functioning of synapses. To assess its role in learning, we injected the monoclonal HNK-1 antibody or nonimmune IgG into the hippocampus of C57BL/6J mice 1 h after training in a step-down avoidance task. In animals treated with the HNK-1 antibody, latencies of step down in a recall session 48 h after injection did not change compared to training values and were significantly shorter versus IgG-treated controls, which acquired the task normally. Similar differences between the two treatments were also observed after a stronger training protocol in a step-down avoidance paradigm. The HNK-1 antibody was effective only when injected 1 h, but not 48 h after training, thus affecting memory consolidation but not memory recall itself. The HNK-1 antibody impaired memory also in tenascin-R knock-out mice, indicating that extracellular matrix molecule tenascin-R, one of the carriers of the HNK-1epitope in the hippocampus, does not mediate the function of the HNK-1 carbohydrate in this task. Our observations show that the HNK-1 carbohydrate is critically involved in memory consolidation in hippocampus-dependent learning in mammals. Copyright 2001 Academic Press.

  2. Ontogeny of passive avoidance learning in domestic chicks: punishment of key-peck and running responses.

    PubMed

    Mattingly, B A; Zolman, J F

    1980-08-01

    The effect of the number of prepunishment acquisition trials on the age dependency of passive avoidance (PA) learning of the Vantress X Arbor Acre chick was determined in both key-peck and runway tests. In nine experiments, 1- and 4-day-old chicks were first trained to respond for heat reward, and then, following a variable number of reinforced acquisition trials, the chicks' responses were punished with aversive wing shocks. The major finding of these experiments was that the age dependency of PA learning of the young chick is related specifically to the number of reinforced training trials given prior to PA testing. When a large number of prepunishment acquisition trials were given, 1-day-old chicks learned as quickly as 4-day-old chicks to withhold responding when punished. However, when only a few acquisition trials preceded PA testing, 1-day-old chicks showed significantly less response suppression than 4-day-old chicks. These acquisition effects indicate that the age-dependent changes in PA learning of the chick are not solely due to developmental changes in general inhibitory ability. Rather, these PA results suggest that the 1-day-old chick, compared with the 4-day-old chick, is deficient in learning, or detecting changes in, stimulus- and/or response-reinforcement contingencies.

  3. Why are people with high self-control happier? The effect of trait self-control on happiness as mediated by regulatory focus

    PubMed Central

    Cheung, Tracy T. L.; Gillebaart, Marleen; Kroese, Floor; De Ridder, Denise

    2014-01-01

    Background: While self-control has often been related to positive outcomes in life such as higher academic achievements and better health, recent insights reveal that people with high trait self-control (TSC) may even experience greater life satisfaction or happiness. Objective: The current study further scrutinizes this potential association between TSC and happiness, and examines how regulatory focus, defined as the way people frame and direct their goal pursuit strategies, plays a role in this relationship. Accordingly, the present study examines the mediating role of regulatory-focus (promotion and prevention focus) on the relationship between TSC and happiness. Method: Data was collected from 545 individuals (65.9% female, Mage = 27.52 years) regarding their TSC, regulatory focus, and happiness. Results: Mediation analyses demonstrate that TSC positively predicts happiness, while this effect was partially mediated by relatively more promotion focus and less prevention focus. Conclusion: Results suggest that people with higher TSC are happier possibly because they are: (1) more promotion-focused on acquiring positive gains thereby facilitating more approach-oriented behaviors, and (2) less prevention-focused on avoiding losses thereby reducing avoidance-oriented behaviors. These findings are relevant for topical scientific debates regarding the underlying mechanisms of self-control regarding initiatory and inhibitory behaviors. PMID:25071683

  4. Camptotheca acuminata 10-hydroxycamptothecin O-methyltransferase: an alkaloid biosynthetic enzyme coopted from flavonoid metabolism.

    PubMed

    Salim, Vonny; Jones, A Daniel; DellaPenna, Dean

    2018-04-22

    The medicinal plant Camptotheca acuminata accumulates camptothecin, 10-hydroxycamptothecin, and 10-methoxycamptothecin as its major bioactive monoterpene indole alkaloids. Here, we describe identification and functional characterization of 10-hydroxycamptothecin O-methyltransferase (Ca10OMT), a member of the Diverse subclade of Class II OMTs. Ca10OMT is highly active toward both its alkaloid substrate and a wide range of flavonoids in vitro and in this way contrasts with other alkaloid OMTs in the subclade that only utilize alkaloid substrates. Ca10OMT shows a strong preference for the A-ring 7-OH of flavonoids, which is structurally equivalent to the 10-OH of 10-hydroxycamptothecin. The substrates of other alkaloid OMTs in the subclade bear little similarity to flavonoids, but the 3-D positioning of the 7-OH, A- and C-rings of flavonoids is nearly identical to the 10-OH, A- and B-rings of 10-hydroxycamptothecin. This structural similarity likely explains the retention of flavonoid OMT activity by Ca10OMT and also why kaempferol and quercetin aglycones are potent inhibitors of its 10-hydroxycamptothecin activity. The catalytic promiscuity and strong inhibition of Ca10OMT by flavonoid aglycones in vitro prompted us to investigate the potential physiological roles of the enzyme in vivo. Based on its regioselectivity, kinetic parameters and absence of 7-OMT flavonoids in vivo, we conclude that the major and likely only substrate of Ca10OMT in vivo is 10-hydroxycamptothecin. This is likely accomplished by Ca10OMT being kept spatially separated at the tissue levels from potentially inhibitory flavonoid aglycones, and flavonoid aglycones being rapidly glycosylated to non-inhibitory flavonoid glycosides. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury

    PubMed Central

    Mondrinos, Mark J.; Knight, Linda C.; Kennedy, Paul A.; Wu, Jichuan; Kauffman, Matthew; Baker, Sandy T.; Wolfson, Marla R.

    2015-01-01

    Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-δ (PKCδ) as a critical regulator of the acute inflammatory response and demonstrated that PKCδ inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCδ is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)–conjugated PKCδ inhibitory peptide (PKCδ-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy. There was negligible lung uptake of radiolabeled peptide upon intravenous delivery [<1% initial dose (ID)], whereas IT administration resulted in lung retention of >65% ID with minimal uptake in liver or kidney (<2% ID). IT delivery of a fluorescent-tagged (tetramethylrhodamine-PKCδ-TAT) peptide demonstrated uniform spatial distribution and cellular uptake throughout the peripheral lung. IT delivery of PKCδ-TAT at the time of CLP surgery significantly reduced PKCδ activation (tyrosine phosphorylation, nuclear translocation and cleavage) and acute lung inflammation, resulting in improved lung function and gas exchange. Importantly, peptide efficacy was similar when delivered at 4 hours post-CLP, demonstrating therapeutic relevance. Conversely, spatial lung distribution and efficacy were significantly impaired at 8 hours post-CLP, which corresponded to marked histopathological progression of lung injury. These studies establish a functional connection between peptide spatial distribution, inflammatory histopathology in the lung, and efficacy of this anti-inflammatory peptide. PMID:26243739

  6. Inhibitory effect on natural killer activity of microphthalmia transcription factor encoded by the mutant mi allele of mice.

    PubMed

    Ito, A; Kataoka, T R; Kim, D K; Koma , Y; Lee, Y M; Kitamura, Y

    2001-04-01

    The mouse mi locus encodes a basic-helix-loop-helix-leucine zipper-type transcription factor, microphthalmia transcription factor (MITF). Mice of mi/mi genotype express a mutant form of MITF (mi-MITF), whereas mice of tg/tg genotype have a transgene in the 5' flanking region of the mi gene and do not express MITF. Although the mi/mi mouse is deficient in natural killer (NK) activity, it was found that the tg/tg mouse was normal in this respect. To know the cause, spleen cells of both genotypes were compared. Although the proportion of spleen cells expressing an NK cell marker, NK1.1, was comparable in both mice, the proportion of large granular lymphocytes decreased only in mi/mi mice. The difference between mi/mi and tg/tg mice was reproducible in the culture supplemented with interleukin-2. Moreover, the perforin gene expression was reduced in mi/mi-cultured spleen cells. Wild-type (+) MITF transactivated, but mi-MITF suppressed, the perforin gene promoter through the NF-P motif, a strong cis-acting element. However, neither +-MITF nor mi-MITF bound the NF-P motif. Instead, 2 nuclear factors that bound the NF-P motif were retained in the cytoplasm of mi/mi-cultured spleen cells. In addition, overexpression of mi-MITF resulted in cytoplasmic retention of the 2 NF-P motif-binding factors in cytotoxic T lymphocytes. The presence of mi-MITF rather than the absence of +-MITF appeared to lead to poor transactivation of the NF-P motif by intercepting NF-P motif-binding factors. This inhibitory effect of mi-MITF may cause the deficient cytotoxicity of NK cells in mi/mi mice. (Blood. 2001;97:2075-2083)

