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Sample records for conditions significantly induces

  1. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    International Nuclear Information System (INIS)

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A.

    1990-01-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01)

  2. Formal conditions for the significance-effect

    DEFF Research Database (Denmark)

    Thellefsen, Torkild Leo; Sørensen, Bent; Thellefsen, Martin

    2006-01-01

    The significance-effect is the right effect of meaning caused upon an interpreting mind. The right effect is understood as the right interpretation of an intended meaning caused by a sign communicated by an utterer. In the article, which is inspired by Charles S. Peirce's doctrine of signs, his s...... semeiotics and his theory of communication, we account for the formal conditions that have to be present for the release of the significance-effect....

  3. The Protective Effect of Conditioning on Noise-Induced Hearing Loss Is Frequency-Dependent

    Directory of Open Access Journals (Sweden)

    Akram Pourbakht

    2012-10-01

    Full Text Available We compared the extent of temporary threshold shift (TTS and hair cell loss following high level 4 kHz noise exposure with those preconditioned with moderate level 1 and 4 kHz octave band noise. Fifteen Male albino guinea pigs (300- 350 g in weight were randomly allocated into three groups: those exposed to 4 kHz octave band noise at 102 dB SPL (group 1, n=5; those conditioned with 1 kHz octave band noise at 85 dB SPL, 6 hours per day for 5 days, then exposed to noise (group 2, n=5; those conditioned with 4 kHz octave band noise at 85 dB SPL, then exposed to noise (group 3, n=5. An hour and one week after noise exposure, threshold shifts were evaluated by auditory-evoked brainstem response (ABR and then animals were euthanized for histological evaluation. We found that TTS and cochlear damage caused by noise exposure were significantly reduced by 1 kHz and 4 kHz conditioning (P<0.001. We also showed that 4 kHz protocol attenuates noise- induced TTS but no significant TTS reduction occurred by 1 kHz conditioning. Both protocol protected noise-induced cochlear damage. We concluded that lower tone conditioning could not protect against higher tone temporary noise-induced hearing loss, thus conditioning is a local acting and frequency-dependent phenomenon.

  4. State-dependent interaction in the antihistamine-induced disruption of a radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1982-01-01

    Two experiments were run to evaluate the possibility that injection of antihistamine can produce a state-dependent acquisition of a radiation-induced conditioned taste aversion. In the first experiment, pretreating rats with the antihistamine chlorpheniramine maleate prior to their initial exposure to sucrose and to low-level irradiation on the conditioning day did not prevent the acquisition of a taste aversion to sucrose when the antihistamine was also administered prior to a subsequent preference test. In the second experiment, rats were both conditioned and tested for a radiation-induced aversion in a drug-free state. Under these condtions, the rats continued to show an aversion to sucrose despite pretreating them with chlorpheniramine prior to irradiation. Since rats conditioned under the antihistamine do not show the radiation-induced conditioned taste aversion when tested for sucrose preference in a nondrug state, it would seem that pretreating rats with an antihistamine prior to conditioning affects only the retrieval of the previously learned response and not its acquisition

  5. Bee venom suppresses methamphetamine-induced conditioned place preference in mice.

    Science.gov (United States)

    Kwon, Young Bae; Li, Jing; Kook, Ji Ae; Kim, Tae Wan; Jeong, Young Chan; Son, Ji Seon; Lee, Hyejung; Kim, Kee Won; Lee, Jang Hern

    2010-02-01

    Although acupuncture is most commonly used for its analgesic effect, it has also been used to treat various drug addictions including cocaine and morphine in humans. This study was designed to investigate the effect of bee venom injection on methamphetamine-induced addictive behaviors including conditioned place preference and hyperlocomotion in mice. Methamphetamine (1 mg/kg) was subcutaneously treated on days 1, 3 and 5 and the acquisition of addictive behaviors was assessed on day 7. After confirming extinction of addictive behaviors on day 17, addictive behaviors reinstated by priming dose of methamphetamine (0.1 mg/kg) was evaluated on day 18. Bee venom (20 microl of 1 mg/ml in saline) was injected to the acupuncture point ST36 on days 1, 3 and 5. Repeated bee venom injections completely blocked development of methamphetamine-induced acquisition and subsequent reinstatement. Single bee venom acupuncture 30 minutes before acquisition and reinstatement test completely inhibited methamphetamine-induced acquisition and reinstatement. Repeated bee venom acupunctures from day 8 to day 12 after methamphetamine-induced acquisition partially but significantly suppressed reinstatement. These findings suggest that bee venom acupuncture has a preventive and therapeutic effect on methamphetamine-induced addiction.

  6. Comparative study; physiological and biochemical parameters of normal and induced dehydrated condition of rabbits

    International Nuclear Information System (INIS)

    Bashir, S.; Bukhari, I.

    2008-01-01

    Biochemical and physiological parameters like body weight, blood pH. Blood glucose, total lipids total protein, globulin, albumin and albumin/globulin ratio were determined in twelve rabbits each normal and after the induction of diseased condition i.e. dehydration. Statistically significant differences were identified when the comparison made between normal rabbits and their respective dehydrated group. Blood glucose total lipid packed cell. Volume and globulin increased significantly where where as body weight, albumin and albumin/globulin ratio decreased significantly. These differences in the physiological and biochemical parameters in disease induced condition require the necessity for analyzing this condition for the changes in the pharmacokinetics parameter like, absorption distribution metabolism and excretion leading to alteration in the pharmacokinetics of drug. (author)

  7. Can overeating induce conditioned taste avoidance in previously food restricted rats?

    Science.gov (United States)

    Hertel, Amanda; Eikelboom, Roelof

    2010-03-30

    While feeding is rewarding, the feeling of satiation has been theorized to have a mixed affect. Using a food restriction model of overeating we examined whether bingeing was capable of supporting conditioned taste avoidance (CTA). Adult male Sprague-Dawley rats were maintained on either an ad lib (n=8) or restricted (50% of regular consumption; n=24) food access for 20 days. On Days 9, 14, and 19 all rats were given access to a novel saccharin solution in place of water, and two groups of food restricted rats were given access to either 100% of regular food consumption or ad lib food. Ad lib access in the restricted rats induced significant overeating on all three exposures. After all rats were returned to ad lib feeding, a 24h two-bottle saccharin/water choice test displayed significantly reduced saccharin consumption in the overeating rats, compared to those in the other 3 groups. To determine whether this avoidance was due to a learned association, a second experiment used a latent inhibition paradigm, familiarizing half the rats with the saccharin for 8 days prior to pairing it with overeating. Using the design of Experiment 1, with only the continuously ad lib and the restricted to ad lib feeding groups, it was found that the overeating-induced saccharin avoidance was attenuated by the pre-exposure. These results suggest that self-induced overeating is capable of supporting a learned avoidance of a novel solution suggestive of a conditioned satiety or taste avoidance. (c) 2009 Elsevier Inc. All rights reserved.

  8. Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats.

    Science.gov (United States)

    Jerabek, Pavel; Havlickova, Tereza; Puskina, Nina; Charalambous, Chrysostomos; Lapka, Marek; Kacer, Petr; Sustkova-Fiserova, Magdalena

    2017-11-01

    An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10 mg/kg s.c.). On the experimental day, JMV2959 (3 and 6 mg/kg i.p.) or saline were administered before testing. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5 mg/kg s.c.) with or without JMV2959 (3 and 6 mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10-40 mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior.

    Science.gov (United States)

    Ploense, Kyle L; Kerstetter, Kerry A; Wade, Matthew A; Woodward, Nicholas C; Maliniak, Dan; Reyes, Michael; Uchizono, Russell S; Bredy, Timothy W; Kippin, Tod E

    2013-06-01

    Histone deacetylase inhibitors (HDACIs) strengthen memory following fear conditioning and cocaine-induced conditioned place preference. Here, we examined the effects of two nonspecific HDACIs, valproic acid (VPA) and sodium butyrate (NaB), on appetitive learning measured by conditioned stimulus (CS)-induced reinstatement of operant responding. Rats were trained to lever press for food reinforcement and then injected with VPA (50-200 mg/kg, i.p.), NaB (250-1000 mg/kg, i.p.), or saline vehicle (1.0 ml/kg), 2 h before receiving pairings of noncontingent presentation of food pellets preceded by a tone+light cue CS. Rats next underwent extinction of operant responding followed by response-contingent re-exposure to the CS. Rats receiving VPA (100 mg/kg) or NaB (1000 mg/kg) before conditioning displayed significantly higher cue-induced reinstatement than did saline controls. Rats that received either vehicle or VPA (100 mg/kg) before a conditioning session with a randomized relation between presentation of food pellets and the CS failed to show subsequent cue-induced reinstatement with no difference between the two groups. These findings indicate that, under certain contexts, HDACIs strengthen memory formation by specifically increasing the associative strength of the CS, not through an increasing motivation to seek reinforcement. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  10. Significance of Operating Environment in Condition Monitoring of Large Civil Structures

    Directory of Open Access Journals (Sweden)

    Sreenivas Alampalli

    1999-01-01

    Full Text Available Success of remote long-term condition monitoring of large civil structures and developing calibrated analytical models for damage detection, depend significantly on establishing accurate baseline signatures and their sensitivity. Most studies reported in the literature concentrated on the effect of structural damage on modal parameters without emphasis on reliability of modal parameters. Thus, a field bridge structure was studied for the significance of operating conditions in relation to baseline signatures. Results indicate that in practice, civil structures should be monitored for at least one full cycle of in-service environmental changes before establishing baselines for condition monitoring or calibrating finite-element models. Boundary conditions deserve special attention.

  11. Microbiologically induced corrosion of carbon steel under continuous flow conditions

    International Nuclear Information System (INIS)

    Tunaru, Mariana; Dragomir, Maria; Voicu, Anca

    2008-01-01

    Microbiologically induced corrosion is the label generally applied to corrosion involving the action of bacteria on metal surfaces. While different combinations of bacterial species, materials and chemical constituents are interrelated factors, stagnant water is the factor most often mentioned in reported cases. This paper presents the results obtained regarding the testing of microbiologically induced corrosion of carbon steel under continuous flow conditions in the presence of iron-oxidizing bacteria. The tests were performed on coupons of SA106gr.B exposed both in stagnant conditions and in flow conditions. The surfaces of these coupons were studied by metallographic technique, while the developed biofilms were analysed using microbiological technique. The correlation of all the results which were obtained emphasized that the minimizing the occurrence of stagnant or low-flow conditions can prove effective in reducing the risk of microbiologically induced corrosion in plant cooling-water systems. (authors)

  12. The effect of post-conditioning exposure to morphine on the retention of a morphine-induced conditioned taste aversion.

    Science.gov (United States)

    Jacobs, W J; Zellner, D A; LoLordo, V M; Riley, A L

    1981-06-01

    In the following experiment, multiple injections of morphine sulfate following the acquisition of a morphine-induced taste aversion had no effect on the retention of the previously acquired aversion. Post-conditioning injections of morphine resulted in the development of physical dependence to morphine and led to a decrement in the ability of morphine to induce a subsequent aversion to a second novel taste. This failure of post-conditioning exposures to morphine to affect a previously acquired morphine-induced taste aversion even though tolerance to morphine had occurred was discussed in the context of Rescorla's event-memory model of conditioning.

  13. Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

    Science.gov (United States)

    Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

    2014-04-01

    The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

    Science.gov (United States)

    Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

    2010-03-01

    Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior.

  15. Radiation induced bystander effect on hepatoma HepG2 cells under hypoxia condition

    International Nuclear Information System (INIS)

    Zhang Jianghong; Jin Yizun; Shao Chunlin; Prise KM

    2009-01-01

    Objective: To investigate radiation induced bystander effect and its mechanism on hepatoma HepG2 cells under hypoxia condition. Methods: Non-irradiated bystander hepatoma cells were co-cultured with irradiated cells or treated with the conditioned medium (CM) from irradiated cells, then micronuclei (MN) were measured for both irradiated cells and bystander cells. Results: The MN yield of irradiated HepG2 cells under hypoxic condition was significantly lower than that under normoxia, the oxygen enhancement ratio of HepG2 cells of MN was 1.6. For both hypoxic and normoxic condition, the MN yield of bystander cells were obviously enhanced to a similar high level after co-culturing with irradiated cells or with CM treatment, and it also correlated with the irradiation dose. When the hypoxic HepG2 cells were treated with either DMSO, a scavenger of reactive oxygen species (ROS), or aminoguanidine, an iNOS inhibitor, the yield of bystander MN was partly diminished, and the reducing rate of DMSO was 42.2%-46.7%, the reducing rate of aminoguanidine was 42% . Conclusion: ROS, NO and their downstream signal factors are involved in the radiation induced bystander effect of hypoxic HepG2 cells. (authors)

  16. Significance of Operating Environment in Condition Monitoring of Large Civil Structures

    OpenAIRE

    Alampalli, Sreenivas

    1999-01-01

    Success of remote long-term condition monitoring of large civil structures and developing calibrated analytical models for damage detection, depend significantly on establishing accurate baseline signatures and their sensitivity. Most studies reported in the literature concentrated on the effect of structural damage on modal parameters without emphasis on reliability of modal parameters. Thus, a field bridge structure was studied for the significance of operating conditions in relation to bas...

  17. Salmonella Modulates Metabolism During Growth under Conditions that Induce Expression of Virulence Genes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-Mo; Schmidt, Brian; Kidwai, Afshan S.; Jones, Marcus B.; Deatherage, Brooke L.; Brewer, Heather M.; Mitchell, Hugh D.; Palsson, Bernhard O.; McDermott, Jason E.; Heffron, Fred; Smith, Richard D.; Peterson, Scott N.; Ansong, Charles; Hyduke, Daniel R.; Metz, Thomas O.; Adkins, Joshua N.

    2013-04-05

    Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative pathogen that uses complex mechanisms to invade and proliferate within mammalian host cells. To investigate possible contributions of metabolic processes in S. Typhimurium grown under conditions known to induce expression of virulence genes, we used a metabolomics-driven systems biology approach coupled with genome scale modeling. First, we identified distinct metabolite profiles associated with bacteria grown in either rich or virulence-inducing media and report the most comprehensive coverage of the S. Typhimurium metabolome to date. Second, we applied an omics-informed genome scale modeling analysis of the functional consequences of adaptive alterations in S. Typhimurium metabolism during growth under our conditions. Excitingly, we observed possible sequestration of metabolites recently suggested to have immune modulating roles. Modeling efforts highlighted a decreased cellular capability to both produce and utilize intracellular amino acids during stationary phase culture in virulence conditions, despite significant abundance increases for these molecules as observed by our metabolomics measurements. Model-guided analysis suggested that alterations in metabolism prioritized other activities necessary for pathogenesis instead, such as lipopolysaccharide biosynthesis.

  18. Treatment with pioglitazone induced significant, reversible mitral regurgitation.

    Science.gov (United States)

    Dorkhan, Mozhgan; Dencker, Magnus; Frid, Anders

    2008-04-30

    There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

  19. Treatment with pioglitazone induced significant, reversible mitral regurgitation

    Directory of Open Access Journals (Sweden)

    Frid Anders

    2008-04-01

    Full Text Available Abstract There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs. We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

  20. Design retrofit to prevent damage due to heat transport pump operation under conditions of significant void

    Energy Technology Data Exchange (ETDEWEB)

    Lam, K F [Bruce Engineering Department, In-Service Nuclear Projects, Ontario Hydro, North York, ON (Canada)

    1991-04-01

    The purpose of this paper is to provide a general review of certain key design areas which address the safety concerns of HT pump operation under conditions of significant void. To illustrate the challenges confronting designers and analysts, some of the highlights during the design of a protective system to prevent damage to HT piping and pump supports at Bruce NGS 'A' are outlined. The effects of this protective system on reactor safety are also discussed. HI pump operation under conditions of significant void offers a major challenge to designers and analysts to ensure that pump induced vibration and its effects on pump and piping are addressed. For an in-service station the search for a practical solution is often limited by existing. station equipment design and Layout. The diversity of design verification process requires a major commitment of engineering resources to ensure all. safety aspects meet the requirements of regulatory body. Work currently undertaken at Ontario Hydro Research Pump Test Complex on two-phase flow in pumps and piping may provide better prediction of vibration characteristics so that inherent conservativeness in fatigue Life prediction of HI system components can be reduced.

  1. Design retrofit to prevent damage due to heat transport pump operation under conditions of significant void

    International Nuclear Information System (INIS)

    Lam, K.F.

    1991-01-01

    The purpose of this paper is to provide a general review of certain key design areas which address the safety concerns of HT pump operation under conditions of significant void. To illustrate the challenges confronting designers and analysts, some of the highlights during the design of a protective system to prevent damage to HT piping and pump supports at Bruce NGS 'A' are outlined. The effects of this protective system on reactor safety are also discussed. HI pump operation under conditions of significant void offers a major challenge to designers and analysts to ensure that pump induced vibration and its effects on pump and piping are addressed. For an in-service station the search for a practical solution is often limited by existing. station equipment design and Layout. The diversity of design verification process requires a major commitment of engineering resources to ensure all. safety aspects meet the requirements of regulatory body. Work currently undertaken at Ontario Hydro Research Pump Test Complex on two-phase flow in pumps and piping may provide better prediction of vibration characteristics so that inherent conservativeness in fatigue Life prediction of HI system components can be reduced

  2. Dissociation of conditioned taste avoidance from conditioned disgust reactions induced by wheel running in rats.

    Science.gov (United States)

    Grant, Virginia L; McDonald, Sarah V; Sheppard, Robyn C; Caldwell, Catherine L; Heeley, Thomas H; Brown, Adam R; Martin, Gerard M

    2012-06-01

    It is well established that wheel running in rats produces conditioned taste avoidance; that is, rats that run in wheels after consuming a novel-tasting solution later consume less of that solution than rats that do not run. In experiment 1, we found that wheel running also produces conditioned disgust reactions, indicated by gapes elicited by both the taste and context that were experienced before running. Experiment 2 showed that the conditioned disgust reactions were likely not due to running itself but to a by-product of running, the rocking of the wheel that occurs when the running stops. When rocking was reduced, the disgust reactions were also reduced, but consumption of the taste solution was not changed, showing dissociation of conditioned taste avoidance and disgust. These findings indicate that the taste avoidance induced by wheel running itself is more like the taste avoidance produced by rewarding drugs than that produced by nausea-inducing drugs. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  3. HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions.

    Science.gov (United States)

    Tsuchida, Shinji; Arai, Yuji; Takahashi, Kenji A; Kishida, Tsunao; Terauchi, Ryu; Honjo, Kuniaki; Nakagawa, Shuji; Inoue, Hiroaki; Ikoma, Kazuya; Ueshima, Keiichiro; Matsuki, Tomohiro; Mazda, Osam; Kubo, Toshikazu

    2014-08-01

    We assessed whether heat shock protein 70 (HSP70) is involved in hypoxia inducible factor 1 alpha (HIF-1α)-dependent anabolic pathways in articular chondrocytes under hypoxic conditions. Primary rabbit chondrocytes were cultured under normoxia (20% oxygen condition) or hypoxia (1% oxygen condition). Alternatively, cells cultured under normoxia were treated with CoCl2 , which induces HIF-1α, to simulate hypoxia, or transfected with siRNAs targeting HIF-1α (si-HIF-1α) and HSP70 (si-HSP70) under hypoxia. HSP70 expression was enhanced by the increased expression of HIF-1α under hypoxia or simulated hypoxia, but not in the presence of si-HIF-1α. Hypoxia-induced overexpression of ECM genes was significantly suppressed by si-HIF-1α or si-HSP70. Cell viability positively correlated with hypoxia, but transfection with si-HIF-1α or si-HSP70 abrogated the chondroprotective effects of hypoxia. Although LDH release from sodium nitroprusside-treated cells and the proportion of TUNEL positive cells were decreased under hypoxia, transfection with si-HIF-1α or si-HSP70 almost completely blocked these effects. These findings indicated that HIF-1α-induced HSP70 overexpression increased the expression levels of ECM genes and cell viability, and protected chondrocytes from apoptosis. HIF-1α may regulate the anabolic effects of chondrocytes under hypoxic conditions by regulating HSP70 expression. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. Three-dimensional culture conditions lead to decreased radiation induced cytotoxicity in human mammary epithelial cells

    International Nuclear Information System (INIS)

    Sowa, Marianne B.; Chrisler, William B.; Zens, Kyra D.; Ashjian, Emily J.; Opresko, Lee K.

    2010-01-01

    For both targeted and non-targeted exposures, the cellular responses to ionizing radiation have predominantly been measured in two-dimensional monolayer cultures. Although convenient for biochemical analysis, the true interactions in vivo depend upon complex interactions between cells themselves and the surrounding extracellular matrix. This study directly compares the influence of culture conditions on radiation induced cytotoxicity following exposure to low-LET ionizing radiation. Using a three-dimensional (3D) human mammary epithelial tissue model, we have found a protective effect of 3D cell culture on cell survival after irradiation. The initial state of the cells (i.e., 2D versus 3D culture) at the time of irradiation does not alter survival, nor does the presence of extracellular matrix during and after exposure to dose, but long term culture in 3D which offers significant reduction in cytotoxicity at a given dose (e.g. ∼4-fold increased survival at 5 Gy). The cell cycle delay induced following exposure to 2 and 5 Gy was almost identical between 2D and 3D culture conditions and cannot account for the observed differences in radiation responses. However the amount of apoptosis following radiation exposure is significantly decreased in 3D culture relative to the 2D monolayer after the same dose. A likely mechanism of the cytoprotective effect afforded by 3D culture conditions is the down regulation of radiation induced apoptosis in 3D structures.

  5. Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

    Science.gov (United States)

    Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

    2017-02-15

    The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced

  6. Excitation of lateral habenula neurons as a neural mechanism underlying ethanol‐induced conditioned taste aversion

    Science.gov (United States)

    Keefe, Kristen A.; Taha, Sharif A.

    2016-01-01

    Key points The lateral habenula (LHb) has been implicated in regulation of drug‐seeking behaviours through aversion‐mediated learning.In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol‐induced conditioned taste aversion (CTA) to saccharin.Ethanol‐induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste.In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol‐induced CTA.Our results strongly suggest that excitation of LHb neurons is required for ethanol‐induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Abstract Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion‐mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol‐induced aversion, we recorded neural firing in the LHb of freely behaving, water‐deprived rats before and after an ethanol‐induced (1.5 g kg−1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol‐induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA

  7. Pseudomonas putida response in membrane bioreactors under salicylic acid-induced stress conditions

    Energy Technology Data Exchange (ETDEWEB)

    Collado, Sergio; Rosas, Irene; González, Elena; Gutierrez-Lavin, Antonio; Diaz, Mario, E-mail: mariodiaz@uniovi.es

    2014-02-01

    Highlights: • MBR under feed-induced stress conditions: starvation and changing feeding conditions. • High capacity of MBR to withstand high variations in feed loads. • Slow biofilm formation under starvation conditions during the first days. • Observed growth of P. putida for substrate to microorganism ratio higher than 0.6 g/g. • Maximum specific growth rate and growth yield values of around 37.5 h{sup −1} and 0.5 g/g. - Abstract: Starvation and changing feeding conditions are frequently characteristics of wastewater treatment plants. They are typical causes of unsteady-state operation of biological systems and provoke cellular stress. The response of a membrane bioreactor functioning under feed-induced stress conditions is studied here. In order to simplify and considerably amplify the response to stress and to obtain a reference model, a pure culture of Pseudomonas putida was selected instead of an activated sludge and a sole substrate (salicylic acid) was employed. The system degraded salicylic acid at 100–1100 mg/L with a high level of efficiency, showed rapid acclimation without substrate or product inhibition phenomena and good stability in response to unsteady states caused by feed variations. Under starvation conditions, specific degradation rates of around 15 mg/g h were achieved during the adaptation of the biomass to the new conditions and no biofilm formation was observed during the first days of experimentation using an initial substrate to microorganisms ratio lower than 0.1. When substrate was added to the reactor as pulses resulting in rapidly changing concentrations, P. putida growth was observed only for substrate to microorganism ratios higher than 0.6, with a maximum Y{sub X/S} of 0.5 g/g. Biofilm development under changing feeding conditions was fast, biomass detachment only being significant for biomass concentrations on the membrane surface that were higher than 16 g/m{sup 2}.

  8. Pseudomonas putida response in membrane bioreactors under salicylic acid-induced stress conditions

    International Nuclear Information System (INIS)

    Collado, Sergio; Rosas, Irene; González, Elena; Gutierrez-Lavin, Antonio; Diaz, Mario

    2014-01-01

    Highlights: • MBR under feed-induced stress conditions: starvation and changing feeding conditions. • High capacity of MBR to withstand high variations in feed loads. • Slow biofilm formation under starvation conditions during the first days. • Observed growth of P. putida for substrate to microorganism ratio higher than 0.6 g/g. • Maximum specific growth rate and growth yield values of around 37.5 h −1 and 0.5 g/g. - Abstract: Starvation and changing feeding conditions are frequently characteristics of wastewater treatment plants. They are typical causes of unsteady-state operation of biological systems and provoke cellular stress. The response of a membrane bioreactor functioning under feed-induced stress conditions is studied here. In order to simplify and considerably amplify the response to stress and to obtain a reference model, a pure culture of Pseudomonas putida was selected instead of an activated sludge and a sole substrate (salicylic acid) was employed. The system degraded salicylic acid at 100–1100 mg/L with a high level of efficiency, showed rapid acclimation without substrate or product inhibition phenomena and good stability in response to unsteady states caused by feed variations. Under starvation conditions, specific degradation rates of around 15 mg/g h were achieved during the adaptation of the biomass to the new conditions and no biofilm formation was observed during the first days of experimentation using an initial substrate to microorganisms ratio lower than 0.1. When substrate was added to the reactor as pulses resulting in rapidly changing concentrations, P. putida growth was observed only for substrate to microorganism ratios higher than 0.6, with a maximum Y X/S of 0.5 g/g. Biofilm development under changing feeding conditions was fast, biomass detachment only being significant for biomass concentrations on the membrane surface that were higher than 16 g/m 2

  9. Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

    Science.gov (United States)

    Hess, M W; de Baaij, J H F; Broekman, M; Bisseling, T M; Haarhuis, B; Tan, A; Te Morsche, R; Hoenderop, J G J; Bindels, R J M; Drenth, J P H

    2016-06-01

    Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia. © 2016 John Wiley & Sons Ltd.