  7. Dichotomous Dynamics in E-I Networks with Strongly and Weakly Intra-connected Inhibitory Neurons

    PubMed Central

    Rich, Scott; Zochowski, Michal; Booth, Victoria

    2017-01-01

    The interconnectivity between excitatory and inhibitory neural networks informs mechanisms by which rhythmic bursts of excitatory activity can be produced in the brain. One such mechanism, Pyramidal Interneuron Network Gamma (PING), relies primarily upon reciprocal connectivity between the excitatory and inhibitory networks, while also including intra-connectivity of inhibitory cells. The causal relationship between excitatory activity and the subsequent burst of inhibitory activity is of paramount importance to the mechanism and has been well studied. However, the role of the intra-connectivity of the inhibitory network, while important for PING, has not been studied in detail, as most analyses of PING simply assume that inhibitory intra-connectivity is strong enough to suppress subsequent firing following the initial inhibitory burst. In this paper we investigate the role that the strength of inhibitory intra-connectivity plays in determining the dynamics of PING-style networks. We show that networks with weak inhibitory intra-connectivity exhibit variations in burst dynamics of both the excitatory and inhibitory cells that are not obtained with strong inhibitory intra-connectivity. Networks with weak inhibitory intra-connectivity exhibit excitatory rhythmic bursts with weak excitatory-to-inhibitory synapses for which classical PING networks would show no rhythmic activity. Additionally, variations in dynamics of these networks as the excitatory-to-inhibitory synaptic weight increases illustrates the important role that consistent pattern formation in the inhibitory cells serves in maintaining organized and periodic excitatory bursts. Finally, motivated by these results and the known diversity of interneurons, we show that a PING-style network with two inhibitory subnetworks, one strongly intra-connected and one weakly intra-connected, exhibits organized and periodic excitatory activity over a larger parameter regime than networks with a homogeneous inhibitory population. Taken together, these results serve to better articulate the role of inhibitory intra-connectivity in generating PING-like rhythms, while also revealing how heterogeneity amongst inhibitory synapses might make such rhythms more robust to a variety of network parameters. PMID:29326558

  8. The threat of male-to-female erotic transference.

    PubMed

    Celenza, Andrea

    2006-01-01

    Vignettes from an ongoing psychoanalysis with a patient, Michael, are presented to illustrate the various dimensions of the erotic transference at different phases of the treatment. The relation to power, the experience and expression of aggression, how these may be organized by gender, and the female analyst's countertransference are discussed as potentially fostering or inhibitory in the development of an erotic transference. Traditional sociocultural gender stereotypes kept alive in fantasy can cause female analysts to subtly foreclose the impending threat of an intense erotic transference with male analysands due to a fear of outwardly directed male aggression. It is suggested that the maternal/containing transference can be unconsciously fostered by both analyst and analysand to defensively avoid expression of the aggressivized erotic transference in its full intensity. Similarities and differences in cases of sexual boundary violations with opposite-gender pairings are discussed.

  9. Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3.

    PubMed

    Nakajima, Yutaka; Aoyama, Naohiro; Takahashi, Fumie; Sasaki, Hiroshi; Hatanaka, Keiko; Moritomo, Ayako; Inami, Masamichi; Ito, Misato; Nakamura, Koji; Nakamori, Fumihiro; Inoue, Takayuki; Shirakami, Shohei

    2016-10-01

    In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The nearest relative in mental health law.

    PubMed

    Andoh, Benjamin; Gogo, Emmanuel

    2004-04-01

    This article considers the concept of the 'nearest relative' in mental health law in England and Wales and argues, inter alia, for its retention in a way that avoids violation of the European Convention on Human Rights and the Human Rights Act 1998. It looks, first, at the meaning of nearest relative and then focuses on his/her role today, including its link with advance directives for mental health care, and on the tension between nearest relatives and approved social workers and the law. The problem exposed by JT v. United Kingdom in relation to the Human Rights Act 1998 and its implications for the future are considered. The impact of the Mental Health Bill (2002) on the nearest relative is discussed and recommendations to improve the present law are then suggested.

  11. Conserving Critical Sites for Biodiversity Provides Disproportionate Benefits to People

    PubMed Central

    Larsen, Frank W.; Turner, Will R.; Brooks, Thomas M.

    2012-01-01

    Protecting natural habitats in priority areas is essential to halt the loss of biodiversity. Yet whether these benefits for biodiversity also yield benefits for human well-being remains controversial. Here we assess the potential human well-being benefits of safeguarding a global network of sites identified as top priorities for the conservation of threatened species. Conserving these sites would yield benefits – in terms of a) climate change mitigation through avoidance of CO2 emissions from deforestation; b) freshwater services to downstream human populations; c) retention of option value; and d) benefits to maintenance of human cultural diversity – significantly exceeding those anticipated from randomly selected sites within the same countries and ecoregions. Results suggest that safeguarding sites important for biodiversity conservation provides substantial benefits to human well-being. PMID:22666337

  12. The "in situ molding technique: " an accurate and simple way to fix resorbable plates to the facial skeleton.

    PubMed

    Sadigh, Parviz Lionel; Chang, Li-Ren; Feng, Kuan-Ming; Jeng, Seng-Feng

    2014-09-01

    Bioabsorbable plates developed for use in the facial skeleton have become an integral part of the craniomaxillofacial surgeon's reconstructive armamentarium. They avoid the problems associated with the retention of metal plates and can be easily contoured when heated in a thermobath. The technical process of molding and securing these devices, often through small access incisions, to achieve rigid fixation of facial fractures can be difficult. In this article, we describe a simple, novel technique that we have developed, using hot water suction irrigation, to achieve in situ molding of resorbable plates during facial fracture fixation. We used this technique to fix 123 facial fractures in 110 patients over a 4-year period. No complications secondary to the use of hot water suction irrigation were encountered.

  13. Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: Implications for diet-induced prefrontal cortex dysregulation.

    PubMed

    Baker, Kathryn D; Reichelt, Amy C

    2016-12-01

    Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet. The HFHS-fed rats displayed diet-induced changes in prefrontal cortex (PFC) function which were detected by altered expression of GABAergic parvalbumin-expressing inhibitory interneurons and the stable transcription factor ΔFosB which accumulates in the PFC in response to chronic stimuli. Immunohistochemical analyses of the medial PFC revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells and increased levels of FosB/ΔFosB expression in the infralimbic cortex, a region implicated in the consolidation of fear extinction. There was a trend towards increased IBA-1 immunoreactivity, a marker of microglial activation, in the infralimbic cortex after HFHS diet exposure but expression of the extracellular glycoprotein reelin was unaffected. These findings demonstrate that a HFHS diet during adolescence is associated with reductions of prefrontal parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability in obese individuals to the development of anxiety disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Low-affinity FcγR interactions can decide the fate of novel human IgG-sensitised red blood cells and platelets

    PubMed Central

    Armour, Kathryn L; Smith, Cheryl S; Turner, Craig P; Kirton, Christopher M; Wilkes, Anthony M; Hadley, Andrew G; Ghevaert, Cedric; Williamson, Lorna M; Clark, Michael R

    2014-01-01

    G1Δnab is a mutant human IgG1 constant region with a lower ability to interact with FcγR than the natural IgG constant regions. Radiolabelled RBCs and platelets sensitised with specific G1Δnab Abs were cleared more slowly from human circulation than IgG1-sensitised counterparts. However, non-destructive splenic retention of G1Δnab-coated RBCs required investigation and plasma radioactivities now suggest this also occurred for platelets sensitised with an IgG1/G1Δnab mixture. In vitro assays with human cells showed that G1Δnab-sensitised RBCs did not cause FcγRI-mediated monocyte activation, FcγRIIIa-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) or macrophage phagocytosis although they did adhere to macrophages. Thus, FcγRII was implicated in the adhesion despite the Δnab mutation reducing the already low-affinity binding to this receptor class. Additional contacts via P-selectin enhance the interaction of sensitised platelets with monocytes and this system provided evidence of FcγRII-dependent activation by G1Δnab. These results emphasise the physiological relevance of low-affinity interactions: It appears that FcγRII interactions of G1Δnab allowed splenic retention of G1Δnab-coated RBCs with inhibitory FcγRIIb binding preventing RBC destruction and that FcγRIIb engagement by G1Δnab on IgG1/G1Δnab-sensitised platelets overcame activation by IgG1. Considering therapeutic blocking Abs, G1Δnab offers lower FcγR binding and a greater bias towards inhibition than IgG2 and IgG4 constant regions. PMID:24285214

  15. Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

    PubMed Central

    de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Sechini Cordeiro, Marlon Norberto; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

    2015-01-01

    Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g−1) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment. PMID:26366075

  16. NF-κB Transcriptional Activity Is Modulated by FK506-binding Proteins FKBP51 and FKBP52

    PubMed Central

    Erlejman, Alejandra G.; De Leo, Sonia A.; Mazaira, Gisela I.; Molinari, Alejandro M.; Camisay, María Fernanda; Fontana, Vanina; Cox, Marc B.; Piwien-Pilipuk, Graciela; Galigniana, Mario D.