  10. Extreme Changes in Stream Geomorphic Conditions induced by Fluvial Scour in Bridges

    Science.gov (United States)

    Özcan, O.; Ozcan, O.

    2016-12-01

    The numerous complexities associated with bridge scour have caused scour to be one of the most active topics of stream geomorphic research. The assessment of local scouring mechanism around bridge piers provides information for decision-making regarding the pile footing design, predicting the safety of bridges under critical scoured conditions, and as a result, may help prevent unnecessary loses. In the study, bridge design plans and HEC-RAS modeling were used for the assessment of changes in stream geomorphic conditions. The derived fluvial scour depths were compared with the field measurements and the empirical formula which is based on stream flow discharge rate, streambed condition and shape of river. Preliminary results revealed that bridge damage resulting from the flood event in 2003 induced substantial scour around bridge piles. Afterwards, significant stream bed change was observed under the influence of fluvial scour in another flood occurred in 2009. Consequently, geomorphic conditions of the stream bed should be considered in the structural design of the bridges.

  11. Machine Induced Experimental Background Conditions in the LHC

    CERN Document Server

    Levinsen, Yngve Inntjore; Stapnes, Steinar

    2012-09-19

    The Large Hadron Collider set a new energy record for particle accelerators in late 2009, breaking the previous record held by Tevatron of 2 TeV collision energy. The LHC today operates at a collision energy of 7 TeV. With higher beam energy and intensity, measures have to be taken to ensure optimal experimental conditions and safety of the machine and detectors. Machine induced experimental background can severely reduce the quality of experimental triggers and track reconstruction. In a worst case, the radiation levels can be damaging for some of the subdetectors. The LHC is a particular challenge in this regard due to the vastly different operating conditions of the different experiments. The nominal luminosity varies by four orders of magnitude. The unprecedented stored beam energy and the amount of superconducting elements can make it challenging to protect the accelerator itself as well. In this work we have simulated and measured the machine induced background originating from various sources: the beam...

  12. Enhancement of acetylcholine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

    Science.gov (United States)

    Horio, S; Nagare, T; Moritoki, H

    1999-10-01

    1. To determine the role of cellular Ca2+ in desensitization, acetylcholine(ACh)-induced desensitization was studied under Ca2+-free condition in guinea-pig ileal longitudinal muscle. 2. Pretreatment of the tissue with 10(-4) M ACh (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses both to ACh and histamine. The desensitizing treatment performed in Ca2+-free solution enhanced desensitization of the responses to ACh and histamine significantly. 3. The desensitizing treatment with ACh caused suppression of the responses to high K+ (tonic component) and Bay K 8644. The desensitizing treatment performed in Ca2+-free solution potentiated the suppression of the responses to high K+ and Bay K 8644 significantly. 4. ACh-induced desensitization was enhanced significantly in the presence of a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7, 10(-4) M) to a similar extent as desensitization obtained under Ca2+-free condition, but not in the presence of a non-specific and less potent kinase inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 10(-4) M). 5. These results suggested that voltage-gated Ca2+ channels were involved in ACh-induced desensitization and that intracellular Ca2+, which was increased during the stimulation with ACh, inhibited desensitization through the activation of protein kinase C. This kinase could have activated or protected Ca2+ channels during the desensitization process to reduce desensitization.

  13. Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance

    International Nuclear Information System (INIS)

    Hunt, W.A.; Rabin, B.M.

    1988-01-01

    An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself

  14. Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

    Science.gov (United States)

    Feng, Linjie; Gan, Hongquan; Zhao, Wenguo; Liu, Yingjie

    2017-01-01

    Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium-induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium-treated group; group B, normal BMSC-treated group; group C, OEC conditioned medium-induced BMSC-treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein-43 and neuron-specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results. PMID:28656221

  15. Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition.

    Science.gov (United States)

    Song, Juhyun; Kim, Oh Yoen

    2017-06-10

    Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, p-IRE1 , and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1 . The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 ( p-ASK1 ) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

  16. Changes of fatty acid aerosol hygroscopicity induced by ozonolysis under humid conditions

    Directory of Open Access Journals (Sweden)

    O. Vesna

    2008-08-01

    Full Text Available Unsaturated fatty acids are important constituents of the organic fraction of atmospheric aerosols originating from biogenic or combustion sources. Oxidative processing of these may change their interaction with water and thus affect their effect on climate. The ozonolysis of oleic and arachidonic acid aerosol particles was studied under humid conditions in a flow reactor at ozone exposures close to atmospheric levels, at concentrations between 0.5 and 2 ppm. While oleic acid is a widely used proxy for such studies, arachidonic acid represents polyunsaturated fatty acids, which may decompose into hygroscopic products. The hygroscopic (diameter growth factor at 93% relative humidity (RH of the oxidized arachidonic particles increased up to 1.09 with increasing RH during the ozonolysis. In contrast, the growth factor of oleic acid was very low (1.03 at 93% RH and was almost invariant to the ozonolysis conditions, so that oleic acid is not a good model to observe oxidation induced changes of hygroscopicity under atmospheric conditions. We show for arachidonic acid particles that the hygroscopic changes induced by humidity during ozonolysis are accompanied by about a doubling of the ratio of carboxylic acid protons to aliphatic protons. We suggest that, under humid conditions, the reaction of water with the Criegee intermediates might open a pathway for the formation of smaller acids that lead to more significant changes in hygroscopicity. Thus the effect of water to provide a competing pathway during ozonolysis observed in this study should be motivation to include water, which is ubiquitously present in and around atmospheric particles, in future studies related to aerosol particle aging.

  17. Transcriptome analysis documents induced competence of Bacillus subtilis during nitrogen limiting conditions

    DEFF Research Database (Denmark)

    Jarmer, Hanne Østergaard; Berka, R.; Knudsen, Steen

    2002-01-01

    DNA microarrays were used to analyze the changes in gene expression in Bacillus subtilis strain 168 when nitrogen limiting (glutamate) and nitrogen excess (ammonium plus glutamate) growth conditions were compared. Among more than 100 genes that were significantly induced during nitrogen starvation...... we detected the comG, comF, comE, nin-nucA and comK transcription units together with recA. DNA was added to B. subtilis grown in minimal medium with glutamate as the sole nitrogen source and it was demonstrated that the cells were competent. Based on these observations we propose a simplification...

  18. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  19. Attenuation of radiation- and drug-induced conditioned taste aversions following area postrema lesions in the rat

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1983-01-01

    The effects of lesions of the area postrema on the acquisition of radiation- and drug-induced (histamine and lithium chloride) conditioned taste aversions were investigated. The results indicated that area postrema lesions caused a significant attenuation of the aversion produced by pairing a novel sucrose solution with radiation (100 rad) or drug injection. Further, the area postrema lesions produced a similar level of attenuation of the taste aversion in all three treatment conditions. The results are discussed in terms of the implications of this finding for defining the mechanisms by which exposure to ionizing radiation can lead to the acquisition of a conditioned taste aversion

  20. Effect of surface wettability caused by radiation induced surface activation on leidenfrost condition

    International Nuclear Information System (INIS)

    Takamasa, T.; Hazuku, T.; Tamura, N.; Okamoto, K.; Mishima, K.; Furuya, M.

    2003-01-01

    Improving the limit of boiling heat transfer or critical heat flux requires that the cooling liquid can contact the heating surface, or a high-wettability, highly hydrophilic heating surface, even if a vapor bubble layer is generated on the surface. From this basis, we investigated surface wettability and Leidenfrost condition using metal oxides irradiated by γ-rays. In our previous study, contact angle, an indicator of macroscopic wettability, of a water droplet on metal oxide at room temperature was measured by image processing of the images obtained by a CCD video camera. The results showed that the surface wettability on metal oxide pieces of titanium, Zircaloy No. 4, SUS-304, and copper was improved significantly by the Radiation Induced Surface Activation (RISA) phenomenon. To delineate the effect of Radiation Induced Surface Activation (RISA) on heat transferring phenomena, the Leidenfrost condition and quenching of metal oxides irradiated by γ-rays were investigated. In the Leidenfrost experiment, when the temperature of the heating surface reached the wetting limit temperature, water-solid contact vanished because a stable vapor film existed between the droplet and the metal surface; i.e., a Leidenfrost condition obtained. The wetting limit temperature increased with integrated irradiation dose. After irradiation, the wet length and the duration of contact increased, and the contact angle decreased. In the quenching test, high surface wettability, or a highly hydrophilic condition, of a simulated fuel rod made of SUS was achieved, and the quenching velocities were increased up to 20-30% after 300 kGy 60Co γ-ray irradiation

  1. Effect of surface wettability caused by radiation induced surface activation on leidenfrost condition

    Energy Technology Data Exchange (ETDEWEB)

    Takamasa, T.; Hazuku, T.; Tamura, N.; Okamoto, K. [Tokyo Univ., Tokyo (Japan); Mishima, K. [Kyoto Univ., Kyoto (Japan); Furuya, M. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    2003-07-01

    Improving the limit of boiling heat transfer or critical heat flux requires that the cooling liquid can contact the heating surface, or a high-wettability, highly hydrophilic heating surface, even if a vapor bubble layer is generated on the surface. From this basis, we investigated surface wettability and Leidenfrost condition using metal oxides irradiated by {gamma}-rays. In our previous study, contact angle, an indicator of macroscopic wettability, of a water droplet on metal oxide at room temperature was measured by image processing of the images obtained by a CCD video camera. The results showed that the surface wettability on metal oxide pieces of titanium, Zircaloy No. 4, SUS-304, and copper was improved significantly by the Radiation Induced Surface Activation (RISA) phenomenon. To delineate the effect of Radiation Induced Surface Activation (RISA) on heat transferring phenomena, the Leidenfrost condition and quenching of metal oxides irradiated by {gamma}-rays were investigated. In the Leidenfrost experiment, when the temperature of the heating surface reached the wetting limit temperature, water-solid contact vanished because a stable vapor film existed between the droplet and the metal surface; i.e., a Leidenfrost condition obtained. The wetting limit temperature increased with integrated irradiation dose. After irradiation, the wet length and the duration of contact increased, and the contact angle decreased. In the quenching test, high surface wettability, or a highly hydrophilic condition, of a simulated fuel rod made of SUS was achieved, and the quenching velocities were increased up to 20-30% after 300 kGy 60Co {gamma}-ray irradiation.

  2. The meninges contribute to the conditioned taste avoidance induced by neural cooling in male rats.

    Science.gov (United States)

    Wang, Yuan; Chambers, Kathleen C

    2002-08-21

    After consumption of a novel sucrose solution, temporary cooling of neural areas that mediate conditioned taste avoidance can itself induce conditioned avoidance to the sucrose. It has been suggested that this effect is either a result of inactivation of neurons in these areas or of cooling the meninges. In a series of studies, we demonstrated that cooling the outer layer of the meninges, the dura mater, does not contribute to the conditioned taste avoidance induced by cooling any of these areas. The present experiments were designed to determine whether the inner layers of the meninges are involved. If they are involved, then one would expect that cooling locations in the brain that do not mediate conditioned taste avoidance, such as the caudate putamen (CP), would induce conditioned taste avoidance as long as the meninges were cooled as well. One also would expect that cooling neural tissue without cooling the meninges would reduce the strength of the conditioned taste avoidance. Experiment 1 established that the temperature of the neural tissue and meninges around the cold probes implanted in the CP were cooled to temperatures that have been shown to block synaptic transmission. Experiment 2 demonstrated that cooling the caudate putamen and overlying cortex and meninges induced conditioned taste avoidance. In experiment 3, a circle of meninges was cut away so that the caudate putamen and overlying cortex could be cooled without cooling the meninges. The strength of the conditioned taste avoidance was substantially reduced, but it was not entirely eliminated. These data support the hypothesis that cooling the meninges contributes to the conditioned taste avoidance induced by neural cooling. They also allow the possibility that neural inactivation produces physiological changes that can induce conditioned taste avoidance. Copyright 2002 Elsevier Science B.V.

  3. One arm exercise induces significant interarm diastolic blood pressure difference.

    Science.gov (United States)

    Hong, Dezhi; Wang, Jiwei; Su, Hai; Xu, Jingsong; Liu, Yanna; Peng, Qiang; Wang, Lijuan

    2011-06-01

    This study is designed to investigate the inducing effect of one arm exercise on interarm difference (IAD) in the blood pressure (BP). Fifty healthy young participants were included in the study. Three-minute exercises of the right arm elbow flexion and extension were performed. The bilateral brachial BP was simultaneously measured with two automatic BP measurement devices before (basic) and immediately 0, 5, 10, 15, 20, and 30 min after exercise. The absolute difference in the systolic BP (SBP) and diastolic BP (DBP) between the left and right BP of at least 10 mmHg was recognized as sIAD and dIAD. The baseline data of the SBP and DBP in left and right arms revealed no significant difference (SBP: 110 ± 10 vs. 111 ± 11 mmHg; DBP: 66 ± 8 vs. 66 ± 9 mmHg, both not significant). The prevalence of dIAD was 2% at the baseline. However, this prevalence increased to 80% at 0 min, as right arm exercise induced the right DBP decrease and left DBP increase, and then the prevalence decreased gradually within a 30-min recovery period. The prevalence of sIAD was zero at the baseline and the maximal prevalence was 8% during the 20-min postexercise period. One arm exercise can lead to a significant IAD in DBP. Any arm exercise should be avoided before BP measurement.

  4. Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats.

    Science.gov (United States)

    Rock, E M; Parker, L A

    2013-06-01

    To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND). We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined. CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping. CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  5. Age and gender differences in mechanically induced intraoral temporal summation and conditioned pain modulation in healthy subjects.

    Science.gov (United States)

    Khan, Junad; Korczeniewska, Olga; Benoliel, Rafael; Kalladka, Mythili; Eliav, Eli; Nasri-Heir, Cibelle

    2018-04-13

    The aim of this study was to investigate intraoral temporal summation (TS) and conditioned pain modulation (CPM) and compare the outcome with TS and CPM induced in the forearm. In addition, we aimed to study the effect of age and gender on intraoral and forearm TS and CPM. Mechanical stimulation was induced with # 5.46 von Frey filament applying 26 grams of force. A single stimulus, followed by a train of 30 successive stimuli, was applied intraorally and to the dominant forearm. CPM was assessed with the TS test as the painful stimulus and with immersion of the nondominant hand in a hot water bath as the conditioning stimulus. Gender was significantly associated with TS but not with CPM measures. Females had significantly lower mean TS measured in the face and in the dominant forearm compared with males. Age was significantly associated with CPM, but not with TS measures. In both sites examined, older patients had significantly lower mean CPM compared with younger patients. Mechanical TM elicited in the oral cavity can be used as test stimulus for CPM testing. Intraoral modulation, both TS and CPM, has an extent similar to that of the standard cutaneous extremity. TS was lower in females, and CPM was reduced with age. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.

    Directory of Open Access Journals (Sweden)

    Andrew K Haack

    Full Text Available The lateral habenula (LHb plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

  7. Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion.

    Science.gov (United States)

    Kim, Kyu-Nam; Kim, Bom-Taeck; Kim, Young-Sang; Lee, Jong-Ho; Jahng, Jeong Won

    2014-05-05

    Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Significance levels for studies with correlated test statistics.

    Science.gov (United States)

    Shi, Jianxin; Levinson, Douglas F; Whittemore, Alice S

    2008-07-01

    When testing large numbers of null hypotheses, one needs to assess the evidence against the global null hypothesis that none of the hypotheses is false. Such evidence typically is based on the test statistic of the largest magnitude, whose statistical significance is evaluated by permuting the sample units to simulate its null distribution. Efron (2007) has noted that correlation among the test statistics can induce substantial interstudy variation in the shapes of their histograms, which may cause misleading tail counts. Here, we show that permutation-based estimates of the overall significance level also can be misleading when the test statistics are correlated. We propose that such estimates be conditioned on a simple measure of the spread of the observed histogram, and we provide a method for obtaining conditional significance levels. We justify this conditioning using the conditionality principle described by Cox and Hinkley (1974). Application of the method to gene expression data illustrates the circumstances when conditional significance levels are needed.

  9. Single Prazosin Infusion in Prelimbic Cortex Fosters Extinction of Amphetamine-Induced Conditioned Place Preference

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    Emanuele C. Latagliata

    2017-08-01

    Full Text Available Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP. A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS. Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor (BDNF and post-synaptic density 95 (PSD-95 in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic

  10. Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

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    Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

    2004-01-01

    The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

  11. Pre-existing Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced BRONJ Lesions in Mice

    Science.gov (United States)

    Song, Minju; Alshaikh, Abdullah; Kim, Terresa; Kim, Sol; Dang, Michelle; Mehrazarin, Shebli; Shin, Ki-Hyuk; Kang, Mo; Park, No-Hee; Kim, Reuben H.

    2016-01-01

    Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ. PMID:27637460

  12. Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions.

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    Zhang, Feng-Lin; Shen, Guo-Min; Liu, Xiao-Ling; Wang, Fang; Zhao, Ying-Ze; Zhang, Jun-Wu

    2012-08-01

    Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type-specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34(+) haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl(2) induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1-mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  13. Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

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    Raphaël Millière

    2017-05-01

    Full Text Available There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR. While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves

  14. Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

    Science.gov (United States)

    Millière, Raphaël

    2017-01-01

    There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On

  15. Conditioned medium from alternatively activated macrophages induce mesangial cell apoptosis via the effect of Fas

    International Nuclear Information System (INIS)

    Huang, Yuan; Luo, Fangjun; Li, Hui; Jiang, Tao; Zhang, Nong

    2013-01-01

    During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions. - Highlights: • Conditioned-medium from M2 macrophages induces rat mesangial cell (MsC) apoptosis. • M2 macrophage conditioned medium exerts its pro-apoptotic effects via Fas ligand. • Arginase-1 activity in M2 macrophages plays a role in inducing apoptosis in rat MsC

  16. Conditioned medium from alternatively activated macrophages induce mesangial cell apoptosis via the effect of Fas

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    Huang, Yuan; Luo, Fangjun; Li, Hui; Jiang, Tao; Zhang, Nong, E-mail: nzhang@fudan.edu.cn

    2013-11-15

    During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions. - Highlights: • Conditioned-medium from M2 macrophages induces rat mesangial cell (MsC) apoptosis. • M2 macrophage conditioned medium exerts its pro-apoptotic effects via Fas ligand. • Arginase-1 activity in M2 macrophages plays a role in inducing apoptosis in rat MsC.

  17. Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

    Science.gov (United States)

    Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

    2017-06-01

    Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and conditioned place preference in mice.

    Science.gov (United States)

    Zambrana-Infantes, Emma; Rosell Del Valle, Cristina; Ladrón de Guevara-Miranda, David; Galeano, Pablo; Castilla-Ortega, Estela; Rodríguez De Fonseca, Fernando; Blanco, Eduardo; Santín, Luis Javier

    2018-03-01

    Cocaine addiction is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors. Previous studies have demonstrated that cocaine, as well as other drugs of abuse, alters the levels of lipid-based signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels of NAEs have shown sensitivity to cocaine self-administration and extinction training in rodents. Given this background, the aim of this study was to investigate the effects of repeated or acute administration of palmitoylethanolamide (PEA), an endogenous NAE, on psychomotor sensitization and cocaine-induced contextual conditioning. To this end, the potential ability of repeated PEA administration (1 or 10 mg/kg, i.p.) to modulate the acquisition of cocaine-induced behavioral sensitization (BS) and conditioned place preference (CPP) was assessed in male C57BL/6J mice. In addition, the expression of cocaine-induced BS and CPP following acute PEA administration were also studied. Results showed that repeated administration of both doses of PEA were able to block the acquisition of cocaine-induced BS. Furthermore, acute administration of both doses of PEA was able to abolish the expression of BS, while the highest dose also abolished the expression of cocaine-induced CPP. Taken together, these results indicate that exogenous administration of PEA attenuated psychomotor sensitization, while the effect of PEA in cocaine-induced CPP depended on whether PEA was administered repeatedly or acutely. These findings could be relevant to understand the role that NAEs play in processes underlying the development and maintenance of cocaine addiction. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Knockdown of hypoxia-inducible factor-1 alpha reduces proliferation, induces apoptosis and attenuates the aggressive phenotype of retinoblastoma WERI-Rb-1 cells under hypoxic conditions.

    Science.gov (United States)

    Xia, Tian; Cheng, Hao; Zhu, Yu

    2014-01-01

    Hypoxia-inducible factor-1 alpha (HIF-1α) plays a critical role in tumor cell adaption to hypoxia by inducing the transcription of numerous genes. The role of HIF-1α in malignant retinoblastoma remains unclear. We analyzed the role of HIF-1α in WERI-Rb-1 retinoblastoma cells under hypoxic conditions. CoCl2 (125 mmol/L) was added to the culture media to mimic hypoxia. HIF-1α was silenced using siRNA. Gene and protein expression were measured by semi-quantitative RT-PCR and Western blotting. Cell cycle and apoptosis were analyzed by flow cytometry. Cell proliferation, adhesion and invasion were assayed using MTT, Transwell invasion, and cell adhesion assays respectively. Hypoxia significantly upregulated HIF-1α protein expression and the HIF-1α target genes VEGF, GLUT1, and Survivin mRNA. HIF-1α mRNA expression was not affected by hypoxia. Transfection of the siRNA expression plasmid pRNAT-CMV3.2/Neo-HIF-1α silenced HIF-1α by approximately 80% in hypoxic WERI-Rb-1 cells. The knockdown of HIF-1α under hypoxic conditions downregulated VEGF, GLUT1, and Survivin mRNA. It also inhibited proliferation, promoted apoptosis, induced the G0/G1 phase cell cycle arrest, and reduced the adhesion and invasion of WERI-Rb-1 cells. HIF-1α plays a major role in the survival and aggressive phenotype of retinoblastoma cells under hypoxic conditions. Targeting HIF-1α may be a promising therapeutic strategy for human malignant retinoblastoma.

  20. Drug-induced conditioned place preference and aversion in mice.

    Science.gov (United States)

    Cunningham, Christopher L; Gremel, Christina M; Groblewski, Peter A

    2006-01-01

    This protocol describes the equipment and methods used to establish conditioned place preference (CPP) or aversion (CPA). Place conditioning is a form of Pavlovian conditioning routinely used to measure the rewarding or aversive motivational effects of objects or experiences (e.g., abused drugs). Here, we present a place conditioning procedure that has been used extensively to study the motivational effects of ethanol and other abused drugs in mice. This protocol involves three phases: (i) habituation (or a pretest), (ii) conditioning of an association between the drug and a tactile or visual stimulus and (iii) a test that offers a choice between the drug-associated cue and a neutral cue. If the drug has motivational significance, mice will spend significantly more time (CPP) or less time (CPA) in proximity to the drug-associated cue. Potential problems in the design and interpretation of place conditioning studies are discussed. A typical experiment lasts 2 weeks.

  1. A novel strategy to identify the critical conditions for growth-induced instabilities.

    Science.gov (United States)

    Javili, A; Steinmann, P; Kuhl, E

    2014-01-01

    Geometric instabilities in living structures can be critical for healthy biological function, and abnormal buckling, folding, or wrinkling patterns are often important indicators of disease. Mathematical models typically attribute these instabilities to differential growth, and characterize them using the concept of fictitious configurations. This kinematic approach toward growth-induced instabilities is based on the multiplicative decomposition of the total deformation gradient into a reversible elastic part and an irreversible growth part. While this generic concept is generally accepted and well established today, the critical conditions for the formation of growth-induced instabilities remain elusive and poorly understood. Here we propose a novel strategy for the stability analysis of growing structures motivated by the idea of replacing growth by prestress. Conceptually speaking, we kinematically map the stress-free grown configuration onto a prestressed initial configuration. This allows us to adopt a classical infinitesimal stability analysis to identify critical material parameter ranges beyond which growth-induced instabilities may occur. We illustrate the proposed concept by a series of numerical examples using the finite element method. Understanding the critical conditions for growth-induced instabilities may have immediate applications in plastic and reconstructive surgery, asthma, obstructive sleep apnoea, and brain development. © 2013 Elsevier Ltd. All rights reserved.

  2. Reversal effect of intra-central amygdala microinjection of L-arginine on place aversion induced by naloxone in morphine conditioned rats.

    Science.gov (United States)

    Karimi, Sara; Karami, Manizheh; Sahraei, Hedayat; Rahimpour, Mahnaz

    2011-01-01

    Role of nitric oxide (NO) on expression of morphine conditioning using a solely classic task has been proposed previously. In this work, the involvement of NO on the expression of opioid-induced conditioning in the task paired with an injection of naloxone was investigated. Conditioning was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Naloxone (0.05-0.4 mg/kg, i.p.), a selective antagonist of mu-opioid receptor, was administered once prior to morphine response testing. NO agents were administered directly into the central amygdala (CeA) prior to naloxone injection pre-testing. Morphine (2.5-10 mg/kg, s.c.) produced a significant dose-dependent place preference in experimental animals. When naloxone (0.05-0.4 mg/kg, i.p.) was injected before testing of morphine (5 mg/kg, s.c.) response, the antagonist induced a significant aversion. This response was reversed due to injection of L-arginine (0.3-3 microg/rat), intra-CeA prior to naloxone administration. However, pre-injection of L-NAME (intra-CeA), an inhibitor of NO production, blocked this effect. The finding may reflect that NO in the nucleus participates in morphine plus naloxone interaction.

  3. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Science.gov (United States)

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  4. Conditioned Media from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Umbilical Cord-Derived Mesenchymal Stem Cells Efficiently Induced the Apoptosis and Differentiation in Human Glioma Cell Lines In Vitro

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2014-01-01

    Full Text Available Human mesenchymal stem cells (MSCs have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs. We found (1 MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2 MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3 real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4 furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.