    2014-01-01

    Hsp90 binding immunophilins FKBP51 and FKBP52 modulate steroid receptor trafficking and hormone-dependent biological responses. With the purpose to expand this model to other nuclear factors that are also subject to nuclear-cytoplasmic shuttling, we analyzed whether these immunophilins modulate NF-κB signaling. It is demonstrated that FKBP51 impairs both the nuclear translocation rate of NF-κB and its transcriptional activity. The inhibitory action of FKBP51 requires neither the peptidylprolyl-isomerase activity of the immunophilin nor its association with Hsp90. The TPR domain of FKBP51 is essential. On the other hand, FKBP52 favors the nuclear retention time of RelA, its association to a DNA consensus binding sequence, and NF-κB transcriptional activity, the latter effect being strongly dependent on the peptidylprolyl-isomerase activity and also on the TPR domain of FKBP52, but its interaction with Hsp90 is not required. In unstimulated cells, FKBP51 forms endogenous complexes with cytoplasmic RelA. Upon cell stimulation with phorbol ester, the NF-κB soluble complex exchanges FKBP51 for FKBP52, and the NF-κB biological effect is triggered. Importantly, FKBP52 is functionally recruited to the promoter region of NF-κB target genes, whereas FKBP51 is released. Competition assays demonstrated that both immunophilins antagonize one another, and binding assays with purified proteins suggest that the association of RelA and immunophilins could be direct. These observations suggest that the biological action of NF-κB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio by favoring NF-κB nuclear retention, recruitment to the promoter regions of target genes, and transcriptional activity. PMID:25104352

  17. Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design.

    PubMed

    de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Cordeiro, Marlon Norberto Sechini; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

    2015-01-01

    Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.

  18. Development of Multifunctional Active Film and Its Application in Modified Atmosphere Packaging of Shiitake Mushrooms.

    PubMed

    Wang, Hong Jiang; An, Duck Soon; Lee, Dong Sun

    2016-09-01

    Agar-based films with multiple functions (CO 2 absorption, water vapor absorption, and antimicrobial activity) were developed, tested for their properties, and then applied to the packaging of fresh shiitake mushrooms as an insert label. The films were cast from an agar-based aqueous solution containing a dissolving plasticizer (glycerol), a CO 2 absorbent (sodium carbonate [SC] alone or a combination of SC and sodium glycinate [SC-SG]), and a volatile antimicrobial agent (carvacrol [CRV]). The agar of the film matrix is designed to serve as a water vapor absorbent. The multifunctional films tended to have poor mechanical properties, with a hard texture and an opaque and yellowish color. The CO 2 absorbent, either SC alone or SC-SG, affected CRV retention and release along with the CO 2 and water vapor absorption behavior. Both films (SC-CRV and SC-SG-CRV films) showed good inhibitory effects against Pseudomonas fluorescens and Saccharomyces cerevisiae . SC-CRV film had a higher and faster CO 2 absorption property, higher retention and extended release of CRV, and lower and slower water vapor absorption and was assessed to be better suited for use in shiitake mushroom packaging. The packaging in which the SC-CRV film with an appropriate amount of CRV was used as an insert label was able to generate the desired atmosphere and less moisture condensation inside the package, producing the best preservation of quality in terms of mushroom color, firmness, flavor score, and microbial counts after 6 days of storage at 10°C. A tailored modified atmosphere packaging system using multifunctional film would be useful in the preservation of CO 2 -sensitive fresh commodities.

  19. Overexpression of protein kinase C ɛ improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction.

    PubMed

    He, H; Zhao, Z-H; Han, F-S; Liu, X-H; Wang, R; Zeng, Y-J

    2016-01-21

    We assessed the effects of protein kinase C ɛ (PKCɛ) for improving stem cell therapy for acute myocardial infarction (AMI). Primary mesenchymal stem cells (MSCs) were harvested from rat bone marrow. PKCɛ-overexpressed MSCs and control MSCs were transplanted into infarct border zones in a rat AMI model. MSCs and PKCɛ distribution and expression of principal proteins involved in PKCɛ signaling through the stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4) axis and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by immunofluorescence and western blot 1 day after transplantation. Echocardiographic measurements and histologic studies were performed at 4 weeks after transplantation, and MSC survival, expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGFβ), cardiac troponin I (cTnI), von Willebrand factor (vWF), smooth muscle actin (SMA) and factor VIII and apoptosis in infarct border zones were assessed. Rat heart muscles retained more MSCs and SDF-1, CXCR4, PI3K and phosphorylated AKT increased with PKCɛ overexpression 1 day after transplantation. MSC survival and VEGF, bFGF, TGFβ, cTnI, vWF, SMA and factor VIII expression increased in animals with PKCɛ-overexpressed MSCs at 4 weeks after transplantation and cardiac dysfunction and remodeling improved. Infarct size and apoptosis decreased as well. Inhibitory actions of CXCR4 or PI3K partly attenuated the effects of PKCɛ. Activation of PKCɛ may improve retention, survival and differentiation of transplanted MSCs in myocardia. Augmentation of PKCɛ expression may enhance the therapeutic effects of stem cell therapy for AMI.

  20. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    PubMed Central

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is concluded that the inhibitory response to nerve stimulation and extract in the BRP may involve several ionic species. However, unlike that in gastrointestinal muscles the NANC response in the BRP is accompanied by an increased membrane resistance and does not primarily involve K+. The underlying mechanisms for the inhibitory response to both NANC nerve stimulation and inhibitory extract appear to be similar, compatible with the view that the latter may contain the inhibitory transmitter released from these nerves in this tissue. PMID:4027462

  1. Conflict Inhibitory Control Facilitates Pretense Quality in Young Preschoolers

    PubMed Central

    Van Reet, Jennifer

    2013-01-01

    The present research explores the role of inhibitory control in young preschoolers’ pretense ability using an ego depletion paradigm. In Experiment 1 (N = 56), children’s pretense ability was assessed either before or after participating in conflict inhibitory control or control tasks, and in Experiment 2 (N = 36), pretense ability was measured after children engaged in either conflict or delay inhibitory control tasks. In both experiments, pretense scores were significantly higher only after engaging in conflict inhibitory control tasks. Further, pretense scores were positively correlated with inhibitory control scores when conflict inhibitory control was not experienced first. This pattern of results suggests that inhibitory control may underlie pretense, and conflict inhibitory control can boost the quality of children’s subsequent pretending. PMID:26074736

  2. Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

    PubMed

    Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

    2018-03-01

    Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

  3. Biodiesel production using waste frying oil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Charpe, Trupti W.; Rathod, Virendra K., E-mail: vk.rathod@ictmumbai.edu.in

    2011-01-15

    Research highlights: {yields} Waste sunflower frying oil is successfully converted to biodiesel using lipase as catalyst. {yields} Various process parameters that affects the conversion of transesterification reaction such as temperature, enzyme concentration, methanol: oil ratio and solvent are optimized. {yields} Inhibitory effect of methanol on lipase is reduced by adding methanol in three stages. {yields} Polar solvents like n-hexane and n-heptane increases the conversion of tranesterification reaction. - Abstract: Waste sunflower frying oil is used in biodiesel production by transesterification using an enzyme as a catalyst in a batch reactor. Various microbial lipases have been used in transesterification reaction tomore » select an optimum lipase. The effects of various parameters such as temperature, methanol:oil ratio, enzyme concentration and solvent on the conversion of methyl ester have been studied. The Pseudomonas fluorescens enzyme yielded the highest conversion. Using the P. fluorescens enzyme, the optimum conditions included a temperature of 45 deg. C, an enzyme concentration of 5% and a methanol:oil molar ratio 3:1. To avoid an inhibitory effect, the addition of methanol was performed in three stages. The conversion obtained after 24 h of reaction increased from 55.8% to 63.84% because of the stage-wise addition of methanol. The addition of a non-polar solvent result in a higher conversion compared to polar solvents. Transesterification of waste sunflower frying oil under the optimum conditions and single-stage methanol addition was compared to the refined sunflower oil.« less

  4. Don't touch the gadget because it's hot! Mothers' and children's behavior in the presence of a contrived hazard at home: implications for supervising children.