  5. Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2008-01-01

    Full Text Available The conditioned place preference (CPP model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

  6. Evaluation of a nanotechnology-based approach to induce gene-expression in human THP-1 macrophages under inflammatory conditions.

    Science.gov (United States)

    Bernal, Laura; Alvarado-Vázquez, Abigail; Ferreira, David Wilson; Paige, Candler A; Ulecia-Morón, Cristina; Hill, Bailey; Caesar, Marina; Romero-Sandoval, E Alfonso

    2017-02-01

    Macrophages orchestrate the initiation and resolution of inflammation by producing pro- and anti-inflammatory products. An imbalance in these mediators may originate from a deficient or excessive immune response. Therefore, macrophages are valid therapeutic targets to restore homeostasis under inflammatory conditions. We hypothesize that a specific mannosylated nanoparticle effectively induces gene expression in human macrophages under inflammatory conditions without undesirable immunogenic responses. THP-1 macrophages were challenged with lipopolysaccharide (LPS, 5μg/mL). Polyethylenimine (PEI) nanoparticles grafted with a mannose receptor ligand (Man-PEI) were used as a gene delivery method. Nanoparticle toxicity, Man-PEI cellular uptake rate and gene induction efficiency (GFP, CD14 or CD68) were studied. Potential immunogenic responses were evaluated by measuring the production of tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6 and IL-10. Man-PEI did not produce cytotoxicity, and it was effectively up-taken by THP-1 macrophages (69%). This approach produced a significant expression of GFP (mRNA and protein), CD14 and CD68 (mRNA), and transiently and mildly reduced IL-6 and IL-10 levels in LPS-challenged macrophages. Our results indicate that Man-PEI is suitable for inducing an efficient gene overexpression in human macrophages under inflammatory conditions with limited immunogenic responses. Our promising results set the foundation to test this technology to induce functional anti-inflammatory genes. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. Role of hypoxia and hypoxia inducible factor in physiological and pathological conditions

    Directory of Open Access Journals (Sweden)

    Mozhgan Jahani

    2017-11-01

    Full Text Available Introduction: Organisms are exposed to oxygen deprivation (Hypoxia in various physiological and pathological conditions. There are different conserve evolutionary responses to counterview with this stress that primary transcriptional response to stress related to hypoxia is interceded by hypoxia-inducible factor (HIF-1 in mammals. This factor can regulate different genes that have essential roles in adaptation to this condition. In this review, the role of this factor in physiological and pathological conditions under hypoxic condition has been evaluated after examining structural features and regulation characteristics of HIF-1. Methods: First, articles related to the keywords of hypoxia and HIF-1 (from 1991-2016 were searched from valid databases such as Springer Link, Google Scholar, PubMed and Science direct. Then, the articles correlated with hypoxia, HIF-1 and their roles in physiological and pathological conditions (120 articles were searched and just 64 articles were selected for this study. Result: According to studies, there are different genes in cells and organs that can be regulated by HIF-1. Activation of genes expression by this protein occurs through its linkage to cis-acting of 50 base pair hypoxia response element (HRE region located in their promotor and enhancer. Depending on circumstances, activation of these genes can be beneficial or harmful. Conclusion: Activation of different genes in hypoxia by HIF-1 has different effects on physiological and pathological conditions. Therefore, HIF-1, as a hypoxia-inducible factor in hypoxic conditions, plays an essential role in the adaptation of cells and organs to changes related to the presence of oxygen.

  8. Vacuolar H+ -ATPase c protects glial cell death induced by sodium nitroprusside under glutathione-depleted condition.

    Science.gov (United States)

    Byun, Yu Jeong; Lee, Seong-Beom; Lee, Hwa Ok; Son, Min Jeong; Kim, Ho-Shik; Kwon, Oh-Joo; Jeong, Seong-Whan

    2011-08-01

    We examined the role of the c subunit (ATP6L) of vacuolar H(+) -ATPase and its molecular mechanisms in glial cell death induced by sodium nitroprusside (SNP). ATP6L siRNA-transfected cells treated with SNP showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, but reduction of ATP6L did not affect the regulation of lysosomal pH in analyses with lysosomal pH-dependent fluorescence probes. Photodegraded SNP and ferrous sulfate induced cytotoxicity with the same pattern as that of SNP, but SNAP and potassium cyanide did not show activity. Pretreatment of the transfected cells with deferoxamine (DFO) reduced ROS production and significantly inhibited the cytotoxicity, which indicates that primarily iron rather than nitric oxide or cyanide from SNP contributes to cell death. Involvement of apoptotic processes in the cells was not shown. Pretreatment with JNK or p38 chemical inhibitor significantly inhibited the cytotoxicity, and we also confirmed that the MAPKs were activated in the cells by immunoblot analysis. Significant increase of LC3-II conversion was observed in the cells, and the conversions were inhibited by cotransfection of the MAPK siRNAs and pretreatment with DFO. Introduction of Atg5 siRNA inhibited the cytotoxicity and inhibited the activation of MAPKs and the conversion of LC3. We finally confirmed autophagic cell death and involvement of MAPKs by observation of autophagic vacuoles via electron microscopy. These data suggest that ATP6L has a protective role against SNP-induced autophagic cell death via inhibition of JNK and p38 in GSH-depleted glial cells. Copyright © 2011 Wiley-Liss, Inc.

  9. Enhancement in irradiated mononuclear cells in culture of mitogen-induced incorporation of [3H]thymidine by homologous conditioned medium

    International Nuclear Information System (INIS)

    Sandru, G.; Greiner, R.

    1994-01-01

    Incorporation of [ 3 H]thymidine in irradiated peripheral blood mononuclear cell cultures irradiated in vitro was stimulated significantly by either concanavalin A or phytohemagglutinin only in the presence of homologous conditioned medium. Production of this activity by mononuclear cells was enhanced by irradiation and/or pulsed exposure to puromycin but was abolished by actinomycin D. Addition of anti-interleukin 1 or anti-interleukin 2 monoclonal antibodies to the conditioned medium before assay did not influence the stimulatory action. A similar significant stimulation of mononuclear cell cultures irradiated with 6 Gy by concanavalin A was obtained when purified preparations of homologous conditioned medium were used in the assay. Purification was done by ultrafiltration and concentration, heparin agarose chromatography, ammonium sulfate precipitation, concanavalin A agarose chromatography, DEAE-ion exchange chromatography and HPLC gel filtration chromatography. With SDS-PAGE and silver staining, the active HPLC fraction gave one band of 50 kDa, suggesting that this protein is responsible for the co-stimulatory effect of homologous conditioned medium for both mitogen-induced irradiated and nonirradiated mononuclear cell cultures. 42 refs., 9 figs., 3 tabs

  10. The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned place preference and physical dependence.

    Science.gov (United States)

    Alavi, Mohaddeseh Sadat; Hosseinzadeh, Hossein; Shamsizadeh, Ali; Roohbakhsh, Ali

    2016-06-01

    Previous studies show that some non-CB1/non-CB2 effects of cannabinoids are mediated through G protein coupled receptor 55 (GPR55). As this receptor is activated by some of cannabinoid receptor ligands and is involved in the modulation of pain, it was hypothesized that this receptor may also interact with opioids. This study examined the effect of atypical cannabinoid O-1602 as a GPR55 agonist on morphine-induced conditioned place preference (CPP) and physical dependence. We used a biased CPP model to evaluate the effect of O-1602 (0.2, 1 and 5mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP in male mice. The locomotor activities of mice were also recorded. Moreover, repeated administration of morphine (50, 50 and 75mg/kg/day) for three days, induced physical dependence. The withdrawal signs such as jumps and diarrhea were precipitated by administration of naloxone (5mg/kg, ip). The effect of O-1602 on the development of morphine physical dependence was assessed by injection of O-1602 (0.2, 1 and 5mg/kg) before morphine administrations. Morphine (40mg/kg, subcutaneous; sc), but not O-1602 (5mg/kg) elicited significant preference in the post-conditioning phase. O-1602 at the doses of 0.2 and 1mg/kg, but not 5mg/kg reduced acquisition of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 at the doses of 0.2, 1 and 5mg/kg also reduced expression of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 had a significant inhibitory effect on development of morphine-induced physical dependence at the dose of 5mg/kg by decreasing jumps and diarrhea during withdrawal syndrome. The present results indicate that O-1602 decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Transgenic mice for a tamoxifen-induced, conditional expression of the Cre recombinase in osteoclasts.

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    Maria Arantzazu Sanchez-Fernandez

    Full Text Available BACKGROUND: Studies on osteoclasts, the bone resorbing cells, have remained limited due to the lack of transgenic mice allowing the conditional knockout of genes in osteoclasts at any time during development or adulthood. METHODOLOGY/PRINCIPAL FINDING: We report here on the generation of transgenic mice which specifically express a tamoxifen-inducible Cre recombinase in osteoclasts. These mice, generated on C57BL/6 and FVB background, express a fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of cathepsin K (CtsK, a gene highly expressed in osteoclasts. We tested the cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ positive adult mice and E17.5 embryos show that Cre activity is restricted largely to bone tissue. In vitro, primary osteoclasts derived from the bone marrow of CtsKCreERT2+/-LacZ+/- adult mice show a Cre-dependent β-galactosidase activity after tamoxifen stimulation. CONCLUSIONS/SIGNIFICANCE: We have generated transgenic lines that enable the tamoxifen-induced, conditional deletion of loxP-flanked genes in osteoclasts, thus circumventing embryonic and postnatal gene lethality and avoiding gene deletion in other cell types. Such CtsKCreERT2 mice provide a convenient tool to study in vivo the different facets of osteoclast function in bone physiology during different developmental stages and adulthood of mice.

  12. Exposures to Conditioned Flavours with Different Hedonic Values Induce Contrasted Behavioural and Brain Responses in Pigs

    Science.gov (United States)

    Clouard, Caroline; Jouhanneau, Mélanie; Meunier-Salaün, Marie-Christine; Malbert, Charles-Henri; Val-Laillet, David

    2012-01-01

    This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d.) infusions of 15% glucose (FGlu), lithium chloride (FLiCl), or saline (control treatment, FNaCl). One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three 18FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the FLiCl than the FNaCl or FGlu meals. During the two-choice tests performed one and five weeks later, the FNaCl and FGlu foods were significantly preferred over the FLICl food even in the absence of i.d. infusions. Surprisingly, the FNaCl food was also preferred over the FGlu food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake. PMID:22685528

  13. Exposures to conditioned flavours with different hedonic values induce contrasted behavioural and brain responses in pigs.

    Directory of Open Access Journals (Sweden)

    Caroline Clouard

    Full Text Available This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d. infusions of 15% glucose (F(Glu, lithium chloride (F(LiCl, or saline (control treatment, F(NaCl. One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three (18FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the F(LiCl than the F(NaCl or F(Glu meals. During the two-choice tests performed one and five weeks later, the F(NaCl and F(Glu foods were significantly preferred over the F(LICl food even in the absence of i.d. infusions. Surprisingly, the F(NaCl food was also preferred over the F(Glu food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake.

  14. Exposures to conditioned flavours with different hedonic values induce contrasted behavioural and brain responses in pigs.

    Science.gov (United States)

    Clouard, Caroline; Jouhanneau, Mélanie; Meunier-Salaün, Marie-Christine; Malbert, Charles-Henri; Val-Laillet, David

    2012-01-01

    This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d.) infusions of 15% glucose (F(Glu)), lithium chloride (F(LiCl)), or saline (control treatment, F(NaCl)). One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three (18)FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the F(LiCl) than the F(NaCl) or F(Glu) meals. During the two-choice tests performed one and five weeks later, the F(NaCl) and F(Glu) foods were significantly preferred over the F(LICl) food even in the absence of i.d. infusions. Surprisingly, the F(NaCl) food was also preferred over the F(Glu) food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake.

  15. The role of histamine in estradiol-induced conditioned consumption reductions.

    Science.gov (United States)

    Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

    2005-01-31

    Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

  16. Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization.

    Science.gov (United States)

    Xu, Tao; Johnson, Cole A; Gestwicki, Jason E; Kumar, Anuj

    2010-11-01

    We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. One chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localization signal or nuclear export sequence). The second chimera consists of a target protein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapamycin associated protein 1 (FRAP1, also known as mTor). Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss-of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment.

  17. Human adipose-derived mesenchymal stem cell-conditioned media suppresses inflammatory bone loss in a lipopolysaccharide-induced murine model.

    Science.gov (United States)

    Li, Yu; Gao, Xin; Wang, Jinbing

    2018-02-01

    Conditioned media (CM) from mesenchymal stem cells (MSCs) contains various cytokines, growth factors and microRNAs, which may serve important roles in modulating the inflammatory process. However, the effect of MSC-CM on inflammatory bone loss remains unknown. The present study investigated the effects of conditioned media from human adipose-derived mesenchymal stem cells (AMSC-CM) on the prevention of lipopolysaccharide (LPS)-mediated bone loss in mice. To investigate the underlying mechanisms of this effect, the effects of AMSC-CM on serum levels of inflammation-associated cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and IL-10] in LPS-treated mice, in addition to their mRNA expression in LPS-treated macrophages, was investigated. Micro-computed tomography and histological analysis revealed that AMSC-CM administration effectively inhibited LPS-induced bone destruction in vivo . ELISA analysis indicated that AMSC-CM significantly reduced the serum levels of proinflammatory cytokines (TNF-α, IL-1 and IL-6) in LPS-treated mice. Furthermore, AMSC-CM treatment significantly decreased the mRNA expression levels of TNF-α, IL-1 and IL-6 in macrophages treated with LPS. These findings indicate that AMSC-CM inhibits LPS-induced bone loss by decreasing the production of proinflammatory cytokines, suggesting that the use of AMSC-CM may be a potential therapeutic strategy for the treatment of inflammatory bone loss.

  18. SYVN1, an ERAD E3 Ubiquitin Ligase, Is Involved in GABAAα1 Degradation Associated with Methamphetamine-Induced Conditioned Place Preference

    Directory of Open Access Journals (Sweden)

    Dong-Liang Jiao

    2017-10-01

    Full Text Available Abuse of methamphetamine (METH, a powerful addictive amphetamine-type stimulants (ATS, is becoming a global public health problem. The gamma-aminobutyric acid (GABAergic system plays a critical role in METH use disorders. By using rat METH conditioned place preference (CPP model, we previously demonstrated that METH-associated rewarding memory formation was associated with the reduction of GABAAα1 expression in the dorsal straitum (Dstr, however, the underlying mechanism was unclear. In the present study, we found that METH-induced CPP formation was accompanied by a significant increase in the expression of Synovial apoptosis inhibitor 1 (SYVN1, an endoplasmic reticulum (ER-associated degradation (ERAD E3 ubiquitin ligase, in the Dstr. The siRNA knockdown of SYVN1 significantly increased GABAAα1 protein levels in both primary cultured neurons and rodent Dstr. Inhibition of proteasomal activity by MG132 and Lactacystin significantly increased GABAAα1 protein levels. We further found that SYVN1 knockdown increased GABAAα1 in the intra-ER, but not in the extra-ER. Accordingly, endoplasmic reticulum stress (ERS-associated Glucose-regulated protein 78 (GRP78 and C/EBP homologous protein (CHOP increased. Thus, this study revealed that SYVN1, as the ERAD E3 ubiquitin ligase, was associated with Dstr GABAAα1 degradation induced by METH conditioned pairing.

  19. Phorbol ester tumor promoter induced the synthesis of two major cytoplasmic proteins: identity with two proteins induced under heat-shocked and glucose-starved conditions

    International Nuclear Information System (INIS)

    Zhang, H.; Chen, K.Y.; Liu, A.Y.C.

    1987-01-01

    The regulation of specific protein synthesis by the phorbol ester tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was evaluated using the L-8 and C-2 myoblast and the 3T3-L1 fibroblast cell cultures. TPA increased, by 2-4 fold, the synthesis rates of two cytoplasmic proteins with apparent molecular weights of 89,000 and 74,000 as determined by SDS-polyacrylamide gel electrophoresis and autoradiography. The concentration of TPA and the time of incubation needed to elicit this induction was determined to be 10 μg/ml and 20 hrs, respectively. Increasing the concentration of TPA to 100, 200, and 500 ng/ml did not result in a greater magnitude of induction. The possibility that these two TPA-induced proteins may be identical to proteins with similar molecular weights induced under heat-shocked or glucose-starved conditions was evaluated by 1-D and 2-D gel electrophoresis and autoradiography. Results provided evidence that the TPA-induced 89,000- and 74,000-dalton proteins were identical to hsp 89 and hsp 74, 2 out of a set of 8-9 proteins induced under heat shocked conditions. Furthermore, they are identical to two of the set of glucose-regulated proteins induced under a glucose-starved condition

  20. Radiation-induced secretory protein, clusterin. Its inductive mechanism and biological significance

    International Nuclear Information System (INIS)

    Suzuki, Masatoshi; Boothman, D.A.

    2007-01-01

    This paper describes biochemistry of secretory clusterin (C), its radiation-inductive mechanism and biological significance. C is a glycoprotein found to be secreted from cells given various stresses like radiation and ultraviolet (UV)-ray, and participates to red cell clustering. Human C gene locates on the chromosome 8p21-p12, C has MW of 60 kDa, its precursor undergoes the degrading processing to α- and β-chains to form their heterodimer before glycosylation, and the C is finally secreted. So many other names have been given to C due to its numerous functions which have been discovered in other fields, such as apolipoprotein J. C is abundant in plasma, milk, urine, cerebrospinal fluid, semen, etc. Within 24 hr after X-ray irradiation, extracellular insulin-like growth factor-1 (IGF-1) level is elevated, and through its binding to the receptor, Src/MAPK signaling participates to C expression. Nuclear C, also induced by radiation, is a splicing variant of C and not secreted from cells. C is induced by radiation with as low dose as 2 cGy, which is different from induction of nuclear C. Secreted C is incorporated in cells by endocytosis and promotes the intracellular survival reaction through IGF-1 receptor/MAPK/Egr-1 pathway, whereas nuclear C induces cell apoptosis via unknown mechanism. Further studies are required for elucidation of the roles of secretory and nuclear C in cellular radiation responses. (R.T.)

  1. Context-dependent effects of a single administration of mirtazapine on the expression of methamphetamine-induced conditioned place preference

    Directory of Open Access Journals (Sweden)

    Robin eVoigt

    2012-01-01

    Full Text Available Re-exposure to cues repeatedly associated with methamphetamine (Meth can trigger Meth-seeking and relapse in the abstinent abuser. Weakening the conditioned Meth-associated memory during cue re-exposure may provide a means for relapse-reduction pharmacotherapy. Accordingly, we sought to determine if the atypical antidepressant mirtazapine disrupted the long-term maintenance of Meth-induced conditioned place preference (CPP when administered in conjunction with re-exposure to contextual conditioning cues, and if this effect was altered by Meth being present during cue re-exposure. First, we evaluated the effect of mirtazapine on the maintenance of Meth-induced CPP during re-exposure to either the saline- or Meth-paired chamber 12 days after conditioning. Meth conditioned rats subsequently administered mirtazapine expressed CPP independent of re-exposure to the saline- or Meth-paired chamber; but the magnitude of CPP was significantly less for mirtazapine-treated rats re-exposed to the Meth-paired chamber. Next, we evaluated the effect of mirtazapine on a ‘reinforced re-exposure’ to the Meth-paired context. Administration of mirtazapine vehicle and Meth, prior to re-exposure to the Meth-paired chamber did not disrupt the ability of rats to demonstrate CPP on day 20; however, rats administered mirtazapine and Meth prior to re-exposure to the Meth-paired chamber did not demonstrate CPP. These results indicate a context-dependent effect of mirtazapine, and that the ability of mirtazapine to disrupt the long-term maintenance of CPP is greatest when the atypical antidepressant is tested with a combination of Meth injection and contextual cues.

  2. Computer analysis of the significance of surface boundary conditions on the collection of α-induced charge

    International Nuclear Information System (INIS)

    Terrill, K.W.; Hu, C.; Neureuther, A.R.; California Univ., Berkeley

    1983-01-01

    The collection of α-particle generated charge by collectors surrounded by either uniform reflecting or uniform absorbing surfaces are compared as the two extreme cases of any real condition in IC's. The comparison for varying α-particle energies and collector sizes indicates that the differences in collected charge for the two cases is less than a factor of two if the α-particle strike is through the center of the collector. It is shown that variation of collected charge with feature length is approximately linear in both cases. The effect of scaling on soft errors in static RAM's is discussed. It is assumed that the charge transport is by diffusion only. (author)

  3. Identification of warm day and cool night conditions induced flowering-related genes in a Phalaenopsis orchid hybrid by suppression subtractive hybridization.

    Science.gov (United States)

    Li, D M; Lü, F B; Zhu, G F; Sun, Y B; Xu, Y C; Jiang, M D; Liu, J W; Wang, Z

    2014-02-14

    The influence of warm day and cool night conditions on induction of spikes in Phalaenopsis orchids has been studied with respect to photosynthetic efficiency, metabolic cycles and physiology. However, molecular events involved in spike emergence induced by warm day and cool night conditions are not clearly understood. We examined gene expression induced by warm day and cool night conditions in the Phalaenopsis hybrid Fortune Saltzman through suppression subtractive hybridization, which allowed identification of flowering-related genes in warm day and cool night conditions in spikes and leaves at vegetative phase grown under warm daily temperatures. In total, 450 presumably regulated expressed sequence tags (ESTs) were identified and classified into functional categories, including metabolism, development, transcription factor, signal transduction, transportation, cell defense, and stress. Furthermore, database comparisons revealed a notable number of Phalaenopsis hybrid Fortune Saltzman ESTs that matched genes with unknown function. The expression profiles of 24 genes (from different functional categories) have been confirmed by quantitative real-time PCR in induced spikes and juvenile apical leaves. The results of the real-time PCR showed that, compared to the vegetative apical leaves, the transcripts of genes encoding flowering locus T, AP1, AP2, KNOX1, knotted1-like homeobox protein, R2R3-like MYB, adenosine kinase 2, S-adenosylmethionine synthetase, dihydroflavonol 4-reductase, and naringenin 3-dioxygenase accumulated significantly higher levels, and genes encoding FCA, retrotransposon protein Ty3 and C3HC4-type RING finger protein accumulated remarkably lower levels in spikes of early developmental stages. These results suggested that the genes of two expression changing trends may play positive and negative roles in the early floral transition of Phalaenopsis orchids. In conclusion, spikes induced by warm day and cool night conditions were complex in

  4. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

  5. Effect of storage conditions on graft of polypropylene non-woven fabric induced by electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Young; Jeun, Joon Pyo; Kang, Phil Hyun [Radiation Research Dvision for Industry and Environment, Korea Atomic Energy Research Institute, Jeongeup(Korea, Republic of)

    2015-05-15

    In this study, we fabricated effect of storage conditions on graft of polypropylene (PP) non-woven fabric induced by electron beam. The electron beam irradiations on PP non-woven fabric were carried out over a range of irradiation doses from 25 to 100 kGy to make free radicals on fabric surface. The radical measurement was established by electron spin resonance (ESR) for confirming the changes of the alkyl radical and peroxy radical according to effect of storage time, storage temperature and atmosphere. It was observed that the free radicals were increased with irradiation dose and decreased with storage time due to the continuous oxidation. However, the radical extinction was significantly delayed due to reduced mobility of radicals at extremely low temperature. The degree of graft based on the analysis of ESR was investigated. The conditions of graft reaction were set at a temperature: 60 degrees Celcius, reaction time: 6 hours and styrene monomer concentration: 20 wt%.

  6. The effects of implant topography on osseointegration under estrogen deficiency induced osteoporotic conditions: Histomorphometric, transcriptional and ultrastructural analysis.

    Science.gov (United States)

    Du, Zhibin; Xiao, Yin; Hashimi, Saeed; Hamlet, Stephen M; Ivanovski, Saso

    2016-09-15

    Compromised bone quality and/or healing in osteoporosis are recognised risk factors for impaired dental implant osseointegration. This study examined the effects of (1) experimentally induced osteoporosis on titanium implant osseointegration and (2) the effect of modified implant surface topography on osseointegration under osteoporosis-like conditions. Machined and micro-roughened surface implants were placed into the maxillary first molar root socket of 64 ovariectomised and sham-operated Sprague-Dawley rats. Subsequent histological and SEM observations showed tissue maturation on the micro-rough surfaced implants in ovariectomised animals as early as 3days post-implantation. The degree of osseointegration was also significantly higher around the micro-rough implants in ovariectomised animals after 14days of healing although by day 28, similar levels of osseointegration were found for all test groups. The micro-rough implants significantly increased the early (day 3) gene expression of alkaline phosphatase, osteocalcin, receptor activator of nuclear factor kappa-B ligand and dentin matrix protein 1 in implant adherent cells. By day 7, the expression of inflammatory genes decreased while the expression of the osteogenic markers increased further although there were few statistically significant differences between the micro-rough and machined surfaces. Osteocyte morphology was also affected by estrogen deficiency with the size of the cells being reduced in trabecular bone. In conclusion, estrogen deficiency induced osteoporotic conditions negatively influenced the early osseointegration of machined implants while micro-rough implants compensated for these deleterious effects by enhancing osteogenic cell differentiation on the implant surface. Lower bone density, poor bone quality and osseous microstructural changes are all features characteristic of osteoporosis that may impair the osseointegration of dental implants. Using a clinically relevant trabecular bone

  7. Involvement of brain catalase activity in the acquisition of ethanol-induced conditioned place preference.

    Science.gov (United States)

    Font, Laura; Miquel, Marta; Aragon, Carlos M G

    2008-03-18

    It has been suggested that some of the behavioral effects produced by ethanol are mediated by its first metabolite, acetaldehyde. The present research addressed the hypothesis that catalase-dependent metabolism of ethanol to acetaldehyde in the brain is an important step in the production of ethanol-related affective properties. Firstly, we investigated the contribution of brain catalase in the acquisition of ethanol-induced conditioned place preference (CPP). Secondly, the specificity of the catalase inhibitor 3-amino-1,2,4-triazole (AT) was evaluated with morphine- and cocaine-induced CPP. Finally, to investigate the role of catalase in the process of relapse to ethanol seeking caused by re-exposure to ethanol, after an initial conditioning and extinction, mice were primed with saline and ethanol or AT and ethanol and tested for reinstatement of CPP. Conditioned place preference was blocked in animals treated with AT and ethanol. Morphine and cocaine CPP were unaffected by AT treatment. However, the reinstatement of place preference was not modified by catalase inhibition. Taken together, the results of the present study indicate that the brain catalase-H(2)O(2) system contributes to the acquisition of affective-dependent learning induced by ethanol, and support the involvement of centrally-formed acetaldehyde in the formation of positive affective memories produced by ethanol.

  8. Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

    Science.gov (United States)

    Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

    2012-01-01

    Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

  9. Significance and nature of bystander responses induced by various agents.

    Science.gov (United States)

    Verma, Neha; Tiku, Ashu Bhan

    2017-07-01

    Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Clinical significance of determination of the changes of plasma vasoactive substances ET, NO, CGRP levels in patients with pregnancy induced hypertension

    International Nuclear Information System (INIS)

    Zhang Danhui

    2006-01-01

    Objective: To investigate the clinical significance of changes of plasma ET, CGRP and NO levels in patients with pregnancy induced hypertension. Methods: Plasma levels of ET, CGRP (with RIA) and NO (with colorimetry) were measured in 36 patients with pregnancy induced hypertension 30 women with normal pregnancy and 32 controls. Results: Plasma levels of ET, CGRP and NO in normal pregnant women were not significantly different from those in controls (P>0.05) and plasma levels of ET, CGRP and NO in patients with mild pregnancy induced hypertension (n=12) were not significantly different flora those in normal pregnant women (P>0.05), However, plasma levels of ET in patients with moderate (n=14) and severe (n=10) pregnancy induced hypertension were significantly higher than those in normal pregant women, while levels of CGRP and NO were significantly lower (all P< 0.01). Conclusion: Detection of changes of plasma ET, CGRP and NO contents in patients with pregnancy induced hypertension provides a valuable laboratory basis for study of relationship between endothelial cell function and pathogenesis of hypertension. (authors)

  11. Risk-Significant Adverse Condition Awareness Strengthens Assurance of Fault Management Systems

    Science.gov (United States)

    Fitz, Rhonda

    2017-01-01

    As spaceflight systems increase in complexity, Fault Management (FM) systems are ranked high in risk-based assessment of software criticality, emphasizing the importance of establishing highly competent domain expertise to provide assurance. Adverse conditions (ACs) and specific vulnerabilities encountered by safety- and mission-critical software systems have been identified through efforts to reduce the risk posture of software-intensive NASA missions. Acknowledgement of potential off-nominal conditions and analysis to determine software system resiliency are important aspects of hazard analysis and FM. A key component of assuring FM is an assessment of how well software addresses susceptibility to failure through consideration of ACs. Focus on significant risk predicted through experienced analysis conducted at the NASA Independent Verification Validation (IVV) Program enables the scoping of effective assurance strategies with regard to overall asset protection of complex spaceflight as well as ground systems. Research efforts sponsored by NASA's Office of Safety and Mission Assurance defined terminology, categorized data fields, and designed a baseline repository that centralizes and compiles a comprehensive listing of ACs and correlated data relevant across many NASA missions. This prototype tool helps projects improve analysis by tracking ACs and allowing queries based on project, mission type, domaincomponent, causal fault, and other key characteristics. Vulnerability in off-nominal situations, architectural design weaknesses, and unexpected or undesirable system behaviors in reaction to faults are curtailed with the awareness of ACs and risk-significant scenarios modeled for analysts through this database. Integration within the Enterprise Architecture at NASA IVV enables interfacing with other tools and datasets, technical support, and accessibility across the Agency. This paper discusses the development of an improved workflow process utilizing this

  12. Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

    DEFF Research Database (Denmark)

    Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

    2018-01-01

    Hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions...... and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...

  13. Natural and induced endoreic hydrological conditions in the Alta Murgia karstic region (Apulia, Southern Italy)

    Science.gov (United States)

    Canora, F.; Fidelibus, M. D.; Spilotro, G.

    2009-04-01

    mechanized agriculture. While the original situation of Alta Murgia recharge area was able to assure the best conditions for high infiltration rate, not only for the positive role of the drystone walls in holding the soil and slowing down the runoff, but also for the morphological characteristics of the karstic surface textures, stone shattering, by flattening and deeply modifying large part of the original karstic textures and landscape and by demolishing drystone walls, produced severe alteration of the hydrological behaviour of surface and epikarstic textures, increase of runoff and erosion, and substantial geomorphological variations. The land use change thus caused a significant damage to the fragile karstic environment, increasing its vulnerability, and clearly modifying the hydrogeological balance. To assess the impact of endoreic (natural and induced) conditions on the water balance and the significance of the karstic textures modifications, field and laboratory surveys have been carried out for defining at field scale the hydraulic and physical characteristics of the epikarstic textures and their influence respect to the flowing runoff threshold. Such a characterization was mainly aimed at assessing their infiltration capacity. Moreover, detailed geomorphological surveys, in situ investigations, and aerial photo analysis were used to verify the role of the endoreic (natural and induced) conditions, in order to define their control on hydrogeological processes. Simulations of the water balance carried out in a selected part of the recharge area subject to land use change, which originally included natural surface textures and drystone walls. The comparison between the infiltration rate in the natural conditions (by considering the role of natural endoreic basins and a variable retaining capability of induced endoreic conditions created by drystone walls) and that one calculated for the present situation (stone shattered soil with geomorphological variations due to

  14. Metabotropic glutamate receptor I (mGluR1) antagonism impairs cocaine-induced conditioned place preference via inhibition of protein synthesis.

    Science.gov (United States)

    Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-Qing; Liu, Qing-Song

    2013-06-01

    Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abuse. We report that group I mGluR agonist DHPG induced more pronounced initial depression of inhibitory postsynaptic currents (IPSCs) followed by modest long-term depression (I-LTD) in dopamine neurons of rat ventral tegmental area (VTA) through the activation of mGluR1. The early component of DHPG-induced depression of IPSCs was mediated by the cannabinoid CB1 receptors, while DHPG-induced I-LTD was dependent on protein synthesis. Western blotting analysis indicates that mGluR1 was coupled to extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways to increase translation. We also show that cocaine conditioning activated translation machinery in the VTA via an mGluR1-dependent mechanism. Furthermore, intra-VTA microinjections of mGluR1 antagonist JNJ16259685 and protein synthesis inhibitor cycloheximide significantly attenuated or blocked the acquisition of cocaine-induced conditioned place preference (CPP) and activation of translation elongation factors. Taken together, these results suggest that mGluR1 antagonism inhibits de novo protein synthesis; this effect may block the formation of cocaine-cue associations and thus provide a mechanism for the reduction in CPP to cocaine.

  15. Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.

    Science.gov (United States)

    Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

    2013-05-01

    Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Unfolded protein response is required for Aspergillus oryzae growth under conditions inducing secretory hydrolytic enzyme production.

    Science.gov (United States)

    Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

    2015-12-01

    Unfolded protein response (UPR) is an intracellular signaling pathway for adaptation to endoplasmic reticulum (ER) stress. In yeast UPR, Ire1 cleaves the unconventional intron of HAC1 mRNA, and the functional Hac1 protein translated from the spliced HAC1 mRNA induces the expression of ER chaperone genes and ER-associated degradation genes for the refolding or degradation of unfolded proteins. In this study, we constructed an ireA (IRE1 ortholog) conditionally expressing strain of Aspergillus oryzae, a filamentous fungus producing a large amount of amylolytic enzymes, and examined the contribution of UPR to ER stress adaptation under physiological conditions. Repression of ireA completely blocked A. oryzae growth under conditions inducing the production of hydrolytic enzymes, such as amylases and proteases. This growth defect was restored by the introduction of unconventional intronless hacA (hacA-i). Furthermore, UPR was observed to be induced by amylolytic gene expression, and the disruption of the transcriptional activator for amylolytic genes resulted in partial growth restoration of the ireA-repressing strain. In addition, a homokaryotic ireA disruption mutant was successfully generated using the strain harboring hacA-i as a parental host. These results indicated that UPR is required for A. oryzae growth to alleviate ER stress induced by excessive production of hydrolytic enzymes. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Analysis of flow induced valve operation and pressure wave propagation for single and two-phase flow conditions

    International Nuclear Information System (INIS)

    Nagel, H.

    1986-01-01

    The flow induced valve operation is calculated for single and two-phase flow conditions by the fluid dynamic computer code DYVRO and results are compared to experimental data. The analysis show that the operational behaviour of the valves is not only dependent on the condition of the induced flow, but also the pipe flow can cause a feedback as a result of the induced pressure waves. For the calculation of pressure wave propagation in pipes of which the operation of flow induced valves has a considerable influence it is therefore necessary to have a coupled analysis of the pressure wave propagation and the operational behaviour of the valves. The analyses of the fast transient transfer from steam to two-phase flow show a good agreement with experimental data. Hence even these very high loads on pipes resulting from such fluid dynamic transients can be calculated realistically. (orig.)

  18. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    Science.gov (United States)

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  19. Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Oyinbo Charles A.

    2016-12-01

    Full Text Available Background: Alcohol-induced cerebellar neurodegeneration is a neuroadaptation that is associated with chronic alcohol abuse. Conventional drugs have been largely unsatisfactory in preventing neurodegeneration. Yet, multimodal neuro-protective therapeutic agents have been hypothesised to have high therapeutic potential for the treatment of CNS conditions; there is yet a dilemma of how this would be achieved. Contrarily, medicinal botanicals are naturally multimodal in their mechanism of action.

  20. Conditioned taste avoidance induced by forced and voluntary wheel running in rats.

    Science.gov (United States)

    Forristall, J R; Hookey, B L; Grant, V L

    2007-03-01

    Voluntary exercise by rats running in a freely rotating wheel (free wheel) produces conditioned taste avoidance (CTA) of a flavored solution consumed before running [e.g., Lett, B.T., Grant, V.L., 1996. Wheel running induces conditioned taste aversion in rats trained while hungry and thirsty. Physiol. Behav. 59, 699-702]. Forced exercise, swimming or running, also produces CTA in rats [e.g., Masaki, T., Nakajima, S., 2006. Taste aversion induced by forced swimming, voluntary running, forced running, and lithium chloride injection treatments. Physiol. Behav. 88, 411-416]. Energy expenditure may be the critical factor in producing such CTA. If so, forced running in a motorized running wheel should produce CTA equivalent to that produced by a similar amount of voluntary running. In two experiments, we compared forced running in a motorized wheel with voluntary running in a free wheel. Mean distance run over 30 min was equated as closely as possible in the two apparatuses. Both types of exercise produced CTA relative to sedentary, locked-wheel controls. However, voluntary running produced greater CTA than forced running. We consider differences between running in the free and motorized wheels that may account for the differences in strength of CTA.

  1. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Directory of Open Access Journals (Sweden)

    Ida M Smith

    Full Text Available Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  2. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Science.gov (United States)

    Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

    2016-01-01

    Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC) function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  3. Adolescent social defeat induced alterations in anxious behavior and cognitive flexibility in adult mice: effects of developmental stage and social condition

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    2016-07-01

    Full Text Available Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using resident-intruder stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, PND 28-37, late adolescence (LA, PND 38-47, and adulthood (ADULT, PND 70-79 and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST, were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting in adulthood but not during adolescence. In experiment 2, we further examined the effects of social condition (isolation or social housing after stress on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive function are differentially

  4. The problem of induced genomic instability in the child organism under conditions of long-term effect of small radiation doses

    International Nuclear Information System (INIS)

    Suskov, I.I.; Kuz'mina, N.S.

    2001-01-01

    The phenomenological aspects of the genomic instability induced in the descendants of the multi-divided cells having been exposed to the radiation are examined. It is demonstrated that the regularity of the genomic instability induction do not correspond to the classical conception of the radiation genetics (hit principle and target theory). The mechanisms and the biological significance of this new genetic phenomenon in the child organism under conditions of low-intensive effect of small-dose radiation and its connection with the state of health are discussed [ru

  5. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

    Science.gov (United States)

    Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2014-11-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

  6. Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

    Science.gov (United States)

    Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

    2014-07-15

    The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Blocking of conditioned taste avoidance induced by wheel running.

    Science.gov (United States)

    Pierce, W David; Heth, C Donald

    2010-01-01

    In Experiment 1, compared to non-reinforced presentation of a food stimulus (A-->no US), the association of a food stimulus with wheel running (A-->US) blocked subsequent avoidance of a distinctive flavor (X), when both the food and flavor were followed by wheel running (AX-->US). Experiment 2 replicated and extended the blocking effect, demonstrating that the amount of avoidance of X after AX-->wheel training depended on the correlation between A-alone trials and wheel running-the predictiveness of the A stimulus. The present study is the first to demonstrate associative blocking of conditioned taste avoidance (CTA) induced by wheel running and strongly implicates associative learning as the basis for this kind of avoidance. 2009 Elsevier B.V. All rights reserved.

  8. Inflammatory conditions induce IRES-dependent translation of cyp24a1.

    Directory of Open Access Journals (Sweden)

    Daniela Rübsamen

    Full Text Available Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR-kinase, alternative modes of translation, such as internal ribosome entry site (IRES-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM. Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.

  9. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells

    International Nuclear Information System (INIS)

    Chen Yixing; Zeng Zhaochong; Sun Jing; Huang Yan; Zhang Zhenyu; Zeng Haiying

    2015-01-01

    Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow–derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague–Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury. (author)

  10. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chuan-Ho, E-mail: chtang@nmmba.gov.tw [Institute of Marine Biodiversity and Evolutionary Biology, National Dong Hwa University, Pingtung, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Lin, Ching-Yu [Institute of Environmental Health, National Taiwan University, Taipei City, Taiwan, ROC (China); Lee, Shu-Hui [Center of General Education, National Kaohsiung Marine University, Kaohsiung, Taiwan, ROC (China); Wang, Wei-Hsien [National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Department of Marine Biotechnology and Resources and Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC (China)

    2014-03-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  11. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    International Nuclear Information System (INIS)

    Tang, Chuan-Ho; Lin, Ching-Yu; Lee, Shu-Hui; Wang, Wei-Hsien

    2014-01-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  12. X-ray radiation induced bystander effects of human glioblastoma T98G cells under hypoxia condition

    International Nuclear Information System (INIS)

    Zhang Jianghong; Jin Yizun; Shao Chunlin; Prise, K.M.

    2008-01-01

    Non-irradiated bystander human glioblastoma T98G cells were co-cultured (CC) with irradiated cells or treated with conditioned medium (CM) from irradiated cells under hypoxic condition, then micronucleus (MN) of both irradiated cells and bystander cells were measured for the investigation of radiation induced bystander effect and its mechanism. It has been found that the MN yield (Y MN ) of non-irradiated bystander T98G cells is obviously enhanced after the cell co-culture, or CM treatment, but this increment is diminished by free radical scavenger, dimethyl sulfoxide (DMSO). When hypoxic or normoxic T98G cells are treated with CM obtained from irradiated cells under either hypoxic or normoxic condition, the biggest bystander response has been observed in the group of hypoxic by- stander cells treated with CM from irradiated normoxic cells. However, all of these increments of bystander Y MN could be eliminated by aminoguanidine, an iNOS inhibitor. Therefore, under hypoxic condition, free radicals, especially reactive oxygen species and nitric oxide, are involved in the bystander response induced by irradiated T98G cells. (authors)

  13. Influences of buoyancy and thermal boundary conditions on heat transfer with naturally-induced flow

    International Nuclear Information System (INIS)

    Jackson, J.D.; Li, J.

    2002-01-01

    A fundamental study is reported of heat transfer from a vertical heated tube to air which is induced naturally upwards through it by the action of buoyancy. Measurements of local heat transfer coefficient were made using a specially designed computer-controlled power supply and measurement system for conditions of uniform wall temperature and uniform wall heat flux. The effectiveness of heat transfer proved to be much lower than for conditions of forced convection. It was found that the results could be correlated satisfactorily when presented in terms of dimensionless parameters similar to those used for free convection heat transfer from vertical surfaces provided that the heat transfer coefficients were evaluated using local fluid bulk temperature calculated utilising the measured values of flow rate induced through the system. Additional experiments were performed' with pumped flow. These covered the entire mixed convection region. It was found that the data for naturally-induced flow mapped onto the pumped flow data when presented in terms of Nusselt number ratio (mixed to forced) and buoyancy parameter. Computational simulations of the experiments were performed using an advanced computer code which incorporated a buoyancy-influenced, variable property, developing wall shear flow formulation and a low Reynolds number k-ε turbulence model. These reproduced observed behaviour quite well. (author)

  14. Identifying conditions for inducible protein production in E. coli: combining a fed-batch and multiple induction approach

    Directory of Open Access Journals (Sweden)

    Choi Young J

    2006-08-01

    Full Text Available Abstract Background In the interest of generating large amounts of recombinant protein, inducible systems have been studied to maximize both the growth of the culture and the production of foreign proteins. Even though thermo-inducible systems were developed in the late 1970's, the number of studies that focus on strategies for the implementation at bioreactor scale is limited. In this work, the bacteriophage lambda PL promoter is once again investigated as an inducible element but for the production of green fluorescent protein (GFP. Culture temperature, induction point, induction duration and number of inductions were considered as factors to maximize GFP production in a 20-L bioreactor. Results It was found that cultures carried out at 37°C resulted in a growth-associated production of GFP without the need of an induction at 42°C. Specific production was similar to what was achieved when separating the growth and production phases. Shake flask cultures were used to screen for desirable operating conditions. It was found that multiple inductions increased the production of GFP. Induction decreased the growth rate and substrate yield coefficients; therefore, two time domains (before and after induction having different kinetic parameters were created to fit a model to the data collected. Conclusion Based on two batch runs and the simulation of culture dynamics, a pre-defined feeding and induction strategy was developed to increase the volumetric yield of a temperature regulated expression system and was successfully implemented in a 20-L bioreactor. An overall cell density of 5.95 g DW l-1 was achieved without detriment to the cell specific production of GFP; however, the production of GFP was underestimated in the simulations due to a significant contribution of non-growth associated product formation under limiting nutrient conditions.

  15. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

    DEFF Research Database (Denmark)

    Vægter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas

    2014-01-01

    Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesised that the spatial and temporal manifestations of EIH and CPM were comparable. Eighty healthy subjects (40 females), between 18......-65 years participated in this randomized repeated-measures crossover trial with data collection on two different days. CPM was assessed by two different cold pressor tests (hand,foot). EIH was assessed through two intensities of aerobic bicycling exercises and two intensities of isometric muscle...... tests and after all of the exercise conditions, except low intensity bicycling. EIH after bicycling was increased in women compared to men. CPM and the EIH response after isometric exercises were comparable in men and women and not affected by age. The EIH response was larger in the exercising body part...

  16. Naloxone attenuates the conditioned place preference induced by wheel running in rats.

    Science.gov (United States)

    Lett, B T; Grant, V L; Koh, M T

    2001-02-01

    Pairings, during which an episode of wheel running is followed by confinement in a distinctive place, produce conditioned place preference (CPP) in rats. This finding indicates that wheel running has a rewarding effect that outlasts the activity itself. In two similar experiments, we tested the hypothesis that this rewarding effect of wheel running is mediated by endogenous opioids. During a paired trial, the rats in the naloxone group were first allowed to wheel run for 2 h, then injected with naloxone (0.5 or 0.1 mg/kg in Experiments 1 and 2, respectively), and 10 min later placed in a distinctive chamber. During an unpaired trial, these rats were confined in an adjoining chamber without wheel running. Naloxone was injected before placement in both chambers, so that if naloxone-induced conditioned place aversion occurred, it would have counteracting effects on performance during the preference test. The rats in the saline group were similarly treated, except that saline was injected instead of naloxone. CPP occurred in the saline group, but not in the naloxone group. Thus, naloxone attenuated the CPP induced by wheel running. This finding supports the hypothesis that the rewarding effect of wheel running is mediated by endogenous opioids.

  17. Effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain induced by CFA adjuvant

    Directory of Open Access Journals (Sweden)

    Vida Nazemian

    2016-07-01

    Full Text Available Background: Rheumatoid arthritis is a type of inflammatory pain and is an autoimmune and chronic inflammatory disease which can lead to hyperalgesia, edema and decreased motor activity in affected area. Mesenchymal stem cells conditioned medium (MSC-CM has anti-inflammatory mediators which can regulate the immune responses, alleviate inflammatory symptoms and has a paracrine effects too. The aim of this study was to evaluate the effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain which induced by CFA adjuvant.Materials and Methods: Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by single subcutaneous injection of CFA into the rats hind paw on day zero. MSC-CM was administered daily and intraperitoneal during the 21 days of the study after CFA injection. Hyperalgesia and edema were assessed on days 0, 7, 14 and 21 of the study respectively with radian heat and plethysmometer instrument.Results: The results of this study indicated the significant roles of MSC-CM in betterment of inflammatory symptoms such as hyperalgesia and edema during different stages of inflammation caused by CFA. The continuing injection of MSC-CM could reduce the inflammatory symptoms.Conclusion: Long term treatment by MSC-CM can alleviate hyperalgesia and edema and decrease those to the level of the time before induction of inflammation.   

  18. Clinical significance of stress-induced ST segment changes in patients with previous myocardial infarction

    International Nuclear Information System (INIS)

    Futagami, Yasuo; Hamada, Masayuki; Makino, Katsutoshi; Ichikawa, Takehiko; Konishi, Tokuji

    1984-01-01

    To explain the clinical significance of stress(st)-induced ST-segment (ST) changes postinfarction, 93 patients with previous myocardial infarction (MI) were performed st- 201 Tl myocardial single photon emission computed tomography (SPECT) and compared ST changes with SPECT, coronary arteriographic and left ventriculographic findings. 30 out of 93 cases (32%) had ST depression, 20 (21.5%) had ST elevation, 9 (10%) had both ST depression and elevation and remaining 34 (36.5 %) had no significant ST changes. In single vessel disease, ST depression were noted in 29% (12/42), while in multivessel disease, 53% (27/51). 35 out of 39 cases (90%) with ST depression had transient perfusion defect but no apparent relation was noted between location of ST depression on ECG and region of transient perfusion defect in SPECT. All of 28 cases with ST elevation were noted in anterior MI cases, and 26 out of these showed severe LV wall motion abnormality in contrast left ventriculography and broad anterior permanent defect in SPECT. Only 15 cases (54%) showed slight redistribution. Thus, we conclude that in patients with previous MI, st-induced ST depression seems to reflect myocardial ischemia and ST elevation possibly related abnormal LV wall motion. (author)

  19. Vortex-Induced Vibrations of a Square Cylinder with Damped Free-End Conditions

    Directory of Open Access Journals (Sweden)

    S. Manzoor

    2013-01-01

    Full Text Available The authors report the results of vortex-induced vibrations of a square cylinder in a wind tunnel. This constitutes a high mass ratio environment. The square cylinder is mounted in the wind tunnel in such a fashion that it only performs rigid body oscillations perpendicular to the flow direction with damped free-end conditions. This physical situation allows a direct evaluation for analytical models relying on simplified 2D assumptions. The results are also compared with two-dimensional fluid-structure (CFD-CSD numerical simulations. The comparison shows that despite having one-dimensional motion, the analytical model does not predict the VIV region with correctness. Results show that the numerical simulations and experimental results differ from the analytical model for the prediction of reduced velocity corresponding to peak amplitude. Also the analytical reduced velocity envelope is underpredicted compared to both numerical simulations and experimental data despite the structure being lightly damped. The findings are significant as the experimental results for freely oscillating high mass ratio body show differences from the low mass ratio especially in the transition between VIV and galloping regions. However the numerical simulations show comparatively close agreement.

  20. Light scattering under conditions of nonstationary electromagnetically induced transparency

    International Nuclear Information System (INIS)

    Larionov, N V; Sokolov, I M

    2007-01-01

    The propagation of probe radiation pulses in ultracold atomic ensembles is studied theoretically under conditions of electromagnetically induced transparency. The pulse 'stopping' process is considered which takes place upon nonadiabatic switching off and subsequent switching on the control field. We analysed the formation of an inverted recovered probe radiation pulse, i.e. the pulse propagating in the direction opposite to the propagation direction before the pulse stopping. Based on this analysis, a scheme is proposed for lidar probing atomic or molecular clouds in which the probe pulse penetrates into a cloud over the specified depth, while information on the cloud state is obtained from the parameters of the inverted pulse. Calculations are performed for an ensemble of 87 Rb atoms. (fifth seminar in memory of d.n. klyshko)

  1. Role of transglutaminase 2 in A1 adenosine receptor- and β2-adrenoceptor-mediated pharmacological pre- and post-conditioning against hypoxia-reoxygenation-induced cell death in H9c2 cells.

    Science.gov (United States)

    Vyas, Falguni S; Nelson, Carl P; Dickenson, John M

    2018-01-15

    Pharmacologically-induced pre- and post-conditioning represent attractive therapeutic strategies to reduce ischaemia/reperfusion injury during cardiac surgery and following myocardial infarction. We have previously reported that transglutaminase 2 (TG2) activity is modulated by the A 1 adenosine receptor and β 2 -adrenoceptor in H9c2 cardiomyoblasts. The primary aim of this study was to determine the role of TG2 in A 1 adenosine receptor and β 2 -adrenoceptor-induced pharmacological pre- and post-conditioning in the H9c2 cells. H9c2 cells were exposed to 8h hypoxia (1% O 2 ) followed by 18h reoxygenation, after which cell viability was assessed by monitoring mitochondrial reduction of MTT, lactate dehydrogenase release and caspase-3 activation. N 6 -cyclopentyladenosine (CPA; A 1 adenosine receptor agonist), formoterol (β 2 -adrenoceptor agonist) or isoprenaline (non-selective β-adrenoceptor agonist) were added before hypoxia/reoxygenation (pre-conditioning) or at the start of reoxygenation following hypoxia (post-conditioning). Pharmacological pre- and post-conditioning with CPA and isoprenaline significantly reduced hypoxia/reoxygenation-induced cell death. In contrast, formoterol did not elicit protection. Pre-treatment with pertussis toxin (G i/o -protein inhibitor), DPCPX (A 1 adenosine receptor antagonist) or TG2 inhibitors (Z-DON and R283) attenuated the A 1 adenosine receptor-induced pharmacological pre- and post-conditioning. Similarly, pertussis toxin, ICI 118,551 (β 2 -adrenoceptor antagonist) or TG2 inhibition attenuated the isoprenaline-induced cell survival. Knockdown of TG2 using small interfering RNA (siRNA) attenuated CPA and isoprenaline-induced pharmacological pre- and post-conditioning. Finally, proteomic analysis following isoprenaline treatment identified known (e.g. protein S100-A6) and novel (e.g. adenine phosphoribosyltransferase) protein substrates for TG2. These results have shown that A 1 adenosine receptor and β 2 -adrenoceptor-induced

  2. Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

    Science.gov (United States)

    1992-01-01

    SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets

  3. Failure to Find Ethanol-Induced Conditioned Taste Aversion in Honey Bees (Apis mellifera L.).

    Science.gov (United States)

    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.