    PubMed

    Morrongiello, Barbara A; McArthur, Brae Anne; Goodman, Samantha; Bell, Melissa

    2015-01-01

    This study compared boys' with girls' hazard-directed behaviors at home when the mother was present and absent from the room. Videos were coded for how children reacted to a contrived burn hazard ('Gadget'), maternal verbalizations to children about the hazard, and children's compliance with directives to avoid the hazard. Children's behavioral attributes (risk-taking tendency, inhibitory control) and maternal permissive parenting style were also measured. Boys engaged in more hazard-directed behaviors when the mother was present than absent, whereas girls' risk behaviors did not vary with caregiver presence and was comparable with how boys behaved when the parent was absent. Mothers emphasized reactive communications, and boys received significantly more of these than girls. Permissiveness was associated with fewer statements explaining about safety. Children high in inhibitory control showed fewer hazard-directed behaviors and greater compliance with parent communications, whereas those high in risk-taking propensity showed more hazard-directed behaviors and less compliance. The hazard-directed behaviors of boys and girls vary with caregiver context, with boys reacting to parent presence with increased risk taking. Depending on child attributes, different supervision patterns are needed to keep young children safe in the presence of home hazards. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Evaluation of sensorial, phytochemical and biological properties of new isotonic beverages enriched with lemon and berries during shelf life.

    PubMed

    Gironés-Vilaplana, Amadeo; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

    2014-04-01

    The aim of this work was to design new isotonic drinks with lemon juice and berries: maqui (Aristotelia chilensis (Molina) Stuntz), açaí (Euterpe oleracea Mart.) and blackthorn (Prunus spinosa L.), following previous research. Quality parameters, sensorial attributes, antioxidant activities (ABTS(+), DPPH(•) and O2(•-) assays) and biological capacities (α-glucosidase and lipase inhibitory assays) were evaluated over 70 days of shelf-life period. Maqui isotonic blends were the most active in all antioxidant assays (8.35 and 3.07 mmol L(-1) Trolox for ABTS(+) and DPPH(•)), in the lipase inhibitory assay (43.19 U L(-1)), and showed the highest total phenol content by the Folin-Ciocalteu test (80.97 mg 100 mL(-1) gallic acid), as a result of its higher content of total anthocyanins (42.42 mg 100 mL(-1)). Berry mixtures were also the most potent inhibitors of α-glucosidase between all samples, and displayed an attractive red colour and good sensorial attributes. All the studied parameters remained quite stable during preservation, in general, and the new isotonic drinks can be useful to equilibrate redox balance in acute and intense exercise, and support weight loss programmes, avoiding triglyceride absorption and hyperglycaemia involved in obesity and diabetes mellitus, respectively. Further research in vivo is necessary to verify their beneficial effects for sports, nutrition and health. © 2013 Society of Chemical Industry.

  6. False responses of Renilla luciferase reporter control to nuclear receptor TR4.

    PubMed

    Zhang, Dongyun; Atlasi, Sam S; Patel, Krishna K; Zhuang, Zihao; Heaney, Anthony P

    2017-06-01

    Renilla luciferase reporter is a widely used internal control in dual luciferase reporter assay system, where its transcription is driven by a constitutively active promoter. However, the authenticity of the Renilla luciferase response in some experimental settings has recently been questioned. Testicular receptor 4 (TR4, also known as NR2C2) belongs to the subfamily 2 of nuclear receptors. TR4 binds to a direct repeat regulatory element in the promoter of a variety of target genes and plays a key role in tumorigenesis, lipoprotein regulation, and central nervous system development. In our experimental system using murine pituitary corticotroph tumor AtT20 cells to investigate TR4 actions on POMC transcription, we found that overexpression of TR4 resulted in reduced Renilla luciferase expression whereas knockdown TR4 increased Renilla luciferase expression. The TR4 inhibitory effect was mediated by the TR4 DNA-binding domain and behaved similarly to the GR and its agonist, Dexamethasone. We further demonstrated that the chimeric intron, commonly present in various Renilla plasmid backbones such as pRL-Null, pRL-SV40, and pRL-TK, was responsible for TR4's inhibitory effect. The results suggest that an intron-free Renilla luciferase reporter may provide a satisfactory internal control for TR4 at certain dose range. Our findings advocate caution on the use of Renilla luciferase as an internal control in TR4-directed studies to avoid misleading data interpretation.

  7. Neurocircuit function in eating disorders.

    PubMed

    Friederich, Hans-Christoph; Wu, Mudan; Simon, Joe J; Herzog, Wolfgang

    2013-07-01

    Eating disorders are serious psychosomatic disorders with high morbidity and lifetime mortality. Inadequate response to current therapeutic interventions constitutes a challenging clinical problem. A better understanding of the underlying neurobiological mechanisms could improve psychotherapeutic and drug treatment strategies. A review highlighting the current state of brain imaging in eating disorders related to the anxiety and pathological fear learning model of anorexia nervosa (AN) and the impulsivity model of binge eating in bulimia nervosa (BN). Available neuroimaging studies in patients with acute AN primarily suggest a hyper-responsive emotional and fear network to food, but not necessarily to eating disorder-unrelated, salient stimuli. Furthermore, patients with AN show decreased activation in the ventral fronto-striatal circuits during the performance of a cognitive flexibility task. Results in patients with BN primarily suggest a hypo-responsive reward system to food stimuli, especially to taste reward. Additionally, patients with BN exhibit impaired brain activation in the inhibitory control network during the performance of general response-inhibition tasks. Anxiety and pathological fear learning may lead to conditioned neural stimulus-response patterns to food stimuli and increased cognitive rigidity, which could account for the phobic avoidance of food intake in patients with acute AN. However, further neurobiological studies are required to investigate pathological fear learning in patients with AN. Patients with BN may binge eat to compensate for a hypo-responsive reward system. The impaired brain activation in the inhibitory control network may facilitate the loss of control over food intake in patients with BN. Copyright © 2013 Wiley Periodicals, Inc.

  8. Attention to baseline: does orienting visuospatial attention really facilitate target detection?

    PubMed

    Albares, Marion; Criaud, Marion; Wardak, Claire; Nguyen, Song Chi Trung; Ben Hamed, Suliann; Boulinguez, Philippe

    2011-08-01

    Standard protocols testing the orientation of visuospatial attention usually present spatial cues before targets and compare valid-cue trials with invalid-cue trials. The valid/invalid contrast results in a relative behavioral or physiological difference that is generally interpreted as a benefit of attention orientation. However, growing evidence suggests that inhibitory control of response is closely involved in this kind of protocol that requires the subjects to withhold automatic responses to cues, probably biasing behavioral and physiological baselines. Here, we used two experiments to disentangle the inhibitory control of automatic responses from orienting of visuospatial attention in a saccadic reaction time task in humans, a variant of the classical cue-target detection task and a sustained visuospatial attentional task. Surprisingly, when referring to a simple target detection task in which there is no need to refrain from reacting to avoid inappropriate responses, we found no consistent evidence of facilitation of target detection at the attended location. Instead, we observed a cost at the unattended location. Departing from the classical view, our results suggest that reaction time measures of visuospatial attention probably relie on the attenuation of elementary processes involved in visual target detection and saccade initiation away from the attended location rather than on facilitation at the attended location. This highlights the need to use proper control conditions in experimental designs to disambiguate relative from absolute cueing benefits on target detection reaction times, both in psychophysical and neurophysiological studies.

  9. MALDI-FTICR MS Imaging as a Powerful Tool to Identify Paenibacillus Antibiotics Involved in the Inhibition of Plant Pathogens

    NASA Astrophysics Data System (ADS)

    Debois, Delphine; Ongena, Marc; Cawoy, Hélène; De Pauw, Edwin

    2013-08-01

    Nowadays, microorganisms are more and more often used as biocontrol agents for crop protection against diseases. Among them, bacteria of Bacillus and Paenibacillus genders are already used as commercial biocontrol agents. Their mode of action is supposed to be related to their production of antibiotics, such as cyclic lipopeptides, which exhibit great antimicrobial activities. We chose to work with a Paenibacillus polymyxa strain (Pp56) very resistant to various microorganisms. The bacteria were grown simultaneously with Fusarium oxysporum and we applied matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) mass spectrometry to identify the antibiotics compounds present in the fungus growth inhibition area. We, therefore, identified fusaricidins A, B, and C and numerous members of the LI-F antibiotics family. MALDI-FTICR mass spectrometry imaging was then used to follow the diffusion of lipopeptides involved in the inhibitory activity over time. We analyzed the molecular content of the inhibitory area at different Pp56 and Fusarium incubation durations and concluded that some lipopeptides such as fusaricidin B and a mixture of LI-F05b/06b/08a were mainly involved in the defense mechanism of Pp56. Our study confirms that MALDI imaging may be a powerful tool to quickly determine which molecular species is involved in an antagonism with another microorganism, avoiding time-consuming steps of extraction, purification, and activity tests, which are still commonly used in microbiology.