  4. Ethanol-induced conditioned taste avoidance: reward or aversion?

    Science.gov (United States)

    Liu, Chuang; Showalter, John; Grigson, Patricia Sue

    2009-03-01

    Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both

  5. NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.

    Science.gov (United States)

    Sikora, Magdalena; Tokarski, Krzysztof; Bobula, Bartosz; Zajdel, Joanna; Jastrzębska, Kamila; Cieślak, Przemysław Eligiusz; Zygmunt, Magdalena; Sowa, Joanna; Smutek, Magdalena; Kamińska, Katarzyna; Gołembiowska, Krystyna; Engblom, David; Hess, Grzegorz; Przewlocki, Ryszard; Rodriguez Parkitna, Jan

    2016-01-01

    Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.

  6. Physical Condition Does Not Affect Gravity-Induced Loss of Consciousness during Human Centrifuge Training in Well-Experienced Young Aviators.

    Directory of Open Access Journals (Sweden)

    Jinhee Park

    Full Text Available Consensus on whether physical condition affects the risk of gravity-induced loss of consciousness (G-LOC has not been reached, and most previous studies about the issue did not include well-experienced aviators. We compared the physical conditions of well-experienced young aviators according to the occurrence of G-LOC during human centrifuge training.Among 361 young male aviators on active flight duty with experience in high performance aircrafts for at least 2 years, 350 had full data available and were reviewed in this study. We divided the aviators into the G-LOC group and the non-G-LOC group according to their human centrifuge training results. We then compared their basic characteristics, body composition, physical fitness level, and pulmonary function.Twenty nine aviators (8.3% who experienced G-LOC during human centrifuge training in their first trials were classified into the G-LOC group. There was no difference in physical condition of aviators between the two groups.Young aviators with experience in G-LOC showed no difference in physical condition such as muscle mass, strength, and general endurance from the aviators with no such experience. Although more studies are needed, physical condition does not seem to be a significant determinant of G-LOC among the experienced aviators.

  7. Physical Condition Does Not Affect Gravity-Induced Loss of Consciousness during Human Centrifuge Training in Well-Experienced Young Aviators.

    Science.gov (United States)

    Park, Jinhee; Yun, Chul; Kang, Seungcheol

    2016-01-01

    Consensus on whether physical condition affects the risk of gravity-induced loss of consciousness (G-LOC) has not been reached, and most previous studies about the issue did not include well-experienced aviators. We compared the physical conditions of well-experienced young aviators according to the occurrence of G-LOC during human centrifuge training. Among 361 young male aviators on active flight duty with experience in high performance aircrafts for at least 2 years, 350 had full data available and were reviewed in this study. We divided the aviators into the G-LOC group and the non-G-LOC group according to their human centrifuge training results. We then compared their basic characteristics, body composition, physical fitness level, and pulmonary function. Twenty nine aviators (8.3%) who experienced G-LOC during human centrifuge training in their first trials were classified into the G-LOC group. There was no difference in physical condition of aviators between the two groups. Young aviators with experience in G-LOC showed no difference in physical condition such as muscle mass, strength, and general endurance from the aviators with no such experience. Although more studies are needed, physical condition does not seem to be a significant determinant of G-LOC among the experienced aviators.

  8. Modulation of Itch by Conditioning Itch and Pain Stimulation in Healthy Humans.

    Science.gov (United States)

    Andersen, Hjalte H; van Laarhoven, Antoinette I M; Elberling, Jesper; Arendt-Nielsen, Lars

    2017-12-01

    Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  9. Fibroblast and T cells conditioned media induce maturation dendritic cell and promote T helper immune response

    Directory of Open Access Journals (Sweden)

    Masoumeh Asadi

    2012-06-01

    Full Text Available Dendritic cells (DCs induce pathogen-specific T cell responses. We comprehensively studied the effects of addition of maturation stimulus, fibroblasts (fibroblast conditioned medium, PHA activated T cells (T cell conditioned medium, and mixture of fibroblast & PHA activated T cells (FCM-TCCM conditioned media on maturation of DCs. Monocytes were cultured with GM-CSF and IL-4 for five days. Maturation factors included MCM and TNF-α as control group. FCM and TCCM, or FCM-TCCM supernatant were considered as the treatment group. Tumor antigens were added at day five. Matured DCs were harvested at day seven. Phenotypic and functional analyses were carried out using anti (CD14, CD80, CD86, CD83 and HLA-DR monoclonal antibodies. Phagocytic activity, mixed lymphocyte reaction (MLR and cytokine production were also evaluated. At the end of culturing period, significantly fully matured DCs with large amount cytoplasm and copious dendritic projections were found in the presence of MCM, TNF-α with or without FCM, TCCM, FCM as well as TCCM. Flow cytometric analysis revealed that expression of CD14 decreased in particular in treated DCs, at the 5th day and expression of CD80, CD86 and HLA-DR was higher when FCM, TCCM, FCM plus TCCM were added to maturation factor. This study demonstrated that DCs matured with these methods had optimum function in comparison with either factor alone.

  10. Swimming-induced pulmonary oedema an uncommon condition diagnosed with POCUS ultrasound.

    Science.gov (United States)

    Alonso, Joaquín Valle; Chowdhury, Motiur; Borakati, Raju; Gankande, Upali

    2017-12-01

    Swimming Induced Pulmonary Edema, or SIPE, is an emerging condition occurring in otherwise healthy individuals during surface swimming or diving that is characterized by cough, dyspnea, hemoptysis, and hypoxemia. It is typically found in those who spend time in cold water exercise with heavy swimming and surface swimming, such as civilian training for iron Man, triathalon, and military training. We report the case of a highly trained young female swimmer in excellent cardiopulmonary health, who developed acute alveolar pulmonary oedema in an open water swimming training diagnosed in the emergency department using POCUS ultrasound. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Investigations on UCS-CS mediation in radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Burns, T.C.

    1974-01-01

    Groups of 8 male Sprague-Dawley rats were used in an investigation of procaine and dimenhydrinate effects on radiation-induced taste aversion learning. Neither the local anesthetic procaine, administered intraperitoneally, nor the antinausea drug dimenhydrinate, administered intramuscularly, blocked acquisition of aversion to saccharin flavored water. Control animals confirmed that saccharin preferences appeared normally in non-irradiated animals, and that the drugs produced no aversion in the absence of radiation. Another investigation, using groups of 5 female Sprague-Dawley rats, showed a failure of dimenhydrinate in blocking the acquisition of a rotation-induced conditioned taste aversion. Two dose levels of the drug were used, 1 mg/kg and 2 mg/kg. At the dimenhydrinate dosage used in the study involving radiation (1.75 mg/kg) and at the higher dosage used in the study involving rotation, there appeared to be a potentiation of the effects of radiation and rotation, respectively. Results of these studies seem to favor a model for UCS-CS mediation as being diffuse and perhaps redundant. The possibility that nausea-producing stimuli may work synergistically was also discussed. (U.S.)

  12. Extreme Wave-Induced Oscillation in Paradip Port Under the Resonance Conditions

    Science.gov (United States)

    Kumar, Prashant; Gulshan

    2017-12-01

    A mathematical model is constructed to analyze the long wave-induced oscillation in Paradip Port, Odisha, India under the resonance conditions to avert any extreme wave hazards. Boundary element method (BEM) with corner contribution is utilized to solve the Helmholtz equation under the partial reflection boundary conditions. Furthermore, convergence analysis is also performed for the boundary element scheme with uniform and non-uniform discretization of the boundary. The numerical scheme is also validated with analytic approximation and existing studies based on harbor resonance. Then, the amplification factor is estimated at six key record stations in the Paradip Port with multidirectional incident waves and resonance modes are also estimated at the boundary of the port. Ocean surface wave field is predicted in the interior of Paradip Port for the different directional incident wave at various resonance modes. Moreover, the safe locations in the port have been identified for loading and unloading of moored ship with different resonance modes and directional incident waves.

  13. Radiation induced deep level defects in bipolar junction transistors under various bias conditions

    International Nuclear Information System (INIS)

    Liu, Chaoming; Yang, Jianqun; Li, Xingji; Ma, Guoliang; Xiao, Liyi; Bollmann, Joachim

    2015-01-01

    Bipolar junction transistor (BJT) is sensitive to ionization and displacement radiation effects in space. In this paper, 35 MeV Si ions were used as irradiation source to research the radiation damage on NPN and PNP bipolar transistors. The changing of electrical parameters of transistors was in situ measured with increasing irradiation fluence of 35 MeV Si ions. Using deep level transient spectroscopy (DLTS), defects in the bipolar junction transistors under various bias conditions are measured after irradiation. Based on the in situ electrical measurement and DLTS spectra, it is clearly that the bias conditions can affect the concentration of deep level defects, and the radiation damage induced by heavy ions.

  14. Hypercholesterolemia induces adipose dysfunction in conditions of obesity and nonobesity.

    Science.gov (United States)

    Aguilar, David; Fernandez, Maria Luz

    2014-09-01

    It is well known that hypercholesterolemia can lead to atherosclerosis and coronary heart disease. Adipose tissue represents an active endocrine and metabolic site, which might be involved in the development of chronic disease. Because adipose tissue is a key site for cholesterol metabolism and the presence of hypercholesterolemia has been shown to induce adipocyte cholesterol overload, it is critical to investigate the role of hypercholesterolemia on normal adipose function. Studies in preadipocytes revealed that cholesterol accumulation can impair adipocyte differentiation and maturation by affecting multiple transcription factors. Hypercholesterolemia has been observed to cause adipocyte hypertrophy, adipose tissue inflammation, and disruption of endocrine function in animal studies. Moreover, these effects can also be observed in obesity-independent conditions as confirmed by clinical trials. In humans, hypercholesterolemia disrupts adipose hormone secretion of visfatin, leptin, and adiponectin, adipokines that play a central role in numerous metabolic pathways and regulate basic physiologic responses such as appetite and satiety. Remarkably, treatment with cholesterol-lowering drugs has been shown to restore adipose tissue endocrine function. In this review the role of hypercholesterolemia on adipose tissue differentiation and maturation, as well as on hormone secretion and physiologic outcomes, in obesity and non–obesity conditions is presented.

  15. Assurance of Fault Management: Risk-Significant Adverse Condition Awareness

    Science.gov (United States)

    Fitz, Rhonda

    2016-01-01

    Fault Management (FM) systems are ranked high in risk-based assessment of criticality within flight software, emphasizing the importance of establishing highly competent domain expertise to provide assurance for NASA projects, especially as spaceflight systems continue to increase in complexity. Insight into specific characteristics of FM architectures seen embedded within safety- and mission-critical software systems analyzed by the NASA Independent Verification Validation (IVV) Program has been enhanced with an FM Technical Reference (TR) suite. Benefits are aimed beyond the IVV community to those that seek ways to efficiently and effectively provide software assurance to reduce the FM risk posture of NASA and other space missions. The identification of particular FM architectures, visibility, and associated IVV techniques provides a TR suite that enables greater assurance that critical software systems will adequately protect against faults and respond to adverse conditions. The role FM has with regard to overall asset protection of flight software systems is being addressed with the development of an adverse condition (AC) database encompassing flight software vulnerabilities.Identification of potential off-nominal conditions and analysis to determine how a system responds to these conditions are important aspects of hazard analysis and fault management. Understanding what ACs the mission may face, and ensuring they are prevented or addressed is the responsibility of the assurance team, which necessarily should have insight into ACs beyond those defined by the project itself. Research efforts sponsored by NASAs Office of Safety and Mission Assurance defined terminology, categorized data fields, and designed a baseline repository that centralizes and compiles a comprehensive listing of ACs and correlated data relevant across many NASA missions. This prototype tool helps projects improve analysis by tracking ACs, and allowing queries based on project, mission

  16. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Dreyer, Jean-Luc

    2014-01-01

    We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

  17. Living conditions, contraceptive use and the choice of induced abortion among pregnant women in Denmark

    DEFF Research Database (Denmark)

    Rasch, Vibeke; Wielandt, Hanne; Knudsen, Lisbeth B

    2002-01-01

    AIMS: This study describes women with induced abortion and thereby elucidates how living conditions and contraceptive failure are associated with the choice of induced abortion in a population of Danish pregnant women. METHODS: The study population consisted of pregnant women attending Odense...... University Hospital. They were categorized in two groups: women with induced abortion (n = 373) and a reference group consisting of women with spontaneous abortion and antenatal care attendees (n = 2,176). The two groups were compared by use of a case-referent design. The variables studied comprise age......, number of children, partner relationship, education, occupation, economical situation, and contraceptive use. RESULTS: Being single, aged 15-24 or 35 and above, having either no children or two or more children, and the experience of contraceptive failure were parameters which were associated...

  18. Independencies Induced from a Graphical Markov Model After Marginalization and Conditioning: The R Package ggm

    Directory of Open Access Journals (Sweden)

    Giovanni M. Marchetti

    2006-02-01

    Full Text Available We describe some functions in the R package ggm to derive from a given Markov model, represented by a directed acyclic graph, different types of graphs induced after marginalizing over and conditioning on some of the variables. The package has a few basic functions that find the essential graph, the induced concentration and covariance graphs, and several types of chain graphs implied by the directed acyclic graph (DAG after grouping and reordering the variables. These functions can be useful to explore the impact of latent variables or of selection effects on a chosen data generating model.

  19. Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

    Science.gov (United States)

    Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

    2016-02-01

    Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

  20. Conditions for accretion-induced collapse of white dwarfs

    International Nuclear Information System (INIS)

    Nomoto, Kenichi; Kondo, Yoji

    1991-01-01

    Recent discovery of an unexpectedly large number of low-mass binary pulsars (LMBPs) in globular clusters has instigated active discussions on the evolutionary origin of binary pulsars. Prompted by the possibility that at least some of LMBPs originate from accretion-induced collapse (AIC) of white dwarfs, a reexamination is conducted as to whether or not AIC occurs for the new models of O + Ne + Mg white dwarfs and solid C + O white dwarfs that can ignite explosive nuclear burning at significantly lower central densities than in the previous models. Even with low critical densities, AIC is still much more likely than explosion for both types of white dwarfs. Possible regions for AIC are presented in a diagram of mass accretion rate vs initial mass of the white dwarfs. 42 refs

  1. Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.

    1983-01-01

    A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning

  2. Biomechanical balance response during induced falls under dual task conditions in people with knee osteoarthritis.

    Science.gov (United States)

    Levinger, Pazit; Nagano, Hanatsu; Downie, Calum; Hayes, Alan; Sanders, Kerrie M; Cicuttini, Flavia; Begg, Rezaul

    2016-07-01

    People with knee osteoarthritis (OA) are at twice the risk of falling compared to older people without knee OA, however the mechanism for this is poorly understood. This study investigated the biomechanical response of the trunk and lower limb joints during a forward induced fall under different task conditions in people with and without knee OA. Twenty-four participants with OA (68.6±6.2 years) and 15 asymptomatic controls (72.4±4.8 years) participated in the study. Forward fall was induced by releasing participants from a static forward leaning position. Participants were required to recover balance during three conditions: normal, physical (obstacle clearance) and cognitive dual tasks (counting backwards). Spatiotemporal parameters, lower limb joint kinematics and kinetics of the recovery limb were compared between the two groups and across the three task conditions. The OA group demonstrated slower spatio-temporal characteristics and reduced hip and knee flexion angles, joint moments/powers and reduced muscle negative work at the knee and ankle (pfall, participants with OA demonstrated difficulty in absorbing the impact and slowing down the forward momentum of the body during a recovery step. Moreover, poor dynamic postural control was demonstrated as task complexity increased. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

    Science.gov (United States)

    Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

    2012-01-01

    The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

  4. Generalization of conditioned suppression during salicylate-induced phantom auditory perception in rats.

    Science.gov (United States)

    Brennan, J F; Jastreboff, P J

    1991-01-01

    Tonal frequency generalization was examined in a total of 114 pigmented male rats, 60 of which were tested under the influence of salicylate-induced phantom auditory perception, introduced before or after lick suppression training. Thirty control subjects received saline injections, and the remaining 24 subjects served as noninjected controls of tonal background effects on generalization. Rats were continuously exposed to background noise alone or with a superimposed tone. Offset of background noise alone (Experiment I), or combined with onset or continuation of the tone (Experiments II and III) served as the conditioned stimulus (CS). In Experiment I, tone presentations were introduced only after suppression training. Depending on the time of salicylate introduction, a strong and differential influence on generalization gradients was observed, which is consistent with subjects' detection of salicylate-induced, high-pitched sound. Moreover, when either 12- or 3 kHz tones were introduced before or after Pavlovian training to mimic salicylate effects in 24 rats, the distortions in generalization gradients resembled trends obtained from respective salicylate injected groups. Experiments II and III were aimed at evaluating the masking effect of salicylate-induced phantom auditory perception on external sounds, with a 5- or a 10-kHz tone imposed continuously on the noise or presented only during the CS. Tests of tonal generalization to frequencies ranging from 4- to 11- kHz showed that in this experimental context salicylate-induced perception did not interfere with the dominant influence of external tones, a result that further strengthens the conclusion of Experiment I.

  5. Somatosensory cortices are required for the acquisition of morphine-induced conditioned place preference.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Meng

    Full Text Available BACKGROUND: Sensory system information is thought to play an important role in drug addiction related responses. However, how somatic sensory information participates in the drug related behaviors is still unclear. Many studies demonstrated that drug addiction represents a pathological usurpation of neural mechanisms of learning and memory that normally relate to the pursuit of rewards. Thus, elucidate the role of somatic sensory in drug related learning and memory is of particular importance to understand the neurobiological mechanisms of drug addiction. PRINCIPAL FINDINGS: In the present study, we investigated the role of somatosensory system in reward-related associative learning using the conditioned place preference model. Lesions were made in somatosensory cortices either before or after conditioning training. We found that lesion of somatosensory cortices before, rather than after morphine conditioning impaired the acquisition of place preference. CONCLUSION: These results demonstrate that somatosensory cortices are necessary for the acquisition but not retention of morphine induced place preference.

  6. Fragile X Mental Retardation Protein Is Required to Maintain Visual Conditioning-Induced Behavioral Plasticity by Limiting Local Protein Synthesis.

    Science.gov (United States)

    Liu, Han-Hsuan; Cline, Hollis T

    2016-07-06

    Fragile X mental retardation protein (FMRP) is thought to regulate neuronal plasticity by limiting dendritic protein synthesis, but direct demonstration of a requirement for FMRP control of local protein synthesis during behavioral plasticity is lacking. Here we tested whether FMRP knockdown in Xenopus optic tectum affects local protein synthesis in vivo and whether FMRP knockdown affects protein synthesis-dependent visual avoidance behavioral plasticity. We tagged newly synthesized proteins by incorporation of the noncanonical amino acid azidohomoalanine and visualized them with fluorescent noncanonical amino acid tagging (FUNCAT). Visual conditioning and FMRP knockdown produce similar increases in FUNCAT in tectal neuropil. Induction of visual conditioning-dependent behavioral plasticity occurs normally in FMRP knockdown animals, but plasticity degrades over 24 h. These results indicate that FMRP affects visual conditioning-induced local protein synthesis and is required to maintain the visual conditioning-induced behavioral plasticity. Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Exaggerated dendritic protein synthesis resulting from loss of fragile X mental retardation protein (FMRP) is thought to underlie cognitive deficits in FXS, but no direct evidence has demonstrated that FMRP-regulated dendritic protein synthesis affects behavioral plasticity in intact animals. Xenopus tadpoles exhibit a visual avoidance behavior that improves with visual conditioning in a protein synthesis-dependent manner. We showed that FMRP knockdown and visual conditioning dramatically increase protein synthesis in neuronal processes. Furthermore, induction of visual conditioning-dependent behavioral plasticity occurs normally after FMRP knockdown, but performance rapidly deteriorated in the absence of FMRP. These studies show that FMRP negatively regulates local protein synthesis and is required to maintain visual conditioning-induced

  7. Clinical significance of exercise induced ST segment depression after successful percutaneous transluminal coronary angioplasty

    International Nuclear Information System (INIS)

    Aoki, Toshikazu; Konishi, Tokuji; Futagami, Yasuo

    1989-01-01

    To evaluate the clinical significance of ST segment depression during repeated Treadmill exercise after successful PTCA, Thallium-201 SPECT was performed. The Thallium-201 SPECT was performed before, one week after and 3-6 months after PTCA. All thirty-five patients had one vessel disease and positive Thallium-201 exercise test. During follow-up period for 3-6 months, 11 of 35 patients had persistent ST segment depression. Restenosis of dilated coronary lesion was demonstrated in 6 of 11 patients. In another 3 of 35 patients, exercise induced ST segment depression was disappered during follow-up Treadmill exercise. In 14 patients with persistent or transient ST segment depression after PTCA, Thallium-201 SPECT demonstrated transient ischemia in 5 of 6 patients with restenosis. In other 8 patients without restenosis, SPECT images did not demonstrate myocardial ischemia and coronary arteriographic findings could not verify side branch stenosis or intimal dissection which might cause myocardial ischemia. The etiology of ST segment depression after successful PTCA in one vessel disease is not produced by exercise induced myocardial ischemia but still unknown mechanisms may be present. (author)

  8. The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

    Science.gov (United States)

    Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

    2008-04-01

    Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

  9. The significance of the pilot conditioning plant (PKA) for spent fuel management

    International Nuclear Information System (INIS)

    Willax, H.O.

    1996-01-01

    The pilot conditioning plant (PKA) is intended as a multi-purpose facility and thus may serve various purposes involved in the conditioning or disposal of spent fuel elements or radwaste. Its design as a pilot plant permits development and trial of various methods and processes for fuel element conditioning, as well as for radwaste conditioning. (orig./DG) [de

  10. NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference123

    Science.gov (United States)

    Tokarski, Krzysztof; Bobula, Bartosz; Zygmunt, Magdalena; Smutek, Magdalena; Kamińska, Katarzyna; Gołembiowska, Krystyna; Hess, Grzegorz; Przewlocki, Ryszard

    2016-01-01

    Abstract Plasticity of the brain’s dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1D1CreERT2 mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1D1CreERT2 mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general. PMID:27294197

  11. Staurosporine induces necroptotic cell death under caspase-compromised conditions in U937 cells.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna A Dunai

    Full Text Available For a long time necrosis was thought to be an uncontrolled process but evidences recently have revealed that necrosis can also occur in a regulated manner. Necroptosis, a type of programmed necrosis is defined as a death receptor-initiated process under caspase-compromised conditions. The process requires the kinase activity of receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3 and mixed lineage kinase domain-like protein (MLKL, as a substrate of RIPK3. The further downstream events remain elusive. We applied known inhibitors to characterize the contributing enzymes in necroptosis and their effect on cell viability and different cellular functions were detected mainly by flow cytometry. Here we report that staurosporine, the classical inducer of intrinsic apoptotic pathway can induce necroptosis under caspase-compromised conditions in U937 cell line. This process could be hampered at least partially by the RIPK1 inhibitor necrotstin-1 and by the heat shock protein 90 kDa inhibitor geldanamycin. Moreover both the staurosporine-triggered and the classical death ligand-induced necroptotic pathway can be effectively arrested by a lysosomal enzyme inhibitor CA-074-OMe and the recently discovered MLKL inhibitor necrosulfonamide. We also confirmed that the enzymatic role of poly(ADP-ribosepolymerase (PARP is dispensable in necroptosis but it contributes to membrane disruption in secondary necrosis. In conclusion, we identified a novel way of necroptosis induction that can facilitate our understanding of the molecular mechanisms of necroptosis. Our results shed light on alternative application of staurosporine, as a possible anticancer therapeutic agent. Furthermore, we showed that the CA-074-OMe has a target in the signaling pathway leading to necroptosis. Finally, we could differentiate necroptotic and secondary necrotic processes based on participation of PARP enzyme.

  12. Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Liu, Lifang; Zhang, Yiming; Liu, Zihe

    2015-01-01

    Oxygen is important for normal aerobic metabolism, as well as for protein production where it is needed for oxidative protein folding. However, several studies have reported that anaerobic conditions seem to be more favorable in terms of recombinant protein production. We were interested in incre......Oxygen is important for normal aerobic metabolism, as well as for protein production where it is needed for oxidative protein folding. However, several studies have reported that anaerobic conditions seem to be more favorable in terms of recombinant protein production. We were interested...... in increasing recombinant protein production under aerobic conditions so we focused on Rox1p regulation. Rox1p is a transcriptional regulator, which in oxidative conditions represses genes induced in hypoxia. We deleted ROX1 and studied the effects on the production of recombinant proteins in Saccharomyces...