  10. Modified method for external attachment of transmitters to birds using two subcutaneous anchors

    USGS Publications Warehouse

    Lewis, T.L.; Flint, Paul L.

    2008-01-01

    Of the transmitter attachment techniques for birds, the subcutaneous anchor provides a secure attachment that yields relatively few secondary effects. However, the use of subcutaneous anchors has been limited by transmitter size and retention time. Using a modified method of attachment that utilized two subcutaneous anchors, we deployed 69 GPS transmitters, plus 13 VHF transmitters that were similar in size and weight to GPS models, on Pacific Black Brant (Branta bernicla nigricans). Prior to our study, only harnesses were used for attaching GPS transmitters on birds, mainly because GPS transmitters are too large for other external attachment techniques and implantation in the body cavity attenuates the GPS signal. Thus, to increase the size capacity of anchor attachment and to avoid the well-documented negative effects of harnesses on behavior and survival, we added a second anchor at the transmitter's posterior end. The double-anchor attachment technique was quickly and easily accomplished in the field, requiring bird handling times of <10 min. Incidental recoveries of tagged Brant indicate a high degree of transmitter retention. Five recaptured birds (4-6 weeks after deployment) and eight killed by hunters (3-6 mo after deployment) retained their GPS transmitters. For studies involving the use of relatively large transmitters, the double-anchor method appears to provide a viable alternative for external attachment. ?? 2008 Association of Field Ornithologists.

  11. Treatment and retention of relapsed anterior open-bite with low tongue posture and tongue-tie: A 10-year follow-up

    PubMed Central

    Seo, Yu-Jin; Kim, Su-Jung; Munkhshur, Janchivdorj; Chung, Kyu-Rhim; Ngan, Peter

    2014-01-01

    The purpose of the current report is to present 6-year long-term stability and 10-year follow-up data for an adult patient who was treated with a tongue elevator for relapsed anterior open-bite. The 19-year-old male patient presented with the chief complaint of difficulty in chewing his food. Collectively, clinical and radiographic examinations revealed an anterior open-bite, low tongue posture, and tongue-tie. The patient opted for orthodontic treatment alone, without any surgical procedure. A lingual frenectomy was recommended to avoid the risk of relapse, but the patient declined because he was not experiencing tongue discomfort. Initial treatment of the anterior open-bite with molar intrusion and tongue exercises was successful, but relapse occurred during the retention period. A tongue elevator was used for retreatment, because the approach was minimally invasive and suited the patient's requirements regarding discomfort, cost, and time. The appliance changed the tongue posture and generated an altered tongue force, which ultimately resulted in intrusive dentoalveolar effects, and a subsequent counterclockwise rotation of the mandible. The results showed long-term stability and were maintained for six years through continual use of the tongue elevator. The results of this case indicated that a tongue elevator could be used not only as an alternative treatment for open-bite, but also as an active retainer. PMID:25133135

  12. Evaluating the Capability of Grass Swale for the Rainfall Runoff Reduction from an Urban Parking Lot, Seoul, Korea

    PubMed Central

    Shafique, Muhammad; Kim, Reeho; Kyung-Ho, Kwon

    2018-01-01

    This field study elaborates the role of grass swale in the management of stormwater in an urban parking lot. Grass swale was constructed by using different vegetations and local soil media in the parking lot of Mapu-gu Seoul, Korea. In this study, rainfall runoff was first retained in soil and the vegetation layers of the grass swale, and then infiltrated rainwater was collected with the help of underground perforated pipe, and passed to an underground storage trench. In this way, grass swale detained a large amount of rainwater for a longer period of time and delayed peak discharge. In this field study, various real storm events were monitored and the research results were analyzed to evaluate the performance of grass swale for managing rainfall runoff in an urban area. From the analysis of field experiments, grass swale showed the significant rainfall runoff retention in different rain events. Grass swale markedly reduced total rainfall runoff volume and peak flow during the small storm events of intensity about 30 mm/h. From the analysis, on average rainfall runoff retention from the grass swale was found around 40 to 75% during the various small rain events. From the results, we can say that grass swale is a stormwater mitigation practice which can help avoid flash flooding problems in urban areas. PMID:29547567

  13. AdVance male sling

    PubMed Central

    Chung, Amanda S. J.; Suarez, Oscar A.

    2017-01-01

    The AdVance sling (American Medical Systems, Minnetonka, MN, United States of America) is a synthetic transobturator sling, which is a safe and effective minimally invasive treatment for mild to moderate stress urinary incontinence (SUI) in male patients. This article provides a step-by-step description of our technique for placement of the AdVance male sling, including details and nuances gained from surgical experience, advice for avoidance of complications and discussion on management of complications and sling failures. Patient selection is very important, including exclusion and preoperative treatment of urethral stenosis and bladder dysfunction. Previous pelvic radiation is a poor prognostic factor. In brief, the steps of sling placement are: (I) mobilization of the corpus spongiosum (CS); (II) marking and mobilization of the central tendon; (III) passage of the helical trocar needles exiting at the apex of the angle between the CS and inferior pubic ramus; (IV) fixation of the broad part of the sling body to the CS at the previous mark; (V) cystoscopy during sling tensioning; (VI) placement of a Foley urethral catheter; (VII) Subcutaneous tunnelling of the sling arms back toward the midline; (VIII) wound closure. The most common early postoperative complication is urinary retention but long-term retention is extremely rare. Management of sling failures include placement of an artificial urinary sphincter, repeat AdVance sling, urethral bulking agent or ProACT device. PMID:28904900

  14. Evaluating the Capability of Grass Swale for the Rainfall Runoff Reduction from an Urban Parking Lot, Seoul, Korea.

    PubMed

    Shafique, Muhammad; Kim, Reeho; Kyung-Ho, Kwon

    2018-03-16

    This field study elaborates the role of grass swale in the management of stormwater in an urban parking lot. Grass swale was constructed by using different vegetations and local soil media in the parking lot of Mapu-gu Seoul, Korea. In this study, rainfall runoff was first retained in soil and the vegetation layers of the grass swale, and then infiltrated rainwater was collected with the help of underground perforated pipe, and passed to an underground storage trench. In this way, grass swale detained a large amount of rainwater for a longer period of time and delayed peak discharge. In this field study, various real storm events were monitored and the research results were analyzed to evaluate the performance of grass swale for managing rainfall runoff in an urban area. From the analysis of field experiments, grass swale showed the significant rainfall runoff retention in different rain events. Grass swale markedly reduced total rainfall runoff volume and peak flow during the small storm events of intensity about 30 mm/h. From the analysis, on average rainfall runoff retention from the grass swale was found around 40 to 75% during the various small rain events. From the results, we can say that grass swale is a stormwater mitigation practice which can help avoid flash flooding problems in urban areas.

  15. Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rinaldo, J.E.; English, D.; Levine, J.

    1988-02-01

    Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria.more » However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.« less

  16. Atomic to Nanoscale Investigation of Functionalities of Al2O3 Coating Layer on Cathode for Enhanced Battery Performance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yan, Pengfei; Zheng, Jianming; Zhang, Xiaofeng

    2016-01-06

    Surface coating of cathode has been identified as an effective approach for enhancing the capacity retention of layered structure cathode. However, the underlying operating mechanism of such a thin layer of coating, in terms of surface chemical functionality and capacity retention, remains unclear. In this work, we use aberration corrected scanning transmission electron microscopy and high efficient spectroscopy to probe the delicate functioning mechanism of Al2O3 coating layer on Li1.2Ni0.2Mn0.6O2 cathode. We discovered that in terms of surface chemical function, the Al2O3 coating suppresses the side reaction between cathode and the electrolyte upon the battery cycling. At the same time,more » the Al2O3 coating layer also eliminates the chemical reduction of Mn from the cathode particle surface, therefore avoiding the dissolution of the reduced Mn into the electrolyte. In terms of structural stability, we found that the Al2O3 coating layer can mitigate the layer to spinel phase transformation, which otherwise will initiate from the particle surface and propagate towards the interior of the particle with the progression of the battery cycling. The atomic to nanoscale effects of the coating layer observed here provide insight for optimized design of coating layer on cathode to enhance the battery properties.« less

  17. Production of salted and pressed anchovies (stolephorus sp.) and it's quality evaluation during storage.

    PubMed

    Siriskar, Dipty A; Khedkar, Gulab Dattarao; Lior, David

    2013-12-01

    Present study deals with the production of low cost salted and dried product from anchovy fish (Stolephorus spp.) using traditional technology application of different inhibitory factors to achieve a reasonable shelf life at ambient tropical temperature. Microbial safety, nutrient retention and product quality in terms of flavor and texture after rehydration have been tested. This product has been subjected to storage studies, with respect to product quality and microbial status. It can be kept well for a period of 5 weeks. The quality changes during storage are; decrease in sensory scores for the overall acceptance and also for the individual attributes. Increase in nitrogenous components such as Total Volatile Bases Nitrogen (TVB-N), Tri Methyl Amine Nitrogen (TMA-N) and Alpha Amino Nitrogen (AAN) was obtained with the advancement of the storage period. The lipid quality of the fish showed gradual increase in Preoxide Value (PV) and Free Fatty Acid (FFA) accompanied by decrease in flavor and odor scores. Activity of microorganisms showed a marginal increase with increase in storage period.

  18. Iodinated curcumin bearing dermal cream augmented drug delivery, antimicrobial and antioxidant activities.

    PubMed

    Manchanda, Gagandeep; Sodhi, Rupinder Kaur; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

    2018-01-01

    Curcumin (Cur) exhibits weak microbicidal activity owing to high lipophilicity and low cell permeability. Therefore, in the present investigation, Cur was iodinated using elemental iodine (I 2 ) to synthesise Cur-I 2 powder that was later formulated as Cur-I 2 dermal cream and characterised in vitro for antimicrobial and antioxidant activities. Electrophilic addition of I 2 saturated the olefinic bonds of Cur, as confirmed by UV/visible spectroscopy, FT-IR, 1 H NMR and DSC techniques. In addition, in vitro skin permeation and retention analysis indicated that Cur-I 2 cream followed the first order and Higuchi model for drug release through the rat skin. The minimum inhibitory concentration (MIC) of Cur-I 2 powder was measured to be 60 and 90 µg/ml significantly (p < 0.05) lower than 150 and 120 µg/ml of Cur against Staphylococcus aureus and Escherichia coli, respectively. Moreover, Cur-I 2 also exhibited strong antioxidant potential. Cur-I 2 cream warrants further in vivo study to scale up the technology for clinical translation.

  19. The characterization of edible coating from tilapia surimi as a biodegradable packaging

    NASA Astrophysics Data System (ADS)

    Saputra, E.; Alamsjah, A.; Abdillah, A. A.

    2018-04-01

    One of the problems that often arise in the fisheries sector is maintaining the quality. In the room temperature, the fish more quickly enter the phase of rigor mortis and lasted shorter. The retention of fresh fish can be extended by adding antibacterial compounds in the form of synthetic chemicals or natural ingredients. One of the safe natural ingredients used to extend the freshness of the fish is the edible coating. Edible coatings may be composed of hydrocolloid, lipids and composites. In the food industry surimi can be used as an ingredient to make edible packaging or better known in the form of edible film and protein-based edible coating. Edible film and potential coatings are used as packaging materials as they may affect food quality, food safety, and shelf life. Protein-based edible film have superior inhibitory and mechanical properties compared to polysaccharide-based ones. This is because protein contains 20 different amino acids and has most special characteristics that produce functional characteristics when compared with polysaccharides used as an ingredient in edible film and coating making most homopolymers.

  20. The Steroid Hormone 20-Hydroxyecdysone Up-regulates Ste-20 Family Serine/Threonine Kinase Hippo to Induce Programmed Cell Death*

    PubMed Central

    Dong, Du-Juan; Jing, Yu-Pu; Liu, Wen; Wang, Jin-Xing; Zhao, Xiao-Fan

    2015-01-01

    The steroid hormone 20-hydroxyecdysone (20E) and the serine/threonine Ste20-like kinase Hippo signal promote programmed cell death (PCD) during development, although the interaction between them remains unclear. Here, we present evidence that 20E up-regulates Hippo to induce PCD during the metamorphic development of insects. We found that Hippo is involved in 20E-induced metamorphosis via promoting the phosphorylation and cytoplasmic retention of Yorkie (Yki), causing suppressed expression of the inhibitor of apoptosis (IAP), thereby releasing its inhibitory effect on caspase. Furthermore, we show that 20E induced the expression of Hippo at the transcriptional level through the ecdysone receptor (EcR), ultraspiracle protein (USP), and hormone receptor 3 (HR3). We also found that Hippo suppresses the binding of Yki complex to the HR3 promoter. In summary, 20E up-regulates the transcription of Hippo via EcRB1, USP1, and HR3 to induce PCD, and Hippo has negative feedback effects on HR3 expression. These two signaling pathways coordinate PCD during insect metamorphosis. PMID:26272745

  1. Reverse membrane bioreactor: Introduction to a new technology for biofuel production.

    PubMed

    Mahboubi, Amir; Ylitervo, Päivi; Doyen, Wim; De Wever, Heleen; Taherzadeh, Mohammad J

    2016-01-01

    The novel concept of reverse membrane bioreactors (rMBR) introduced in this review is a new membrane-assisted cell retention technique benefiting from the advantageous properties of both conventional MBRs and cell encapsulation techniques to tackle issues in bioconversion and fermentation of complex feeds. The rMBR applies high local cell density and membrane separation of cell/feed to the conventional immersed membrane bioreactor (iMBR) set up. Moreover, this new membrane configuration functions on basis of concentration-driven diffusion rather than pressure-driven convection previously used in conventional MBRs. These new features bring along the exceptional ability of rMBRs in aiding complex bioconversion and fermentation feeds containing high concentrations of inhibitory compounds, a variety of sugar sources and high suspended solid content. In the current review, the similarities and differences between the rMBR and conventional MBRs and cell encapsulation regarding advantages, disadvantages, principles and applications for biofuel production are presented and compared. Moreover, the potential of rMBRs in bioconversion of specific complex substrates of interest such as lignocellulosic hydrolysate is thoroughly studied. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. GABAB receptor cell surface export is controlled by an endoplasmic reticulum gatekeeper

    PubMed Central

    Doly, Stéphane; Shirvani, Hamasseh; Gäta, Gabriel; Meye, Frank; Emerit, Michel-Boris; Enslen, Hervé; Achour, Lamia; Pardo-Lopez, Liliana; Kwon, Yang Seung; Armand, Vincent; Gardette, Robert; Giros, Bruno; Gassmann, Martin; Bettler, Bernhard; Mameli, Manuel; Darmon, Michèle; Marullo, Stefano

    2016-01-01

    Summary Endoplasmic reticulum (ER) release and cell surface export of many G protein-coupled receptors (GPCRs), are tightly regulated. For GABAB receptors of GABA, the major mammalian inhibitory neurotransmitter, the ligand-binding GB1 subunit is maintained in the ER by unknown mechanisms in the absence of hetero-dimerization with the GB2 subunit. We report that GB1 retention is regulated by a specific gatekeeper, PRAF2. This ER resident transmembrane protein binds to GB1, preventing its progression in the biosynthetic pathway. GB1 release occurs upon competitive displacement from PRAF2 by GB2. PRAF2 concentration, relative to that of GB1 and GB2, tightly controls cell surface receptor density and controls GABAB function in neurons. Experimental perturbation of PRAF2 levels in vivo caused marked hyperactivity disorders in mice. These data reveal an unanticipated major impact of specific ER gate-keepers on GPCR function and identify PRAF2 as a new molecular target with therapeutic potential for psychiatric and neurological diseases involving GABAB function. PMID:26033241

  3. Biomass adaptation over anaerobic co-digestion of sewage sludge and trapped grease waste.

    PubMed

    Silvestre, G; Rodríguez-Abalde, A; Fernández, B; Flotats, X; Bonmatí, A

    2011-07-01

    The feasibility of sewage sludge co-digestion using intermediate waste generated inside a wastewater treatment plant, i.e. trapped grease waste from the dissolved air flotation unit, has been assessed in a continuous stirred lab reactor operating at 35°C with a hydraulic retention time of 20 days. Three different periods of co-digestion were carried out as the grease waste dose was increased. When the grease waste addition was 23% of the volatile solids fed (organic loading rate 3.0 kg(COD)m(-3)d(-1)), an increase in methane yield of 138% was reported. Specific activity tests suggested that anaerobic biomass had adapted to the co-substrate. The adapted inoculum showed higher acetoclastic methanogenic and β-oxidation synthrophic acetogenic activities but lower hydrogenotrophic methanogenic activity. The results indicate that a slow increase in the grease waste dose could be a strategy that favours biomass acclimation to fat-rich co-substrate, increases long chain fatty acid degradation and reduces the latter's inhibitory effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

    PubMed

    Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

    2017-09-06

    Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant therapeutic agent for memory deficits in patients with PD receiving L-DOPA.