  13. Abscisic Acid and Cytokinin-Induced Osmotic and Antioxidant Regulation in Two Drought-Tolerant and Drought-Sensitive Cultivars of Wheat During Grain Filling Under Water Deficit in Field Conditions

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza SARAFRAZ-ARDAKANI

    2014-09-01

    Full Text Available Phytohormones play critical roles in regulating plant responses to stress. The present study investigates the effect of cytokinin, abscisic acid and cytokinin/abscisic acid interaction on some osmoprotectants and antioxidant parameters induced by drought stress in two wheat cultivars (Triticum aestivum L. of ‘Pishgam’ and ‘MV-17’ as tolerant and sensitive to drought during post-anthesis phase, respectively grown in field conditions. The most considerable effect of the treatments was exhibited 21 days after anthesis. Under drought conditions, the flag leaf soluble carbohydrate content increased in both cultivars while starch content was remarkably decreased in ‘Pishgam’ as compared to ‘MV-17’. Abscisic acid increased total soluble sugar and reduced starch more than other hormonal treatments, although it decreased studied monosaccharaides in ‘Pishgam’, especially. Drought stress induced high proportion of gylycinebetain and free proline in ‘Pishgam’ cultivar. Application of abscisic acid and cytokinin/abscisic acid interaction increased gylycinebetain and proline content in both cultivars under irrigation and drought conditions. The tolerant cultivar exhibited less accumulation of hydrogen peroxide and malondialdehyde in relation to significant increase of catalase and peroxidase activities and α-tocpherol content under drought conditions. All hormonal treatments increased the named enzyme activities under both irrigation and drought conditions, while higher accumulation of α-tocopherol was only showed in case of cytokinin application. Also, abscisic acid and cytokinin/abscisic acid could decrease drought-induced hydrogen peroxide and malondialdehyde level to some extent, although abscisic acid increased both of hydrogen peroxide andmalondialdehyde content in irrigation phase, especially.

  14. Cocaine induces state-dependent learning of sexual conditioning in male Japanese quail.

    Science.gov (United States)

    Gill, Karin E; Rice, Beth Ann; Akins, Chana K

    2015-01-01

    State dependent learning effects have been widely studied in a variety of drugs of abuse. However, they have yet to be studied in relation to sexual motivation. The current study investigated state-dependent learning effects of cocaine in male Japanese quail (Coturnix japonica) using a sexual conditioning paradigm. Cocaine-induced state-dependent learning effects were investigated using a 2×2 factorial design with training state as one factor and test state as the other factor. During a 14-day training phase, male quail were injected once daily with 10mg/kg cocaine or saline and then placed in a test chamber after 15min. In the test chamber, sexual conditioning trials consisted of presentation of a light conditioned stimulus (CS) followed by sexual reinforcement. During the state dependent test, half of the birds received a shift in drug state from training to testing (Coc→Sal or Sal→Coc) while the other half remained in the same drug state (Coc→Coc or Sal→Sal). Results showed that male quail that were trained and tested in the same state (Coc→Coc or Sal→Sal) showed greater sexual conditioning than male quail that were trained and tested in different states (Sal→Coc) except when cocaine was administered chronically prior to the test (Coc→Sal). For the latter condition, sexual conditioning persisted from cocaine training to the saline test. The findings suggest that state dependent effects may alter sexual motivation and that repeated exposure to cocaine during sexual activity may increase sexual motivation which, in turn, may lead to high risk sexual activities. An alternative explanation for the findings is also discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.

    Science.gov (United States)

    Aguilar, M A; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J

    2015-04-01

    Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats.

    Science.gov (United States)

    Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

    2018-06-01

    Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA B receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA B receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA B receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA B receptor. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Ferulic Acid, But Not All Hydroxycinnamic Acids, Is a Novel T3SS Inducer of Ralstonia solanacearum and Promotes Its Infection Process in Host Plants under Hydroponic Condition

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2017-09-01

    Full Text Available Hydroxycinnamic acids (HCAs are typical monocyclic phenylpropanoids, including cinnamic acid (Cin, coumaric acid (Cou, caffeic acid (Caf, ferulic acid (FA and their isomers, and involved in the interactions between pathogens and host plants. Here, we focused on the impact of HCAs on expression of type III secretion system (T3SS in Ralstonia solanacearum. FA significantly induced the expression of the T3SS and some type III effectors (T3Es genes in hrp-inducing medium, while did not the other HCAs. However, exogenously supplemented FA did not affect the T3SS expression in planta and the elicitation of the hypersensitive response (HR in tobacco leaves. Consistent with its central roles in pathogenicity, the FA-induced expression of the T3SS led to significant promotion on infection process of R. solanacearum in tomato plants under hydroponics cultivation. Moreover, the FA-induced expression of the T3SS was specifically mediated by the well-characterized signaling cascade PrhA-prhI/R-PrhJ-HrpG-HrpB, independent of the other known regulatory pathways. In summary, our results demonstrated that FA, a novel inducer of the T3SS in R. solanacearum, was able to promote its infection process in host plants under hydroponics condition.

  18. Composite mechanism of the Büyükçekmece (Turkey) landslide as conditioning factor for earthquake-induced mobility

    Science.gov (United States)

    Martino, S.; Lenti, L.; Bourdeau, C.

    2018-05-01

    Earthquake-induced displacements of landslides are significantly conditioned by their 1D and 2D interactions with seismic waves, as currently proven by several studies. Nevertheless, the role of a more complex geological setting, responsible for a heterogeneous composition of the landslide mass, can significantly influence these phenomena. The heterogeneity can also depend on multiple phases of the landslide activity, responsible for dislodging the whole landslide mass into submasses, each one delimited by secondary scarps and characterized by individual mobility. Hence, in the framework of the European project "MARSite - Marmara Supersite: new directions in seismic hazard assessment through focused Earth observation in the Marmara Supersite", the Büyükçekmece landslide, located approximately 30 km W of Istanbul (Turkey), was considered as a case study. This landslide involves a large mass of approximately 140 million cubic metres, composed of silty clays, tuffs and sands ascribable to Cenozoic geological formations. The landslide is characterized by multiple phases of activity with a composite rototranslational mechanism, which created seven submasses delimited by secondary scarps. The scheme of water circulation in the landslide slope, based on piezometer data as well as on a geological survey, accounts for two flow nets: the first, shallower flow net is located in superficial sandy deposits, outcropping in the dislodged landslide submasses; the second, deeper flow net is located in the main sliding surface. A slope stability analysis following a global limit equilibrium approach provided a distribution of the pseudostatic coefficient vs. pore water pressure. The results show that the stability of the landslide submasses increases moving downslope, and reactivations are expected in the case of earthquakes with a return period between 475 and 2475 yr, according to the local seismic hazard. Dynamic numerical modelling was also performed using the stress

  19. DETERMINATION OF MOST SIGNIFICANT FACTORS FOR ANALYSIS OF HIGHWAY OPERATING CONDITIONS

    Directory of Open Access Journals (Sweden)

    M. G. Solodkaya

    2017-01-01

    Full Text Available Traffic circulation on highways is a random process. Therefore automotive damage rate and, respectively, roads on which they are moving is subjected to regularities of random processes. Dynamic processes of vehicle-road interaction are determined to various extents by a host of factors that include road pavement evenness and characteristics of moving vehicles. For this reason the following task has been set: to reveal the most significant factors and mathematically correlate values of vehicle dynamic loads with a quality of road pavement and vehicle speed. Such task statement has not been solved adequately and this situation determines importance and novelty of the investigations in the given direction. While solving the mentioned task the investigations which have been carried out under real-life conditions and with the help of real-life objects are considered as the most reliable ones. However, preparation and execution of such experiments as needed significantly complicates their implementation. In this regard it looks rather expediential to combine a factorial experiment with the tests of a checked model while using ECM with stage-by-stage parameter fixation of working processes passing in “vehicle-road” system, comprehensive assessment pertaining to influence of the selected factors and selection of their optimum combination. Mathematical dependence has been obtained to evaluate influence of several external factors on optimization of vehicle dynamic load on the road. This component makes it possible to attain a simplified and adequate description of element interaction in “vehicle – road” system. While investigating influence of pavement irregularities on maximum dynamic loads on the road influence rate of the selected factors is determined in the following sequence: vehicle weight, pavement evenness and speed of transport facility.

  20. Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated by distinct GABAA receptor subtypes in mice

    Science.gov (United States)

    Smith, Kiersten S.; Engin, Elif; Meloni, Edward G.; Rudolph, Uwe

    2012-01-01

    GABAA receptor modulating drugs such as benzodiazepines (BZs) have been used to treat anxiety disorders for over five decades. In order to determine whether the same or different GABAA receptor subtypes are necessary for the anxiolytic-like action of BZs in unconditioned anxiety and conditioned fear models, we investigated the role of different GABAA receptor subtypes by challenging wild type, α1(H101R), α2(H101R) and α3(H126R) mice bred on the C57BL/6J background with diazepam or chlordiazepoxide in the elevated plus maze and the fear-potentiated startle paradigms. Both drugs significantly increased open arm exploration in the elevated plus maze in wild type, α1(H101R) and α3(H126R), but this effect was abolished in α2(H101R) mice; these were expected results based on previous published results. In contrast, while administration of diazepam and chlordiazepoxide significantly attenuated fear-potentiated startle (FPS) in wild type mice and α3(H126R) mice, the fear-reducing effects of these drugs were absent in both α1(H101R) and α2(H101R) point mutants, indicating that both α1- and α2-containing GABAA receptors are necessary for BZs to exert their effects on conditioned fear responses.. Our findings illustrate both an overlap and a divergence between the GABAA receptor subtype requirements for the impact of BZs, specifically that both α1- and α2-containing GABAA receptors are necessary for BZs to reduce conditioned fear whereas only α2-containing GABAA receptors are needed for BZ-induced anxiolysis in unconditioned tests of anxiety. This raises the possibility that GABAergic pharmacological interventions for specific anxiety disorders can be differentially tailored. PMID:22465203

  1. Influence of contact conditions on vibration induced wear of metals

    International Nuclear Information System (INIS)

    Hofmann, P.J.; Schettler, T.; Wieling, N.; Steininger, D.A.

    1990-01-01

    Unfavourable design characteristics of nuclear power plant steam generators and heat exchangers in general may result in vibration induced tube wear. A systematic investigation was performed on the contact conditions which may appear between heat exchanger tubes and tube support structure and the influence of different parameters e.g., normal contact force, on the resulting steady state wear rates. It is concluded that not only are contact forces and sliding distances important in the wear process but also the type of relative motion has a decisive influence on the resulting wear rates. For a certain 'work rate', the wear rate caused by repeated impact motions between tube and tube support structure may be an order of magnitude higher than that caused by only sliding motion. This is the result of different operating wear mechanisms which are discussed in this paper. (orig.)

  2. Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.

    Science.gov (United States)

    Bryant, Camron D; Kole, Loren A; Guido, Michael A; Cheng, Riyan; Palmer, Abraham A

    2012-01-01

    The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.

  3. Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Imai, Yosuke; Petersen, Kristian Kjær

    2016-01-01

    This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar...... forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive...... signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers....

  4. The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

    Science.gov (United States)

    Fox, Robert A.; Sutton, R. L.; Mckenna, Susan

    1991-01-01

    Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

  5. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

    Directory of Open Access Journals (Sweden)

    Lingling Han

    2015-01-01

    Full Text Available This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA- induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4, AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase (ACC, and uncoupling protein 3 (UCP3 were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, P<0.05 and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, P<0.05. The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all P<0.05, but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all P<0.05. In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

  6. Systemic 5-Bromo-2-Deoxyuridine Induces Conditioned Flavor Aversion and C-Fos in the Visceral Neuraxis

    Science.gov (United States)

    Kimbrough, Adam; Kwon, Bumsup; Eckel, Lisa A.; Houpt, Thomas A.

    2011-01-01

    5-bromo-2-deoxyuridine (BrdU) is often used in studies of adult neurogenesis and olfactory learning, but it can also have toxic effects on highly proliferative tissue. We found that pairing Kool-Aid flavors with acute systemic injections of BrdU induced strong conditioned flavor aversions. Intermittent injections during Kool-Aid-glucose…

  7. Rhodiola rosea Impairs Acquisition and Expression of Conditioned Place Preference Induced by Cocaine

    OpenAIRE

    Federica Titomanlio; Carmen Manzanedo; Marta Rodríguez-Arias; Laura Mattioli; Marina Perfumi; José Miñarro; María A. Aguilar

    2013-01-01

    A novel approach to the treatment of adverse effects of drugs of abuse is one which makes use of natural products. The present study investigated the effect of Rhodiola rosea L. hydroalcoholic extract (RHO) on cocaine-induced hyperactivity and conditioned place preference (CPP) in mice. In a first experiment, mice received RHO (15, 20 or 25?mg/kg, IG), cocaine (25?mg/kg, i.p.) (COC), or a combination of both drugs (COC + RHO15, COC + RHO20, and COC + RHO25), and their locomotor activity was e...

  8. Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

    Science.gov (United States)

    García-Pardo, M P; Blanco-Gandía, M C; Valiente-Lluch, M; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

    2015-12-03

    Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Studies on the role of central histamine in the acquisition of a radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1982-01-01

    The experiments described in this report were designed to test two hypotheses about how exposure to low-level radiation can affect the behavior of an organism: first, tht radiation effects on behavior are mediated by a radiation-induced release of histamine; and second, that this radiation-induced histamine release can exert relatively direct effects on the central nervous system. The results of the first experiment showed that microinjection of histamine directly into the fourth ventricle of rats produced a taste aversion to a novel sucrose solution. Pretreating rats with intraventricular H 1 or H 2 blockers was not effective in preventing the acquisition of the radiation-induced aversion, although the H 1 blocker did prevent the acquisition of a histamine-induced taste aversion. It also was not possible to establish a cross-tolerance between centrally administered histamine and radiation. The results are interpreted as not supporting the hypothesis that a radiation-induced release of central histamine mediates the acquisition of a conditioned taste aversion following exposure to low-level radiation

  10. The Selective D3 Receptor Antagonist SB277011A Attenuates Morphine-Triggered Reactivation of Expression of Cocaine-Induced Conditioned Place Preference

    Science.gov (United States)

    Rice, Onarae V.; Heidbreder, Christian A.; Gardner, Eliot L.; Schonhar, Charles D.; Ashby, Charles R.

    2014-01-01

    We examined the effect of acute administration of the selective D3 receptor antagonist SB277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB277011 decreases the incentive motivational actions of morphine. The present findings suggest that central D3 dopamine receptors are involved in relapse to cocaine-seeking behavior that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D3 receptor antagonists constitute promising compounds for treating addiction. PMID:23404528

  11. Microfluidic perfusion culture of human induced pluripotent stem cells under fully defined culture conditions.

    Science.gov (United States)

    Yoshimitsu, Ryosuke; Hattori, Koji; Sugiura, Shinji; Kondo, Yuki; Yamada, Rotaro; Tachikawa, Saoko; Satoh, Taku; Kurisaki, Akira; Ohnuma, Kiyoshi; Asashima, Makoto; Kanamori, Toshiyuki

    2014-05-01

    Human induced pluripotent stem cells (hiPSCs) are a promising cell source for drug screening. For this application, self-renewal or differentiation of the cells is required, and undefined factors in the culture conditions are not desirable. Microfluidic perfusion culture allows the production of small volume cultures with precisely controlled microenvironments, and is applicable to high-throughput cellular environment screening. Here, we developed a microfluidic perfusion culture system for hiPSCs that uses a microchamber array chip under defined extracellular matrix (ECM) and culture medium conditions. By screening various ECMs we determined that fibronectin and laminin are appropriate for microfluidic devices made out of the most popular material, polydimethylsiloxane (PDMS). We found that the growth rate of hiPSCs under pressure-driven perfusion culture conditions was higher than under static culture conditions in the microchamber array. We applied our new system to self-renewal and differentiation cultures of hiPSCs, and immunocytochemical analysis showed that the state of the hiPSCs was successfully controlled. The effects of three antitumor drugs on hiPSCs were comparable between microchamber array and 96-well plates. We believe that our system will be a platform technology for future large-scale screening of fully defined conditions for differentiation cultures on integrated microfluidic devices. © 2013 Wiley Periodicals, Inc.

  12. Spike timing rigidity is maintained in bursting neurons under pentobarbital-induced anesthetic conditions

    Directory of Open Access Journals (Sweden)

    Risako Kato

    2016-11-01

    Full Text Available Pentobarbital potentiates γ-aminobutyric acid (GABA-mediated inhibitory synaptic transmission by prolonging the open time of GABAA receptors. However, it is unknown how pentobarbital regulates cortical neuronal activities via local circuits in vivo. To examine this question, we performed extracellular unit recording in rat insular cortex under awake and anesthetic conditions. Not a few studies apply time-rescaling theorem to detect the features of repetitive spike firing. Similar to these methods, we define an average spike interval locally in time using random matrix theory (RMT, which enables us to compare different activity states on a universal scale. Neurons with high spontaneous firing frequency (> 5 Hz and bursting were classified as HFB neurons (n = 10, and those with low spontaneous firing frequency (< 10 Hz and without bursting were classified as non-HFB neurons (n = 48. Pentobarbital injection (30 mg/kg reduced firing frequency in all HFB neurons and in 78% of non-HFB neurons. RMT analysis demonstrated that pentobarbital increased in the number of neurons with repulsion in both HFB and non-HFB neurons, suggesting that there is a correlation between spikes within a short interspike interval. Under awake conditions, in 50% of HFB and 40% of non-HFB neurons, the decay phase of normalized histograms of spontaneous firing were fitted to an exponential function, which indicated that the first spike had no correlation with subsequent spikes. In contrast, under pentobarbital-induced anesthesia conditions, the number of non-HFB neurons that were fitted to an exponential function increased to 80%, but almost no change in HFB neurons was observed. These results suggest that under both awake and pentobarbital-induced anesthetized conditions, spike firing in HFB neurons is more robustly regulated by preceding spikes than by non-HFB neurons, which may reflect the GABAA receptor-mediated regulation of cortical activities. Whole-cell patch

  13. Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

    Science.gov (United States)

    Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

    2014-01-01

    MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

  14. Exercise-Induced Bronchoconstriction (EIB)

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  15. Effect of induced body condition score differences on physiological response, productive and reproductive performance of Malpura ewes kept in a hot, semi-arid environment.

    Science.gov (United States)

    Sejian, V; Maurya, V P; Naqvi, S M K; Kumar, D; Joshi, A

    2010-04-01

    This study was undertaken to study the influence of induced body condition score (BCS) differences on physiological response, productive and reproductive performance of Malpura ewes to optimise BCS for these ewes for maximising production making it economically viable. The study was conducted for a period of 1 year using thirty healthy Malpura ewes (2-4 year old). The animals were randomly divided and different BCS was induced within three groups named Group I (BCS 2.5; n = 10), Group II (BCS 3.0-3.5; n = 10) and Group III (BCS 4.0; n = 10). The parameters included in the study were allometric measurements, physiological response, wool yield and reproductive performance. BCS had a significant influence on allometric measurements, respiration rate and different reproductive parameters studied, while wool production differed significantly during spring and non-significantly during autumn. The results revealed that the reproductive performance of Malpura ewes with a BCS of 3.0-3.5 was better in comparison with the groups with lower and higher BCS. It may be concluded from this study that an active management of breeding sheep flock to achieve a BCS of 3.0-3.5 may prove to result in an economically viable return from these flocks.

  16. Conditioned Side Effects Induced by Cancer Chemotherapy: Prevention Through Behavioral Treatment.

    Science.gov (United States)

    Burish, Thomas G.; And Others

    1987-01-01

    Studied cancer patients (N=24) in order to determine whether conditioned nausea and vomiting could be delayed or prevented. Indicated that patients receiving progressive muscle relaxation training and guided imagery had significantly less nausea and vomiting and significanty lower blood pressures, pulse rates, and dysphoria, especially anxiety,…

  17. Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

    Science.gov (United States)

    Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

    2016-07-01

    The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

  18. A study on the flow induced vibration in two phase flow under heating and non-heating conditions

    International Nuclear Information System (INIS)

    Kim, Dae Hun

    2007-02-01

    Critical heat flux (CHF) enhancement devices, like a spacer grid with mixing vane, cause flow-induced vibration (FIV) due to turbulence made by structural resistance. CHF enhancement and FIV reduction are usually studied separately. The main purpose of this article is to investigate the relationship between CHF and FIV. Information of flow-induced vibration due to wire coil design, is experimentally presented in this study by detecting flow-induced vibration under the two-phase flow condition with wire coil inserts. CHF experiments were performed in an upward vertical annulus tube under controlled vibration conditions to determine the effect of vibration on CHF. FIV was measured in an upward vertical tube with various wire coil inserts using air-water as flow material. CHF experiments were performed at one atmosphere with mechanically controlled vibration. A quartz tube (inner diameter of 17 mm, thickness of 2mm and length of 0.72 m) was used for outer tube and a SUS-304 tube (outer diameter of 6.35 mm, thickness of 0.89 mm and length of 0.7 m) was used for the inner heater. Vibration of the heater tube with an amplitude range of 0.1 mm to 0.5 mm and a frequency range of 10 Hz to 50 Hz was carried out at a mass flux of 115 kg/m 2 s and 215 kg/m 2 s. CHF was enhanced by vibration with a maximum ratio of 16.4 %. CHF was increased with increased amplitude and quality. The CHF correlation was developed with R (coefficient of correlation) of 0.903. FIV measuring experiments were performed at one atmosphere by changing the inserted wire coil type. An acrylic tube was used for the test section with inner diameter of 25 mm, thickness of 10 mm and length of 0.5 m. Four types of wire coil, which have a thickness of between 2 mm and 3 mm and pitch length of between 25 mm and 50 mm, were used. FIV and dynamic pressure were detected in water mass flux range of 100 ∼ 3060 kg/m 2 s and air mass flux range of 5.02 ∼ 60.3 kg/m 2 s. Vibration increased along with mass flux and

  19. Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions.

    Science.gov (United States)

    Wang, Juan; Hao, Jie; Bai, Donghui; Gu, Qi; Han, Weifang; Wang, Lei; Tan, Yuanqing; Li, Xia; Xue, Ke; Han, Pencheng; Liu, Zhengxin; Jia, Yundan; Wu, Jun; Liu, Lei; Wang, Liu; Li, Wei; Liu, Zhonghua; Zhou, Qi

    2015-11-12

    Human induced pluripotent stem cells (hiPSCs) are considered as one of the most promising seed cell sources in regenerative medicine. Now hiPSC-based clinical trials are underway. To ensure clinical safety, cells used in clinical trials or therapies should be generated under GMP conditions, and with Xeno-free culture media to avoid possible side effects like immune rejection that induced by the Xeno reagents. However, up to now there are no reports for hiPSC lines developed completely under GMP conditions using Xeno-free reagents. Clinical-grade human foreskin fibroblast (HFF) cells used as feeder cells and parental cells of the clinical-grade hiPSCs were isolated from human foreskin tissues and cultured in Xeno-free media. Clinical-grade hiPSCs were derived by integration-free Sendai virus-based reprogramming kit in Xeno-free pluriton™ reprogramming medium or X medium. Neural cells and cardiomyocytes differentiation were conducted following a series of spatial and temporal specific signals induction according to the corresponding lineage development signals. Biological safety evaluation of the clinical-grade HFF cells and hiPSCs were conducted following the guidance of the "Pharmacopoeia of the People's Republic of China, Edition 2010, Volume III". We have successfully derived several integration-free clinical-grade hiPSC lines under GMP-controlled conditions and with Xeno-free reagents culture media in line with the current guidance of international and national evaluation criteria. As for the source of hiPSCs and feeder cells, biological safety evaluation of the HFF cells have been strictly reviewed by the National Institutes for Food and Drug Control (NIFDC). The hiPSC lines are pluripotent and have passed the safety evaluation. Moreover, one of the randomly selected hiPSC lines was capable of differentiating into functional neural cells and cardiomyocytes in Xeno-free culture media. The clinical-grade hiPSC lines therefore could be valuable sources for

  20. Systemic Exercise-Induced Hypoalgesia Following Isometric Exercise Reduces Conditioned Pain Modulation.

    Science.gov (United States)

    Alsouhibani, Ali; Vaegter, Henrik Bjarke; Hoeger Bement, Marie

    2018-04-03

    Physically active individuals show greater conditioned pain modulation (CPM) compared with less active individuals. Understanding the effects of acute exercise on CPM may allow for a more targeted use of exercise in the management of pain. This study investigated the effects of acute isometric exercise on CPM. In addition, the between-session and within-session reliability of CPM was investigated. Experimental, randomized crossover study. Laboratory at Marquette University. Thirty healthy adults (19.3±1.5 years, 15 males). Subjects underwent CPM testing before and after isometric exercise (knee extension, 30% maximum voluntary contraction for three minutes) and quiet rest in two separate experimental sessions. Pressure pain thresholds (PPTs) at the quadriceps and upper trapezius muscles were assessed before, during, and after ice water immersions. PPTs increased during ice water immersion (i.e., CPM), and quadriceps PPT increased after exercise (P CPM decreased similarly following exercise and quiet rest (P > 0.05). CPM within-session reliability was fair to good (intraclass correlation coefficient [ICC] = 0.43-0.70), and the between-session reliability was poor (ICC = 0.20-0.35). Due to the variability in the systemic exercise-induced hypoalgesia (EIH) response, participants were divided into systemic EIH responders (N = 9) and nonresponders (N = 21). EIH responders experienced attenuated CPM following exercise (P = 0.03), whereas the nonresponders showed no significant change (P > 0.05). Isometric exercise decreased CPM in individuals who reported systemic EIH, suggesting activation of shared mechanisms between CPM and systemic EIH responses. These results may improve the understanding of increased pain after exercise in patients with chronic pain and potentially attenuated CPM.

  1. Bupropion induces social anxiety in adolescent mice: Influence of housing conditions.

    Science.gov (United States)

    Gómez, Carmen; Redolat, Rosa; Carrasco, Carmen

    2017-08-01

    The antidepressant bupropion has received increasing attention as a pharmacological tool to treat addiction although little is known about its effects on social behaviour in adolescents. The present study aimed to evaluate if environmental housing conditions influence bupropion's actions on social behaviour of adolescent mice. Mice were either group- or individually housed for 2-weeks and then randomly divided into 2 cohorts: half of the mice remained in the initial housing condition and the other half were changed to isolated conditions for further 2-weeks. The following groups were compared: isolated/isolated (ISO/ISO), isolated/group-housed (ISO/GR), group-housed/isolated (GR/ISO), and group-housed/group-housed (GR/GR). The effects of bupropion (40, 20, 10mg/kg) or saline on social interaction were assessed for each housing condition. Social encounters were evaluated using ethological analysis. Data showed significant effects of bupropion on grooming and digging. This drug diminished time mice allocated to these behavioural categories in all housing conditions. In ISO/GR and GR/ISO conditions, bupropion increased environmental exploration (non-social exploration and exploration from a distance), reduced social investigation and increased avoidance/flee and defence/submission behaviours. An augment of avoidance/flee during social interactions was observed in bupropion-treated mice in GR/GR housing condition. These results suggest that this drug exhibits anxiogenic-like properties in social encounters between adolescent mice, especially when a transition in housing conditions has been experienced during this period. Changes in housing conditions may be a useful model for evaluating the effects of bupropion on social behaviour and the role of environmental housing conditions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Light-induced magnetoresistance in solution-processed planar hybrid devices measured under ambient conditions.

    Science.gov (United States)

    Banerjee, Sreetama; Bülz, Daniel; Reuter, Danny; Hiller, Karla; Zahn, Dietrich R T; Salvan, Georgeta

    2017-01-01

    We report light-induced negative organic magnetoresistance (OMAR) measured in ambient atmosphere in solution-processed 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene) planar hybrid devices with two different device architectures. Hybrid electronic devices with trench-isolated electrodes (HED-TIE) having a channel length of ca. 100 nm fabricated in this work and, for comparison, commercially available pre-structured organic field-effect transistor (OFET) substrates with a channel length of 20 µm were used. The magnitude of the photocurrent as well as the magnetoresistance was found to be higher for the HED-TIE devices because of the much smaller channel length of these devices compared to the OFETs. We attribute the observed light-induced negative magnetoresistance in TIPS-pentacene to the presence of electron-hole pairs under illumination as the magnetoresistive effect scales with the photocurrent. The magnetoresistance effect was found to diminish over time under ambient conditions compared to a freshly prepared sample. We propose that the much faster degradation of the magnetoresistance effect as compared to the photocurrent was due to the incorporation of water molecules in the TIPS-pentacene film.

  3. The Effects of Acute Stress-Induced Sleep Disturbance on Acoustic Trauma-Induced Tinnitus in Rats

    Directory of Open Access Journals (Sweden)

    Yiwen Zheng

    2014-01-01

    Full Text Available Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats.

  4. Centrifuge model tests of rainfall-induced slope failures for the investigation of the initiation conditions

    Science.gov (United States)

    Matziaris, Vasileios; Marshall, Alec; Yu, Hai-Sui

    2015-04-01

    Rainfall-induced landslides are very common natural disasters which cause damage to properties and infrastructure and may result in the loss of human lives. These phenomena often take place in unsaturated soil slopes and are triggered by the saturation of the soil profile, due to rain infiltration, which leads to a loss of shear strength. The aim of this study is to determine rainfall thresholds for the initiation of landslides under different initial conditions. Model tests of rainfall-induced landslides are conducted in the Nottingham Centre for Geomechanics 50g-T geotechnical centrifuge. Initially unsaturated plane-strain slope models made with fine silica sand are prepared at varying densities at 1g and accommodated within a climatic chamber which provides controlled environmental conditions. During the centrifuge flight at 60g, rainfall events of varying intensity and duration are applied to the slope models causing the initiation of slope failure. The impact of soil state properties and rainfall characteristics on the landslide initiation process are discussed. The variation of pore water pressures within the slope before, during and after simulated rainfall events is recorded using miniature pore pressure transducers buried in the soil model. Slope deformation is determined by using a high-speed camera and digital image analysis techniques.

  5. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  6. Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population.

    Science.gov (United States)

    Johansson, Henrik; Norlander, Katarina; Berglund, Lars; Janson, Christer; Malinovschi, Andrei; Nordvall, Lennart; Nordang, Leif; Emtner, Margareta

    2015-01-01

    Exercise-induced respiratory symptoms are common among adolescents. Exercise is a known stimulus for transient narrowing of the airways, such as exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in a general population of adolescents. In this cross-sectional study, a questionnaire on exercise-induced dyspnoea was sent to all adolescents born in 1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents (99 with self-reported exercise-induced dyspnoea and 47 without this condition) underwent standardised treadmill exercise tests for EIB and EILO. The exercise test for EIB was performed while breathing dry air; a positive test was defined as a decrease of ≥10% in FEV1 from baseline. EILO was investigated using continuous laryngoscopy during exercise. The estimated prevalence of EIB and EILO in the total population was 19.2% and 5.7%, respectively. No gender differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no significant differences in body mass index, lung function, diagnosed asthma or medication between the participants with exercise-induced dyspnoea who had or did not have a positive EIB or EILO test result. Both EIB and EILO are common causes of exercise-induced dyspnoea in adolescents. EILO is equally common among girls and boys and can coexist with EIB. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Significance of settling model structures and parameter subsets in modelling WWTPs under wet-weather flow and filamentous bulking conditions.

    Science.gov (United States)

    Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen; Plósz, Benedek Gy

    2014-10-15

    Current research focuses on predicting and mitigating the impacts of high hydraulic loadings on centralized wastewater treatment plants (WWTPs) under wet-weather conditions. The maximum permissible inflow to WWTPs depends not only on the settleability of activated sludge in secondary settling tanks (SSTs) but also on the hydraulic behaviour of SSTs. The present study investigates the impacts of ideal and non-ideal flow (dry and wet weather) and settling (good settling and bulking) boundary conditions on the sensitivity of WWTP model outputs to uncertainties intrinsic to the one-dimensional (1-D) SST model structures and parameters. We identify the critical sources of uncertainty in WWTP models through global sensitivity analysis (GSA) using the Benchmark simulation model No. 1 in combination with first- and second-order 1-D SST models. The results obtained illustrate that the contribution of settling parameters to the total variance of the key WWTP process outputs significantly depends on the influent flow and settling conditions. The magnitude of the impact is found to vary, depending on which type of 1-D SST model is used. Therefore, we identify and recommend potential parameter subsets for WWTP model calibration, and propose optimal choice of 1-D SST models under different flow and settling boundary conditions. Additionally, the hydraulic parameters in the second-order SST model are found significant under dynamic wet-weather flow conditions. These results highlight the importance of developing a more mechanistic based flow-dependent hydraulic sub-model in second-order 1-D SST models in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Nutrient Availability Alters the Effect of Autophagy on Sulindac Sulfide-Induced Colon Cancer Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Shiun-Kwei Chiou

    2012-01-01

    Full Text Available Autophagy is a catabolic process by which a cell degrades its intracellular materials to replenish itself. Induction of autophagy under various cellular stress stimuli can lead to either cell survival or cell death via apoptotic and/or autophagic (nonapoptotic pathways. The NSAID sulindac sulfide induces apoptosis in colon cancer cells. Here, we show that inhibition of autophagy under serum-deprived conditions resulted in significant reductions of sulindac sulfide-induced apoptosis in HT-29 colon cancer cells. In contrast, inhibition of autophagy under conditions where serum is available significantly increased sulindac sulfide-induced apoptosis in HT-29 cells. We previously showed that the apoptosis inhibitor, survivin, plays a role in regulating NSAID-induced apoptosis and autophagic cell death. Here, we show that survivin protein half-life is increased in the presence of autophagy inhibitors under serum-deprived conditions, but not under conditions when serum is available. Thus, the increased levels of survivin may be a factor contributing to inhibition of sulindac sulfide-induced apoptosis under serum-deprived conditions. These results suggest that whether a cell lives or dies due to autophagy induction depends on the balance of factors that regulate both autophagic and apoptotic processes.

  9. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  10. Chronic Caloric Restriction and Exercise Improve Metabolic Conditions of Dietary-Induced Obese Mice in Autophagy Correlated Manner without Involving AMPK

    Directory of Open Access Journals (Sweden)

    Mingxia Cui

    2013-01-01

    Full Text Available Aim. To investigate the role of AMPK activation and autophagy in mediating the beneficial effects of exercise and caloric restriction in obesity. Methods. Dietary-induced obesity mice were made and divided into 5 groups; one additional group of normal mice serves as control. Mice in each group received different combinations of interventions including low fat diet, caloric restriction, and exercise. Then their metabolic conditions were assessed by measuring serum glucose and insulin, serum lipids, and liver function. AMPK phosphorylation and autophagy activity were detected by western blotting. Results. Obese mice models were successfully induced by high fat diet. Caloric restriction consistently improved the metabolic conditions of the obese mice, and the effects are more prominent than the mice that received only exercise. Also, caloric restriction, exercise, and low fat diet showed a synergistic effect in the improvement of metabolic conditions. Western blotting results showed that this improvement was not related with the activation of AMPK in liver, skeletal muscle, or heart but correlates well with the autophagy activity. Conclusion. Caloric restriction has more prominent beneficial effects than exercise in dietary-induced obese mice. These effects are correlated with the autophagy activity and may be independent of AMPK activation.

  11. Growth of AlGaN under the conditions of significant gallium evaporation: phase separation and enhanced lateral growth

    OpenAIRE

    Mayboroda, I. O.; Knizhnik, A. A.; Grishchenko, Yu. V.; Ezubchenko, I. S.; Zanaveskin, Maxim L.; Presniakov, M. Yu.; Potapkin, B. V.; Ilyin, V. A.

    2017-01-01

    Growth kinetics of AlGaN in NH3 MBE under significant Ga desorption was studied. It was found that the addition of gallium stimulates 2D growth and provides better morphology of films compared to pure AlN. The effect was experimentally observed at up to 98% desorption of the impinging gallium. We found that, under the conditions of significant thermal desorption, larger amounts of gallium were retained at lateral boundaries of 3D surface features than at flat terraces because of the higher bi...

  12. Short-term cortical plasticity induced by conditioning pain modulation

    DEFF Research Database (Denmark)

    Egsgaard, Line Lindhardt; Buchgreitz, Line; Wang, Li

    2012-01-01

    To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical stimulat......To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical......, and after homotopic and heterotopic CPM versus control. Peak latencies at N100, P200, and P300 were extracted and the location/strength of corresponding dipole current sources and multiple dipoles were estimated. Homotopic CPM caused hypoalgesia (P = 0.032, 30.6% compared to baseline) to electrical...... stimulation. No cortical changes were found for homotopic CPM. A positive correlation at P200 between electrical pain threshold after tonic pain and the z coordinate after tonic pain (P = 0.032) was found for homotopic CPM. For heterotopic CPM, no significant hypoalgesia was found and a dipole shift of the P...

  13. Nutritional Interventions for Cancer-induced Cachexia

    OpenAIRE

    Gullett, Norleena P.; Mazurak, Vera; Hebbar, Gautam; Ziegler, Thomas R.

    2011-01-01

    Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathol...

  14. Enhancement of laser induced damage threshold of fused silica by acid etching combined with UV laser conditioning

    International Nuclear Information System (INIS)

    Chen Meng; Xiang Xia; Jiang Yong; Zu Xiaotao; Yuan Xiaodong; Zheng Wanguo; Wang Haijun; Li Xibin; Lu Haibing; Jiang Xiaodong; Wang Chengcheng

    2010-01-01

    Acid etching combined with UV laser conditioning is developed to enhance the laser induced damage threshold (LIDT) of fused silica. Firstly, the fused silica is etched for 1 ∼ 100 min with a buffered 1% HF solution. After acid etching, its transmittance, surface roughness and LIDT are measured. The results reveal that the fused silica has the highest LIDT and transmittance after etching for 10 min. Then UV laser (355 nm) conditioning is adopted to process the 10-min-etched fused silica. When the laser fluence is below 60% of fused silica's zero probability damage threshold, the LIDT increases gradually with the increase of laser conditioning fluence. However, the LIDT rapidly decreases to be lower than the threshold of the 10-min-etched fused silica when the conditioning fluence is up to 80% of the threshold. Proper acid etching and laser conditioning parameters will effectively enhance the laser damage resistance of fused silica. (authors)

  15. The Blockade of Glutamate N-methyl-D-aspartate Receptors into the Prelimbic of Prefrontal Cortex Decreases Morphine-induced Conditioned Place Preference in Rat

    Directory of Open Access Journals (Sweden)

    Samad Javadi

    2017-12-01

    Full Text Available BACKGROUND: The prelimbic area (PL of the prefrontal cortex is susceptible to abnormal developmental stimuli that raises the risk of addiction. Glutamate receptors play a key role in opiate reinforcement and reward functions in this area. Therefore, we examined the effect of the DL-2-amino-5-phosphonopentanoic acid (AP5, as N-methyl-D-aspartate (NMDA receptor antagonist into the PL on the phases of conditioned place preference (CPP induced by morphine. METHODS: Male Wistar rats were divided into 12 groups (3 surgical groups for each dose of morphine in any phase of CPP and anaesthetized with chloral hydrate. Cannula was implanted into the PL and the AP5 was injected into this area and morphine-induced CPP was investigated. Data were processed with the commercially available SPSS 22 software using one-way ANOVA and Tukey's test. p<0.05 were considered statistically significant. RESULTS: Our findings indicated, morphine in doses of 2.5 to 10 mg/kg induced CPP. Microinjection of various doses of the AP5 into the PL before the administration of the effective dose of morphine significantly reduced place preference in the acquisition and the expression phases of the CPP test compared to the sham group (p<0.001. In another set of our experiments was seen that, different doses of the AP5 with the ineffective dose of morphine only reduced the expression phase of the CPP (p<0.001 while, produced neither preference nor aversion effect on the acquisition phase (p=0.147. CONCLUSION: It seems that the glutamate NMDA receptors in the PL through memory formation and morphine-related reward signals play a critical role in addiction process during morphine-induced CPP. KEYWORDS: N-methyl-aspartate, morphine, glutamate receptor, prefrontal cortex, reward

  16. Adolescent delta-9-tetrahydrocannabinol (THC) exposure fails to affect THC-induced place and taste conditioning in adult male rats.

    Science.gov (United States)

    Wakeford, Alison G P; Flax, Shaun M; Pomfrey, Rebecca L; Riley, Anthony L

    2016-01-01

    Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence.

    Science.gov (United States)

    Potenza, Marc N; Hong, Kwang-ik Adam; Lacadie, Cheryl M; Fulbright, Robert K; Tuit, Keri L; Sinha, Rajita

    2012-04-01

    Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

  18. Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

    Science.gov (United States)

    Robinson, Mike J F; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C

    2015-08-01

    Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever-conditioned stimulus; CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in 3 successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the CS+ lever versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also reported that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. (c) 2015 APA, all rights reserved).

  19. Low-temperature conditioning induces chilling tolerance in stored mango fruit.

    Science.gov (United States)

    Zhang, Zhengke; Zhu, Qinggang; Hu, Meijiao; Gao, Zhaoyin; An, Feng; Li, Min; Jiang, Yueming

    2017-03-15

    In this study, mango fruit were pre-treated with low-temperature conditioning (LTC) at 12°C for 24h, followed by refrigeration at 5°C for 25days before removal to ambient temperature (25°C) to investigate the effects and possible mechanisms of LTC on chilling injury (CI). The results showed that LTC effectively suppressed the development of CI in mango fruit, accelerated softening, and increased the soluble solids and proline content. Furthermore, LTC reduced electrolyte leakage, and levels of malondialdehyde, O 2 - and H 2 O 2 , maintaining membrane integrity. To reveal the molecular regulation of LTC on chilling tolerance in mango fruit, a C-repeat/dehydration-responsive element binding factor (CBF) gene, MiCBF1, was identified and its expression in response to LTC was examined using RT-qPCR. LTC resulted in a higher MiCBF1 expression. These findings suggest that LTC enhances chilling tolerance in mango fruit by inducing a series of physiological and molecular responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Characteristics and significance of D-tagatose-induced liver enlargement in rats: An interpretative review.

    Science.gov (United States)

    Bär, A

    1999-04-01

    This review addresses the issue of asymptomatic liver enlargement in rats. It was necessitated by the observation of significantly increased liver weights in rats fed diets with 10 to 20% D-tagatose, a potential new bulk sweetener, for between 28 and 90 days. Increases of liver size without accompanying histopathological changes or impairment of organ function have been observed in rats in response to the ingestion of various xenobiotic compounds (including some food additives), changes of dietary composition (e.g. , high doses of fructose and sucrose), metabolic aberrations (e.g., diabetes), as well as normal pregnancy and lactation. The underlying mechanism(s) are not yet understood in detail but peroxisome proliferation, microsomal enzyme induction, increased storage of glycogen or lipids, and hyperfunction due to an excessive workload are well-established causes of hepatomegaly in rats. In D-tagatose- and fructose-fed rats, a treatment-related increase of hepatic glycogen storage was identified as a likely cause of the liver enlargement. Dietary levels of 5% and about 15-20% were determined as no-effect levels (NOEL) for D-tagatose- and fructose-induced liver enlargement, respectively. At doses above the NOEL, D-tagatose is about four times more efficient than fructose in inducing liver enlargement. On the other hand, the estimated intake of D-tagatose from its intended uses in food is about four times lower than the actual fructose intake. Consequently, a similar safety margin would apply for both sugars. Considering the similarity of the liver effects in rats of fructose, a safe food ingredient, and D-tagatose, the absence of histopathological changes in rats fed a diet with 20% D-tagatose for 90 days, and the absence of adverse long-term consequences of glycogen-induced liver enlargement in rats, it is concluded that the observed liver enlargement in D-tagatose-fed rats has no relevance for the assessment of human safety of this substance. Copyright 1999

  1. Light-induced magnetoresistance in solution-processed planar hybrid devices measured under ambient conditions

    Directory of Open Access Journals (Sweden)

    Sreetama Banerjee

    2017-07-01

    Full Text Available We report light-induced negative organic magnetoresistance (OMAR measured in ambient atmosphere in solution-processed 6,13-bis(triisopropylsilylethynylpentacene (TIPS-pentacene planar hybrid devices with two different device architectures. Hybrid electronic devices with trench-isolated electrodes (HED-TIE having a channel length of ca. 100 nm fabricated in this work and, for comparison, commercially available pre-structured organic field-effect transistor (OFET substrates with a channel length of 20 µm were used. The magnitude of the photocurrent as well as the magnetoresistance was found to be higher for the HED-TIE devices because of the much smaller channel length of these devices compared to the OFETs. We attribute the observed light-induced negative magnetoresistance in TIPS-pentacene to the presence of electron–hole pairs under illumination as the magnetoresistive effect scales with the photocurrent. The magnetoresistance effect was found to diminish over time under ambient conditions compared to a freshly prepared sample. We propose that the much faster degradation of the magnetoresistance effect as compared to the photocurrent was due to the incorporation of water molecules in the TIPS-pentacene film.

  2. Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Brigitte Gonthier

    2012-01-01

    Full Text Available Aims. 3,5,4′-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10 μM slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100 μM enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol.

  3. Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

    Science.gov (United States)

    Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

    2017-06-01

    Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO 2 ). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O 2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO 2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO 2 . There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O 2 .

  4. Regulation of glucose transporter protein-1 and vascular endothelial growth factor by hypoxia inducible factor 1α under hypoxic conditions in Hep-2 human cells.

    Science.gov (United States)

    Xu, Ou; Li, Xiaoming; Qu, Yongtao; Liu, Shuang; An, Jie; Wang, Maoxin; Sun, Qingjia; Zhang, Wen; Lu, Xiuying; Pi, Lihong; Zhang, Min; Shen, Yupeng

    2012-12-01

    The present study evaluated the regulation of glucose transporter protein-1 (Glut-1) and vascular endothelial growth factor (VEGF) by hypoxia inducible factor 1α (HIF-1α) under hypoxic conditions in Hep-2 human cells to explore the feasibility of these three genes as tumor markers. Hep-2 cells were cultured under hypoxic and normoxic conditions for 6, 12, 24, 36 and 48 h. The proliferation of Hep-2 cells was evaluated using an MTT assay. The protein and mRNA expression levels of HIF-1α, Glut-1 and VEGF were detected using the S-P immunocytochemical method, western blotting and reverse transcription polymerase chain reaction (RT-PCR). The results revealed that the expression levels of HIF-1α, Glut-1 and VEGF protein in Hep-2 cells were significantly elevated under hypoxic conditions compared with those under normoxic conditions over 36 h. Under hypoxic conditions, mRNA levels of HIF-1α were stable, while mRNA levels of Glut-1 and VEGF changed over time. In conclusion, Glut-1 and VEGF were upregulated by HIF-1α under hypoxic conditions in a time-dependent manner in Hep-2 cells and their co-expression serves as a tumor marker.

  5. The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions.

    Science.gov (United States)

    Hessam, S; Sand, M; Skrygan, M; Bechara, Falk G

    2017-09-01

    Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

  6. Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues

    Science.gov (United States)

    Robinson, Mike J.F.; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C.

    2015-01-01

    Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine-sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in three successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the lever CS+ versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also report that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions together did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. PMID:26076340

  7. Significant clinical improvement in radiation-induced lumbosacral poly-radiculopathy by a treatment combining pentoxifylline, tocopherol, and clodronate (Pentoclo)

    Energy Technology Data Exchange (ETDEWEB)

    Delanian, S. [Hop St Louis, Serv Oncol Radiotherapie, APHP, F-75010 Paris, (France); Lefaix, J.L. [CEA-LARIA, CIRIL-GANIL, Caen, (France); Maisonobe, T. [Hop La Pitie Salpetriere, Federat Neurophysiol Clin, APHP, Paris, (France)

    2008-07-01

    Radiation-induced (RI) peripheral neuropathy is a rare and severe delayed complication of radiotherapy that is spontaneously irreversible, with no standard of treatment. We previously developed a successful antioxidant treatment in RI fibrosis and necrosis. Two patients with progressive worsening RI lumbosacral poly-radiculopathy experienced over several years a significant clinical improvement in their neurological sensorimotor symptoms with long-term pentoxifylline-tocopherol-clodronate treatment, and good safety. (authors)

  8. Elimination of remaining undifferentiated induced pluripotent stem cells in the process of human cardiac cell sheet fabrication using a methionine-free culture condition.

    Science.gov (United States)

    Matsuura, Katsuhisa; Kodama, Fumiko; Sugiyama, Kasumi; Shimizu, Tatsuya; Hagiwara, Nobuhisa; Okano, Teruo

    2015-03-01

    Cardiac tissue engineering is a promising method for regenerative medicine. Although we have developed human cardiac cell sheets by integration of cell sheet-based tissue engineering and scalable bioreactor culture, the risk of contamination by induced pluripotent stem (iPS) cells in cardiac cell sheets remains unresolved. In the present study, we established a novel culture method to fabricate human cardiac cell sheets with a decreased risk of iPS cell contamination while maintaining viabilities of iPS cell-derived cells, including cardiomyocytes and fibroblasts, using a methionine-free culture condition. When cultured in the methionine-free condition, human iPS cells did not survive without feeder cells and could not proliferate or form colonies on feeder cells or in coculture with cells for cardiac cell sheet fabrication. When iPS cell-derived cells after the cardiac differentiation were transiently cultured in the methionine-free condition, gene expression of OCT3/4 and NANOG was downregulated significantly compared with that in the standard culture condition. Furthermore, in fabricated cardiac cell sheets, spontaneous and synchronous beating was observed in the whole area while maintaining or upregulating the expression of various cardiac and extracellular matrix genes. These findings suggest that human iPS cells are methionine dependent and a methionine-free culture condition for cardiac cell sheet fabrication might reduce the risk of iPS cell contamination.

  9. Clinical significance of measurement of changes of serum TNF-α, IL-6 and IL-8 centent after treatment in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Wang Guiying

    2008-01-01

    Objective: To explore the clinical significance of changes of serum TNF-α, IL-6 and IL-8 levels in patients with pregnancy induced hypertension. Methods: Serum TNF-α, IL-6 and IL-8 levels were measured with RIA in 36 patients with pregnancy induced hypertension both before and after 2 weeks of treatment as well as in 35 controls. Results: Before treatment, the serum TNF-α, IL-6 and IL-8 levels were significantly higher in patients with PIH than those in the controls (P 0.05). Conclusion: The inflammatory cytokines such as TNF-α, IL-6 and IL-8 may play important roles in the pathogenesis of pregnancy induced hypertension. (authors)

  10. Coupled effects of director orientations and boundary conditions on light induced bending of monodomain nematic liquid crystalline polymer plates

    International Nuclear Information System (INIS)

    You, Yue; Ding, Shurong; Huo, Yongzhong; Xu, Changwei

    2012-01-01

    A photo-chromic liquid crystal polymers (LCPs) is a smart material for large light-activated variation or bending to transfer luminous energy into mechanical energy. We study the light induced behavior by modeling planar and homeotropic nematic network polymer plates. We effectively illustrate some reported experimental outcomes and theoretically predict some possible bending patterns. This paper constructs an understanding between the bending behaviors and interactions among the alignments, aspect ratios and boundary conditions, etc. Our work provides information on optimizing light induced bending in the process of micro-opto-mechanical system (MOMS) design. (paper)

  11. The significance of cladding material on the integrity of nuclear pressure vessels with cracks

    International Nuclear Information System (INIS)

    Sattari-Far, Iradj.

    1989-05-01

    The significance of the austenitic cladding layer is reviewed in this literature study. The cladding induced stresses are generally not considered when evaluating the severity of flaws in reactor pressure vessels. It has been shown that this emission may be misleading. The necessity to consider the cladding induced stresses is also emphasized in the latest edition of ASME XI. Contrary to what is commonly assumed, the austenitic cladding displays a charpy V transition region with a low ductility. The interface material (HAZ) is the most influenced region by irradiation, and a transition shift of over 100 degree C may be expected. Because of the significant difference in the thermal expansion coefficients of the cladding and the base metal, cladding induced stresses can be set up. Even after PWHT, residual stresses of yield magnitude remain in the cladding and the HAZ at ambient temperature. The cladding induced stresses are temperature dependent and decrease as the temperature increases. The cladding induced stresses have a significant influence on small defects near the inside surface of a pressure vessel. For semielliptical surface cracks, the maximum CTOD-value along the crack front is not found at the deepest point, but in the cladding/base metal interface, having a magnitude three times higher than the value in the deepest point. It implies that this type of crack would propagate along the clad/base material interface. At some point in time, the crack will reach a geometry which may cause such a severe condition at the deepest point that it will start to grow in the depth direction as well. The initiation and growth behaviour of such cracks need to be investigated to be able to assess the significance of cladding on the integrity of nuclear pressure vessels. (author) (50 figs., 33 refs.)