  5. Ocular Injury With Chestnut Burr: Our Experience.

    PubMed

    García-García, Gerardo P; Esaa-Caride, Neyla C; Jurado-Guano, Nancy D; Muñoz-Bellido, Luis

    2016-10-01

    To evaluate the medical and surgical management and treatment of ocular injuries with chestnut burr recorded at the Hospital El Bierzo between 2009 and 2015. A prospective study of ocular injuries with chestnut burr was conducted for the period from 2009 to 2015. Patients were detected in the Emergency Department and referred to the Ophthalmology Department for study and medical and surgical treatment. Ten eyes were evaluated in 10 patients. The injuries ranged from ocular contusion without corneal involvement to trauma with corneal perforation caused by spines. One patient with chronic retention of spines in the intrastromal corneal ring was included. Six of the eyes studied had chestnut burr spines in the cornea, one of which was chronically retained in the intrastromal cornea. One case of spine-induced corneal perforation was also studied. Six of the patients required surgery, 2 required removal of the spine using a slit lamp, 2 required outpatient medical treatments, and a wait-and-see approach was taken in 1 patient. All patients progressed favorably, and no surgical complications were recorded. Proper occupational risk prevention and the use of eye protection glasses are fundamental in avoiding these accidents. Once they have occurred, medical and surgical management must be done early and on an individual basis depending on the severity and location of the injuries, to avoid potentially serious complications.

  6. Spinal instrumentation for Duchenne's muscular dystrophy: experience of hypotensive anaesthesia to minimise blood loss.

    PubMed

    Fox, H J; Thomas, C H; Thompson, A G

    1997-01-01

    Nineteen patients with Duchenne's muscular dystrophy underwent segmental spinal instrumentation and posterior fusion between 1989 and 1994. The indication for surgery was loss of the ability to walk and development of scoliosis with sitting discomfort. Preoperative assessment included evaluation of pulmonary function. Average age at operation was 12.5 years. Instrumentation and fusion extended from upper thoracic levels to L-5 or the sacrum. A Hartshill rectangle was used in all cases, with banked allograft bone. Severe intraoperative blood loss was avoided by use of hypotensive anaesthesia. Peroperatively, systolic blood pressure was maintained between 75 and 85 mm Hg. Average blood loss was 1,246 ml (range, 400-3,100) or 30% of estimated total blood volume. Average transfusion requirements were 3 units of packed cells. Postoperative analgesia was provided by infusion via an epidural catheter. There were no postoperative wound or chest infections. Three patients required catheterisation for urinary retention. Postoperatively patients were fitted with a Neofract jacket to allow early mobilisation and discharge. Mean postoperative length of stay was 16 days. Posterior spinal fusion by using the Hartshill rectangle provided good correction and fixation. Hypotensive anaesthesia permitted surgery to be performed rapidly in a relatively dry field and avoided the complications of severe intraoperative blood loss and massive transfusion.

  7. Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat.

    PubMed

    Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Kazeminejad, Behrang

    2010-10-01

    Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. In this study, the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity was investigated. Curcumin (5 and 50mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intrahippocampal injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24h after the last Curcumin or its vehicle injection. We detected Malondialdehyde (MDA) and Super oxide anion (SOA) in rats' hippocampi. Results indicated that Hcy could induce lipid peroxidation and increase MDA and SOA levels in rats' hippocampi. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rats' hippocampi and polyphenol treatment (Curcumin) improved learning and memory deficits by protecting the nervous system against Hcy toxicity. (c) 2010 Elsevier Inc. All rights reserved.

  8. Flavones from Erythrina falcata are modulators of fear memory.

    PubMed

    de Oliveira, Daniela Rodrigues; Zamberlam, Cláudia R; Gaiardo, Renan Barreta; Rêgo, Gizelda Maia; Cerutti, Janete M; Cavalheiro, Alberto J; Cerutti, Suzete M

    2014-08-05

    Flavonoids, which have been identified in a variety of plants, have been demonstrated to elicit beneficial effects on memory. Some studies have reported that flavonoids derived from Erythrina plants can provide such beneficial effects on memory. The aim of this study was to identify the flavonoids present in the stem bark crude extract of Erythrina falcata (CE) and to perform a bioactivity-guided study on conditioned fear memory. The secondary metabolites of CE were identified by high performance liquid chromatography combined with a diode array detector, electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MSn) and nuclear magnetic resonance (NMR). The buthanolic fraction (BuF) was obtained by partitioning. Subfractions from BuF (BuF1 - BuF6) and fraction flavonoidic (FfA and FfB) were obtained by flash chromatography. The BuF3 and BuF4 fractions were used for the isolation of flavonoids, which was performed using HPLC-PAD. The isolated substances were quantified by HPLC-DAD and their structures were confirmed by nuclear magnetic resonance (NMR). The activities of CE and the subfractions were monitored using a one-trial, step-down inhibitory avoidance (IA) task to identify the effects of these substances on the acquisition and extinction of conditioned fear in rats. Six subclasses of flavonoids were identified for the first time in CE. According to our behavioral data, CE, BuF, BuF3 and BuF4, the flavonoidic fractions, vitexin, isovitexin and 6-C-glycoside-diosmetin improved the acquisition of fear memory. Rats treated with BuF, BuF3 and BuF4 were particularly resistant to extinction. Nevertheless, rats treated with FfA and FfB, vitexin, isovitexin and 6-C-glycoside-diosmetin exhibited gradual reduction in conditioned fear response during the extinction retest session, which was measured at 48 to 480 h after conditioning. Our results demonstrate that vitexin, isovitexin and diosmetin-6-C-glucoside and flavonoidic fractions resulted in a significant retention of fear memory but did not prevent the extinction of fear memory. These results further substantiate that the treatment with pure flavonoids or flavanoid-rich fractions might represent potential therapeutic approaches for the treatment of neurocognitive disorders, improvement of memory acquisition and spontaneous recovery of fear.

  9. Cross state-dependency of learning between arachidonylcyclopropylamide (ACPA) and muscimol in the mouse dorsal hippocampus.

    PubMed

    Jafari-Sabet, Majid; Karimi, Amir-Mohammad

    2017-12-01

    The aim of the present study was to examine cross state-dependent learning between ACPA (a selective cannabinoid CB1 receptor agonist) and muscimol (a selective GABAA receptor agonist) in the step-down inhibitory avoidance learning task. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection. Post-training and/or pre-test administration of ACPA (1 and 2ng/mouse) dose-dependently induced amnesia. Pre-test microinjection of the same doses of ACPA reversed the post-training ACPA-induced amnesia. This event has been named ACPA state-dependent learning (SDL). Post-training and/or pre-test microinjection of muscimol (0.05 and 0.1μg/mouse) dose-dependently induced amnesia. Pre-test administration of the same doses of muscimol reversed the post-training muscimol-induced amnesia, suggesting muscimol SDL. The amnesia induced by post-training administration of ACPA was reversed by pre-test administration of muscimol (0.05 and 0.1μg/mouse). Furthermore, the pre-test microinjection of muscimol (0.025 and 0.05μg/mouse) with an ineffective dose of ACPA (0.5ng/mouse) significantly restored memory retrieval and induced ACPA SDL. In another series of experiments, the amnesia induced by post-training administration of muscimol was reversed by pre-test administration of ACPA (1 and 2ng/mouse). Moreover, pre-test microinjection of ACPA (0.5 and 1ng/mouse) with an ineffective dose of muscimol (0.025μg/mouse) significantly restored memory retrieval and induced muscimol SDL. It is important to note that pre-test intra-CA1 injection of a selective GABAA receptor antagonist, bicuculline (0.125 and 0.25μg/mouse), 5min before the administration of muscimol (0.1μg/mouse) or ACPA (2ng/mouse) dose-dependently inhibited muscimol- and ACPA-induced SDL, respectively. Pre-test intra-CA1 administration of bicuculline (0.0625, 0.125 and 0.25μg/mouse) by itself did not affect memory retention. In conclusion, the data strongly revealed a cross SDL among ACPA and muscimol in the dorsal hippocampal CA1 regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

    PubMed

    Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

    2016-04-13

    The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal models in which compensatory mechanisms may occur. To avoid these issues, some studies have been done using viral overexpression of PKMζ in different brain structures to show cognitive enhancement. However, electrophysiological experiments were exclusively done in knock-out models or inhibitory studies to show depletion of LTP. There was no study showing the effect of PKMζ overexpression in the hippocampus on behavior and LTP experiments. To our knowledge, this is the first study to combine these aspects with the result of enhanced memory for contextual fear memory and to show enhanced LTP in hippocampal slices overexpressing PKMζ. Copyright © 2016 Schuette et al.

  11. Do Children with Better Inhibitory Control Donate More? Differentiating between Early and Middle Childhood and Cool and Hot Inhibitory Control.

    PubMed

    Hao, Jian

    2017-01-01

    Inhibitory control may play an important part in prosocial behavior, such as donating behavior. However, it is not clear at what developmental stage inhibitory control becomes associated with donating behavior and which aspects of inhibitory control are related to donating behavior during development in early to middle childhood. The present study aimed to clarify these issues with two experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool (Stroop-like) and hot (delay of gratification) inhibitory control tasks and a donating task. The results indicated that there were no relationships between cool or hot inhibitory control and donating behavior in the whole group and each age group of the preschoolers. In Experiment 2, 140 elementary school children in Grades 2, 4, and 6 completed cool (Stroop-like) and hot (delay of gratification) inhibitory control tasks and a donating task. The results showed that inhibitory control was positively associated with donating behavior in the whole group. Cool and hot inhibitory control respectively predicted donating behavior in the second and sixth graders. Therefore, the present study reveals that donating behavior increasingly relies on specific inhibitory control, i.e., hot inhibitory control as children grow in middle childhood.

  12. Evaluation of an optimal fill strategy to biodegrade inhibitory wastewater using an industrial prototype discontinuous reactor.

    PubMed

    Buitrón, G; Moreno-Andrade, I; Linares-García, J A; Pérez, J; Betancur, M J; Moreno, J A

    2007-01-01

    This work presents the results and discussions of the application of an optimally controlled influent flow rate strategy to biodegrade, in a discontinuous reactor, a synthetic wastewater constituted by 4-chlorophenol. An aerobic automated discontinuous reactor system of 1.3 m3, with a useful volume of 0.75 m3 and an exchange volume of 60% was used. As part of the control strategy influent is fed into the reactor in such a way as to obtain the maximal degradation rate avoiding inhibition of microorganisms. Such an optimal strategy was able to manage increments of 4-chlorophenol concentrations in the influent between 250 and 1000 mg/L. it was shown that the optimally controlled influent flow rate strategy brings savings in reaction time and flexibility in treating high concentrations of an influent with toxic characteristics.

  13. Anaerobic Codigestion of Sludge: Addition of Butcher's Fat Waste as a Cosubstrate for Increasing Biogas Production.

    PubMed

    Martínez, E J; Gil, M V; Fernandez, C; Rosas, J G; Gómez, X

    2016-01-01

    Fat waste discarded from butcheries was used as a cosubstrate in the anaerobic codigestion of sewage sludge (SS). The process was evaluated under mesophilic and thermophilic conditions. The codigestion was successfully attained despite some inhibitory stages initially present that had their origin in the accumulation of volatile fatty acids (VFA) and adsorption of long-chain fatty acids (LCFA). The addition of a fat waste improved digestion stability and increased biogas yields thanks to the higher organic loading rate (OLR) applied to the reactors. However, thermophilic digestion was characterized by an effluent of poor quality and high VFA content. Results from spectroscopic analysis suggested the adsorption of lipid components onto the anaerobic biomass, thus disturbing the complete degradation of substrate during the treatment. The formation of fatty aggregates in the thermophilic reactor prevented process failure by avoiding the exposure of biomass to the toxic effect of high LCFA concentrations.

  14. Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

    NASA Astrophysics Data System (ADS)

    Chen, Shiyu; Gopalakrishnan, Ranganath; Schaer, Tifany; Marger, Fabrice; Hovius, Ruud; Bertrand, Daniel; Pojer, Florence; Heinis, Christian

    2014-11-01

    The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability.

  15. A visually guided collision warning system with a neuromorphic architecture.

    PubMed

    Okuno, Hirotsugu; Yagi, Tetsuya

    2008-12-01

    We have designed a visually guided collision warning system with a neuromorphic architecture, employing an algorithm inspired by the visual nervous system of locusts. The system was implemented with mixed analog-digital integrated circuits consisting of an analog resistive network and field-programmable gate array (FPGA) circuits. The resistive network processes the interaction between the laterally spreading excitatory and inhibitory signals instantaneously, which is essential for real-time computation of collision avoidance with a low power consumption and a compact hardware. The system responded selectively to approaching objects of simulated movie images at close range. The system was, however, confronted with serious noise problems due to the vibratory ego-motion, when it was installed in a mobile miniature car. To overcome this problem, we developed the algorithm, which is also installable in FPGA circuits, in order for the system to respond robustly during the ego-motion.

  16. Anaerobic Codigestion of Sludge: Addition of Butcher’s Fat Waste as a Cosubstrate for Increasing Biogas Production

    PubMed Central

    Martínez, E. J.; Gil, M. V.; Fernandez, C.; Rosas, J. G.

    2016-01-01

    Fat waste discarded from butcheries was used as a cosubstrate in the anaerobic codigestion of sewage sludge (SS). The process was evaluated under mesophilic and thermophilic conditions. The codigestion was successfully attained despite some inhibitory stages initially present that had their origin in the accumulation of volatile fatty acids (VFA) and adsorption of long-chain fatty acids (LCFA). The addition of a fat waste improved digestion stability and increased biogas yields thanks to the higher organic loading rate (OLR) applied to the reactors. However, thermophilic digestion was characterized by an effluent of poor quality and high VFA content. Results from spectroscopic analysis suggested the adsorption of lipid components onto the anaerobic biomass, thus disturbing the complete degradation of substrate during the treatment. The formation of fatty aggregates in the thermophilic reactor prevented process failure by avoiding the exposure of biomass to the toxic effect of high LCFA concentrations. PMID:27071074

  17. Control strategies of 3-cell Central Pattern Generator via global stimuli

    NASA Astrophysics Data System (ADS)

    Lozano, Álvaro; Rodríguez, Marcos; Barrio, Roberto

    2016-03-01

    The study of the synchronization patterns of small neuron networks that control several biological processes has become an interesting growing discipline. Some of these synchronization patterns of individual neurons are related to some undesirable neurological diseases, and they are believed to play a crucial role in the emergence of pathological rhythmic brain activity in different diseases, like Parkinson’s disease. We show how, with a suitable combination of short and weak global inhibitory and excitatory stimuli over the whole network, we can switch between different stable bursting patterns in small neuron networks (in our case a 3-neuron network). We develop a systematic study showing and explaining the effects of applying the pulses at different moments. Moreover, we compare the technique on a completely symmetric network and on a slightly perturbed one (a much more realistic situation). The present approach of using global stimuli may allow to avoid undesirable synchronization patterns with nonaggressive stimuli.

  18. A new bio-inspired stimulator to suppress hyper-synchronized neural firing in a cortical network.

    PubMed

    Amiri, Masoud; Amiri, Mahmood; Nazari, Soheila; Faez, Karim

    2016-12-07

    Hyper-synchronous neural oscillations are the character of several neurological diseases such as epilepsy. On the other hand, glial cells and particularly astrocytes can influence neural synchronization. Therefore, based on the recent researches, a new bio-inspired stimulator is proposed which basically is a dynamical model of the astrocyte biophysical model. The performance of the new stimulator is investigated on a large-scale, cortical network. Both excitatory and inhibitory synapses are also considered in the simulated spiking neural network. The simulation results show that the new stimulator has a good performance and is able to reduce recurrent abnormal excitability which in turn avoids the hyper-synchronous neural firing in the spiking neural network. In this way, the proposed stimulator has a demand controlled characteristic and is a good candidate for deep brain stimulation (DBS) technique to successfully suppress the neural hyper-synchronization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The Role of Inhibitory Control in Behavioral and Physiological Expressions of Toddler Executive Function

    PubMed Central

    Morasch, Katherine C.; Bell, Martha Ann

    2010-01-01

    Eighty-one toddlers (ranging from 24 to 27 months) participated in a biobehavioral investigation of inhibitory control. Maternal-report measures of inhibitory control were related to laboratory tasks assessing inhibitory abilities under conditions of conflict, delay, and compliance challenge as well as toddler verbal ability. Additionally, unique variance in inhibitory control was explained by task-related changes in brain electrical activity at lateral frontal scalp sites as well as concurrent inhibitory task performance. Implications regarding neural correlates of executive function in early development and a central, organizing role of inhibitory processing in toddlerhood are discussed. PMID:20719337

  20. Co-inhibitory immune checkpoints in head and neck squamous cell carcinoma.

    PubMed

    Deng, W-W; Wu, L; Sun, Z-J

    2018-03-01

    The upregulation of co-inhibitory immune checkpoints hampers the immune response toward tumor cells and facilitates the tumor cells ability to evade immunosurveillance. Specific inhibitory immune checkpoint delivers inhibitory signals to T cells using multiple mechanisms. More in-depth understanding of the co-inhibitory immune checkpoints could be exploited for head and neck squamous cell carcinoma (HNSCC) treatment. In this review, we summarize the expression and the mechanism of partial co-inhibitory immune checkpoint signals and discuss targeting co-inhibitory immune checkpoints as an immunotherapeutic target for cancer therapy. This review may provide a better understanding of the co-inhibitory immune checkpoints and could promote applications of immunotherapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

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