  12. Heat storage in forest biomass significantly improves energy balance closure particularly during stable conditions

    Science.gov (United States)

    Lindroth, A.; Mölder, M.; Lagergren, F.

    2009-08-01

    Temperature measurements in trunks and branches in a mature ca. 100 years-old mixed pine and spruce forest in central Sweden were used to estimate the heat storage in the tree biomass. The estimated heat flux in the sample trees and data on biomass distributions were used to scale up to stand level biomass heat fluxes. The rate of change of sensible and latent heat storage in the air layer below the level of the flux measurements was estimated from air temperature and humidity profile measurements and soil heat flux was estimated from heat flux plates and soil temperature measurements. The fluxes of sensible and latent heat from the forest were measured with an eddy covariance system in a tower. The analysis was made for a two-month period in summer of 1995. The tree biomass heat flux was the largest of the estimated storage components and varied between 40 and -35 W m-2 on summer days with nice weather. Averaged over two months the diurnal maximum of total heat storage was 45 W m-2 and the minimum was -35 W m-2. The soil heat flux and the sensible heat storage in air were out of phase with the biomass flux and they reached maximum values that were about 75% of the maximum of the tree biomass heat storage. The energy balance closure improved significantly when the total heat storage was added to the turbulent fluxes. The slope of a regression line with sum of fluxes and storage as independent and net radiation as dependent variable, increased from 0.86 to 0.95 for half-hourly data and the scatter was also reduced. The most significant finding was, however, that during nights with strongly stable conditions when the sensible heat flux dropped to nearly zero, the total storage matched the net radiation nearly perfectly. Another interesting result was that the mean energy imbalance started to increase when the Richardson number became more negative than ca. -0.1. In fact, the largest energy deficit occurred at maximum instability. Our conclusion is that eddy

  13. Plant cell death and cellular alterations induced by ozone: Key studies in Mediterranean conditions

    International Nuclear Information System (INIS)

    Faoro, Franco; Iriti, Marcello

    2009-01-01

    An account of histo-cytological and ultrastructural studies on ozone effect on crop and forest species in Italy is given, with emphasis on induced cell death and the underlying mechanisms. Cell death phenomena possibly due to ambient O 3 were recorded in crop and forest species. In contrast, visible O 3 effects on Mediterranean vegetation are often unclear. Microscopy is thus suggested as an effective tool to validate and evaluate O 3 injury to Mediterranean vegetation. A DAB-Evans blue staining was proposed to validate O 3 symptoms at the microscopic level and for a pre-visual diagnosis of O 3 injury. The method has been positively tested in some of the most important crop species, such as wheat, tomato, bean and onion and, with some restriction, in forest species, and it also allows one to gain some very useful insights into the mechanisms at the base of O 3 sensitivity or tolerance. - Ozone-induced cell death is a frequent phenomenon in Mediterranean conditions, not only in the most sensitive crops but also in forest species.

  14. Endomembrane Ca2+-AtPases play a significant role in virus-induced adaptation to oxidative stress

    DEFF Research Database (Denmark)

    Shabala, Sergey; Bækgaard, Lone; Shabala, Lana

    2011-01-01

    Although the role of Ca2+ influx channels in oxidative stress signaling and cross-tolerance in plants is well established, little is known about the role of active Ca2+ efflux systems in this process. In our recent paper,17 we reported Potato Virus X (PVX)-induced acquired resistance to oxidative...... in adaptive responses to oxidative stress by removing excessive Ca2+ from the cytosol, and that their functional expression is significantly altered in PVX-inoculated plants. These findings highlight the crucial role of Ca2+ efflux systems in acquired tolerance to oxidative stress and open up prospects...... stress in Nicotiana benthamiana and showed the critical role of plasma membrane Ca2+/H+ exchangers in this process. The current study continues this research. Using biochemical and electrophysiological approaches, we reveal that both endomembrane P2A and P2B Ca2+-ATPases play significant roles...

  15. Significance of settling model structures and parameter subsets in modelling WWTPs under wet-weather flow and filamentous bulking conditions

    DEFF Research Database (Denmark)

    Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen

    2014-01-01

    Current research focuses on predicting and mitigating the impacts of high hydraulic loadings on centralized wastewater treatment plants (WWTPs) under wet-weather conditions. The maximum permissible inflow to WWTPs depends not only on the settleability of activated sludge in secondary settling tanks...... (SSTs) but also on the hydraulic behaviour of SSTs. The present study investigates the impacts of ideal and non-ideal flow (dry and wet weather) and settling (good settling and bulking) boundary conditions on the sensitivity of WWTP model outputs to uncertainties intrinsic to the one-dimensional (1-D...... of settling parameters to the total variance of the key WWTP process outputs significantly depends on the influent flow and settling conditions. The magnitude of the impact is found to vary, depending on which type of 1-D SST model is used. Therefore, we identify and recommend potential parameter subsets...

  16. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Severe acute pancreatitis (SAP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS can lead to multiple organ dysfunction syndrome (MODS during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  17. Collision-induced stimulated photon echo generated at transition 0-1 on broad spectral line conditions

    Science.gov (United States)

    Rubtsova, N. N.; Gol'dort, V. G.; Ishchenko, V. N.; Khvorostov, E. B.; Kochubei, S. A.; Borisov, G. M.; Ledovskikh, D. V.; Reshetov, V. A.

    2018-04-01

    For the first time, the collision induced stimulated photon echo generated at transition 1S0 → 3 P1 of 174Yb (type 0-1) in the mixture of gases Yb  +  Xe was investigated in the presence of weak longitudinal magnetic field, with experimental parameters corresponding to broad spectral line conditions. Comparison of the experimental echo amplitude versus magnetic field strength dependence with the theoretical curve shows a very good agreement, giving rise to an improved estimate for the difference between alignment and orientation decay rates.

  18. Exercise training prevents the attenuation of anesthetic pre-conditioning-mediated cardioprotection in diet-induced obese rats.

    Science.gov (United States)

    Li, L; Meng, F; Li, N; Zhang, L; Wang, J; Wang, H; Li, D; Zhang, X; Dong, P; Chen, Y

    2015-01-01

    Obesity abolishes anesthetic pre-conditioning-induced cardioprotection due to impaired reactive oxygen species (ROS)-mediated adenosine monophosphate-activated protein kinase (AMPK) pathway, a consequence of increased basal myocardial oxidative stress. Exercise training has been shown to attenuate obesity-related oxidative stress. This study tests whether exercise training could normalize ROS-mediated AMPK pathway and prevent the attenuation of anesthetic pre-conditioning-induced cardioprotection in obesity. Male Sprague-Dawley rats were divided into lean rats fed with control diet and obese rats fed with high-fat diet. After 4 weeks of feeding, lean and obese rats were assigned to sedentary conditions or treadmill exercise for 8 weeks. There was no difference in infarct size between lean sedentary and obese sedentary rats after 25 min of myocardial ischemia followed by 120 min reperfusion. In lean rats, sevoflurane equally reduced infarct size in lean sedentary and lean exercise-trained rats. Molecular studies revealed that AMPK activity, endothelial nitric oxide synthase, and superoxide production measured at the end of ischemia in lean rats were increased in response to sevoflurane. In obese rats, sevoflurane increased the above molecular parameters and reduced infarct size in obese exercise-trained rats but not in obese sedentary rats. Additional study showed that obese exercise-trained rats had decreased basal oxidative stress than obese sedentary rats. The results indicate that exercise training can prevent the attenuation of anesthetic cardioprotection in obesity. Preventing the attenuation of this strategy may be associated with reduced basal oxidative stress and normalized ROS-mediated AMPK pathway, but the causal relationship remains to be determined. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

    Science.gov (United States)

    Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

    2018-05-21

    While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P 95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

  20. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines

    International Nuclear Information System (INIS)

    Mitov, Mihail I.; Harris, Jennifer W.; Alstott, Michael C.; Zaytseva, Yekaterina Y.; Evers, B. Mark; Butterfield, D. Allan

    2017-01-01

    Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograft cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.

  1. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Mitov, Mihail I., E-mail: m.mitov@uky.edu [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Harris, Jennifer W. [Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States); Alstott, Michael C.; Zaytseva, Yekaterina Y. [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Evers, B. Mark [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States); Butterfield, D. Allan [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Chemistry, University of Kentucky, Lexington, KY 40506 (United States)

    2017-05-15

    Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograft cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.

  2. Hypoxia inducible factor-1α-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells.

    Science.gov (United States)

    Li, Mingchuan; Wang, Yong Xing; Luo, Yong; Zhao, Jiahui; Li, Qing; Zhang, Jiao; Jiang, Yongguang

    2016-07-01

    Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death. Hypoxia is an environmental stimulus that plays an important role in the development and cancer progression especially for solid tumors. The key regulator under hypoxic conditions is stabilized hypoxia-inducible factor (HIF)-1α. In the present study, immune-fluorescent staining, siRNAs, qRT-PC, immunoblotting, cell migration and invasion assays were carried out to test typical epithelial to mesenchymal transition under hypoxia and the key regulators of this process in PC3, a human prostate cancer cell line. Our data demonstrated that hypoxia induces diverse molecular, phenotypic and functional changes in prostate cancer cells that are consistent with EMT. We also showed that a cell signal factor such as HIF-1α, which might be stabilized under hypoxic environment, is involved in EMT and cancer cell invasive potency. The induced hypoxia could be blocked by HIF-1α gene silencing and reoxygenation of EMT in prostate cancer cells, hypoxia partially reversed accompanied by a process of mesenchymal-epithelial reverting transition (MErT). EMT might be induced by activation of HIF-1α-dependent cell signaling in hypoxic prostate cancer cells.

  3. Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells

    International Nuclear Information System (INIS)

    Machiguchi, Toshihiko; Nakamura, Tatsuo

    2013-01-01

    Highlights: •We have attempted in vivo nephron generation using conditioned media. •Vascular and tubular cells do cross-talks on cell proliferation and tubular changes. •Tubular cells suppress these changes in mesenchymal stem cells. •Tubular cells differentiate mesenchymal stem cells into tubular cells. •Nephrons can be created from implanted tubular cells or mesenchymal stem cells. -- Abstract: There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues

  4. A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

    Directory of Open Access Journals (Sweden)

    Schoen CJ

    2016-09-01

    Full Text Available Cynthia J Schoen,1,* Jacob N Ablin,2,* Eric Ichesco,1 Rupal J Bhavsar,3 Laura Kochlefl,1 Richard E Harris,1 Daniel J Clauw,1 Richard H Gracely,4 Steven E Harte1 1Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA; 2Institute of Rheumatology, Tel Aviv Suorasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Neurology, University of Pennsylvania, Philadelphia, PA, 4Department of Endodontics, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA *These authors contributed equally to this work Introduction: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM. The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM patients using thumb pressure as both a test and conditioning stimulus.Methods: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.Results: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively. In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect P-values >0

  5. Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference.

    Science.gov (United States)

    Jerlhag, Elisabet; Egecioglu, Emil; Dickson, Suzanne L; Engel, Jörgen A

    2010-09-01

    Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine. We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist. Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

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

    Science.gov (United States)

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

    2014-06-22

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

  7. Effects of gas conditions on ASH induced agglomeration

    DEFF Research Database (Denmark)

    Ma, T.; Fan, C. G.; Hao, L. F.

    2016-01-01

    Agglomeration is a serious problem for gasification and combustion of biomass in fluidized bed. Agglomeration characteristics may be affected by gas condition, but the literature is quite vague in this regard. This study focuses on the effects of gasification and combustion condition...... on agglomeration tendency with two types of biomass ash, including rice straw and wheat straw ash. The agglomerates are analyzed by SEM-EDS for morphology and elemental composition. Defluidization temperature (Td) in those two types of gas conditions is quite different. Tdin gasification condition is much lower...

  8. The metabolic response of Candida albicans to farnesol under hyphae-inducing conditions.

    Science.gov (United States)

    Han, Ting-Li; Cannon, Richard D; Villas-Bôas, Silas G

    2012-12-01

    Farnesol is a quorum-sensing molecule (QSM) produced, and sensed, by the polymorphic fungus, Candida albicans. This cell-to-cell communication molecule is known to suppress the hyphal formation of C. albicans at high cell density. Despite many studies investigating the signalling mechanisms by which QSMs influence the morphogenesis of C. albicans, the downstream metabolic effect of these signalling pathways in response to farnesol-mediated morphogenesis remains obscure. Here, we have used metabolomics to investigate the metabolic response of C. albicans upon exposure to farnesol under hyphae-inducing conditions. We have found a general up-regulation of central carbon metabolic pathways when hyphal formation was suppressed by farnesol evidenced by a considerably larger number of central carbon metabolic intermediates detected under this condition at an overall lower intracellular level. By combining the metabolic profiles from farnesol-exposed cells with previous metabolomics data for C. albicans undergoing morphogenesis, we have identified several metabolic pathways that are likely to be associated with the morphogenetic process of C. albicans, as well as metabolic pathways such as those involved in lipid metabolism that appeared to be specifically affected by farnesol. Therefore, our results provide important new insights into the metabolic role of farnesol in C. albicans metabolism. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  9. β-Adrenergic Receptor Mediation of Stress-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Roles for β1 and β2 Adrenergic Receptors

    Science.gov (United States)

    Vranjkovic, Oliver; Hang, Shona; Baker, David A.

    2012-01-01

    Stress can trigger the relapse of drug use in recovering cocaine addicts and reinstatement in rodent models through mechanisms that may involve norepinephrine release and β-adrenergic receptor activation. The present study examined the role of β-adrenergic receptor subtypes in the stressor-induced reinstatement of extinguished cocaine-induced (15 mg/kg i.p.) conditioned place preference in mice. Forced swim (6 min at 22°C) stress or activation of central noradrenergic neurotransmission by administration of the selective α2 adrenergic receptor antagonist 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL-44,408) (10 mg/kg i.p.) induced reinstatement in wild-type, but not β- adrenergic receptor-deficient Adrb1/Adrb2 double-knockout, mice. In contrast, cocaine administration (15 mg/kg i.p.) resulted in reinstatement in both wild-type and β-adrenergic receptor knockout mice. Stress-induced reinstatement probably involved β2 adrenergic receptors. The β2 adrenergic receptor antagonist -(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI-118,551) (1 or 2 mg/kg i.p.) blocked reinstatement by forced swim or BRL-44,408, whereas administration of the nonselective β-adrenergic receptor agonist isoproterenol (2 or 4 mg/kg i.p.) or the β2 adrenergic receptor-selective agonist clenbuterol (2 or 4 mg/kg i.p.) induced reinstatement. Forced swim-induced, but not BRL-44,408-induced, reinstatement was also blocked by a high (20 mg/kg) but not low (10 mg/kg) dose of the β1 adrenergic receptor antagonist betaxolol, and isoproterenol-induced reinstatement was blocked by pretreatment with either ICI-118,551 or betaxolol, suggesting a potential cooperative role for β1 and β2 adrenergic receptors in stress-induced reinstatement. Overall, these findings suggest that targeting β-adrenergic receptors may represent a promising pharmacotherapeutic strategy for preventing drug relapse, particularly in cocaine addicts whose drug use is stress

  10. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

    Science.gov (United States)

    Lee, Dae-Hee; Lee, Yong J

    2008-10-01

    Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

  11. Statistical significant changes in ground thermal conditions of alpine Austria during the last decade

    Science.gov (United States)

    Kellerer-Pirklbauer, Andreas

    2016-04-01

    Longer data series (e.g. >10 a) of ground temperatures in alpine regions are helpful to improve the understanding regarding the effects of present climate change on distribution and thermal characteristics of seasonal frost- and permafrost-affected areas. Beginning in 2004 - and more intensively since 2006 - a permafrost and seasonal frost monitoring network was established in Central and Eastern Austria by the University of Graz. This network consists of c.60 ground temperature (surface and near-surface) monitoring sites which are located at 1922-3002 m a.s.l., at latitude 46°55'-47°22'N and at longitude 12°44'-14°41'E. These data allow conclusions about general ground thermal conditions, potential permafrost occurrence, trend during the observation period, and regional pattern of changes. Calculations and analyses of several different temperature-related parameters were accomplished. At an annual scale a region-wide statistical significant warming during the observation period was revealed by e.g. an increase in mean annual temperature values (mean, maximum) or the significant lowering of the surface frost number (F+). At a seasonal scale no significant trend of any temperature-related parameter was in most cases revealed for spring (MAM) and autumn (SON). Winter (DJF) shows only a weak warming. In contrast, the summer (JJA) season reveals in general a significant warming as confirmed by several different temperature-related parameters such as e.g. mean seasonal temperature, number of thawing degree days, number of freezing degree days, or days without night frost. On a monthly basis August shows the statistically most robust and strongest warming of all months, although regional differences occur. Despite the fact that the general ground temperature warming during the last decade is confirmed by the field data in the study region, complications in trend analyses arise by temperature anomalies (e.g. warm winter 2006/07) or substantial variations in the winter

  12. Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells.

    Science.gov (United States)

    Gu, Hanna; Song, Mina; Boonanantanasarn, Kanitsak; Baek, Kyunghwa; Woo, Kyung Mi; Ryoo, Hyun-Mo; Baek, Jeong-Hwa

    2018-01-09

    Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation. However, the molecular mechanisms by which hyperglycemia affects osteogenic differentiation are yet to be clarified. This study aimed to investigate whether the aberrant increase in protein O -linked-β- N -acetylglucosamine glycosylation ( O -GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia. To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2). Excessive protein O -GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N -acetylglucosamine concentrations or by O -GlcNAc transferase (OGT) overexpression. The effect of O -GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation. Cell treatment with high glucose, glucosamine or N -acetylglucosamine increased O -GlcNAcylation of Runx2 and the total levels of O -GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase. These inhibitory effects were rescued by lowering protein O -GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β- N -acetylglucosaminidase. Our findings suggest that excessive protein O -GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.

  13. Autophagy‑mediated adaptation of hepatocellular carcinoma cells to hypoxia‑mimicking conditions constitutes an attractive therapeutic target.

    Science.gov (United States)

    Owada, Satoshi; Endo, Hitoshi; Shida, Yukari; Okada, Chisa; Ito, Kanako; Nezu, Takahiro; Tatemichi, Masayuki

    2018-04-01

    Hepatocellular carcinoma has extremely poor prognosis. In cancerous liver tissues, aberrant proliferation of cancer cells leads to the creation of an area where an immature vascular network is formed. Since oxygen is supplied to cancer tissues through the bloodstream, a part of the tumor is exposed to hypoxic conditions. As hypoxia is known to severely reduce the effectiveness of existing anticancer agents, novel valid therapeutic targets must be identified for the treatment of hepatocellular carcinoma. Generally, autophagy has been reported to play an important role in the adaptation of cancer cells to hypoxia. However, the exact role and significance of this process vary depending on the cancer type, requiring detailed analysis in individual primary tumors and cell lines. In the present study, we examined autophagy induced by cobalt chloride, a hypoxia‑mimicking agent, in hepatocellular carcinoma cells with the aim to evaluate the validity of this process as a potential therapeutic target. We observed that treatment with cobalt chloride induced autophagy, including the intracellular quality control mechanism, in an AMPK‑dependent manner. Furthermore, treatment with autophagy inhibitors (bafilomycin and LY294002) resulted in significant, highly‑selective cytotoxicity and apoptosis activation under hypoxia‑mimicking conditions. The knockdown of AMPK also revealed significant cytotoxicity in hypoxia‑mimicking conditions. These results clearly demonstrated that autophagy, especially mitophagy, was induced by the AMPK pathway when hepatocellular carcinoma cells were subjected to hypoxic conditions and played an important role in the adaptation of these cells to such conditions. Thus, autophagy may constitute an attractive therapeutic target for the treatment of hepatocellular carcinoma.

  14. Laser-Induced Reductive Sintering of Nickel Oxide Nanoparticles under Ambient Conditions

    KAUST Repository

    Paeng, Dongwoo; Lee, Daeho; Yeo, Junyeob; Yoo, Jae-Hyuck; Allen, Frances I.; Kim, Eunpa; So, Hongyun; Park, Hee K.; Minor, Andrew M.; Grigoropoulos, Costas P.

    2015-01-01

    © 2015 American Chemical Society. This work is concerned with the kinetics of laser-induced reductive sintering of nonstoichiometric crystalline nickel oxide (NiO) nanoparticles (NPs) under ambient conditions. The mechanism of photophysical reductive sintering upon irradiation using a 514.5 nm continuous-wave (CW) laser on NiO NP thin films has been studied through modulating the laser power density and illumination time. Protons produced due to high-temperature decomposition of the solvent present in the NiO NP ink, oxygen vacancies in the NiO NPs, and electronic excitation in the NiO NPs by laser irradiation all affect the early stage of the reductive sintering process. Once NiO NPs are reduced by laser irradiation to Ni, they begin to coalesce, forming a conducting material. In situ optical and electrical measurements during the reductive sintering process take advantage of the distinct differences between the oxide and the metallic phases to monitor the transient evolution of the process. We observe four regimes: oxidation, reduction, sintering, and reoxidation. A characteristic time scale is assigned to each regime.

  15. Laser-Induced Reductive Sintering of Nickel Oxide Nanoparticles under Ambient Conditions

    KAUST Repository

    Paeng, Dongwoo

    2015-03-19

    © 2015 American Chemical Society. This work is concerned with the kinetics of laser-induced reductive sintering of nonstoichiometric crystalline nickel oxide (NiO) nanoparticles (NPs) under ambient conditions. The mechanism of photophysical reductive sintering upon irradiation using a 514.5 nm continuous-wave (CW) laser on NiO NP thin films has been studied through modulating the laser power density and illumination time. Protons produced due to high-temperature decomposition of the solvent present in the NiO NP ink, oxygen vacancies in the NiO NPs, and electronic excitation in the NiO NPs by laser irradiation all affect the early stage of the reductive sintering process. Once NiO NPs are reduced by laser irradiation to Ni, they begin to coalesce, forming a conducting material. In situ optical and electrical measurements during the reductive sintering process take advantage of the distinct differences between the oxide and the metallic phases to monitor the transient evolution of the process. We observe four regimes: oxidation, reduction, sintering, and reoxidation. A characteristic time scale is assigned to each regime.

  16. Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

    Science.gov (United States)

    Zhang, Yue; Pop, Ioana L; Carlson, Noel G; Kishore, Bellamkonda K

    2012-01-01

    Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li-added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD.

  17. Increased heme synthesis in yeast induces a metabolic switch from fermentation to respiration even under conditions of glucose repression.

    Science.gov (United States)

    Zhang, Tiantian; Bu, Pengli; Zeng, Joey; Vancura, Ales

    2017-10-13

    Regulation of mitochondrial biogenesis and respiration is a complex process that involves several signaling pathways and transcription factors as well as communication between the nuclear and mitochondrial genomes. Under aerobic conditions, the budding yeast Saccharomyces cerevisiae metabolizes glucose predominantly by glycolysis and fermentation. We have recently shown that altered chromatin structure in yeast induces respiration by a mechanism that requires transport and metabolism of pyruvate in mitochondria. However, how pyruvate controls the transcriptional responses underlying the metabolic switch from fermentation to respiration is unknown. Here, we report that this pyruvate effect involves heme. We found that heme induces transcription of HAP4 , the transcriptional activation subunit of the Hap2/3/4/5p complex, required for growth on nonfermentable carbon sources, in a Hap1p- and Hap2/3/4/5p-dependent manner. Increasing cellular heme levels by inactivating ROX1 , which encodes a repressor of many hypoxic genes, or by overexpressing HEM3 or HEM12 induced respiration and elevated ATP levels. Increased heme synthesis, even under conditions of glucose repression, activated Hap1p and the Hap2/3/4/5p complex and induced transcription of HAP4 and genes required for the tricarboxylic acid (TCA) cycle, electron transport chain, and oxidative phosphorylation, leading to a switch from fermentation to respiration. Conversely, inhibiting metabolic flux into the TCA cycle reduced cellular heme levels and HAP4 transcription. Together, our results indicate that the glucose-mediated repression of respiration in budding yeast is at least partly due to the low cellular heme level. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Methanolic extract of Morinda citrifolia L. (noni unripe fruit attenuates ethanol-induced conditioned place preferences in mice

    Directory of Open Access Journals (Sweden)

    Yasmin Khan

    2016-09-01

    Full Text Available Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC, on compulsive ethanol-seeking behaviour using the mouse conditioned place preference (CPP test. CPP was established by injections of ethanol (2g/kg, i.p. in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM, on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3 and 5g/kg and ACAM (300 mg/kg 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction, during which the treatment groups received MMC (1, 3 and 5g/kg, p.o. or ACAM (300 mg/kg, p.o.. Finally, a priming injection of a low dose of ethanol (0.4g/kg, i.p. in the home cage (Reinstatement was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5g/kg, p.o and ACAM (300 mg/kg, p.o. significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

  19. Propagation of a probe pulse inside a Bose–Einstein condensate under conditions of electromagnetically induced transparency

    International Nuclear Information System (INIS)

    Barberis-Blostein, Pablo; Aguilar-Loreto, Omar

    2015-01-01

    We obtain a partial differential equation for a pulse travelling inside a Bose–Einstein condensate under conditions of electromagnetically induced transparency. The equation is valid for a weak probe pulse. We solve the equation for the case of a three-level BEC in Λ configuration with one of its ground state spatial profiles initially constant. The solution characterizes, in detail, the effect that the evolution of the condensate wave function has on pulse propagation, including the process of stopping and releasing it. (invited comment)

  20. Optimizing pentacene thin-film transistor performance: Temperature and surface condition induced layer growth modification.

    Science.gov (United States)

    Lassnig, R; Hollerer, M; Striedinger, B; Fian, A; Stadlober, B; Winkler, A

    2015-11-01

    In this work we present in situ electrical and surface analytical, as well as ex situ atomic force microscopy (AFM) studies on temperature and surface condition induced pentacene layer growth modifications, leading to the selection of optimized deposition conditions and entailing performance improvements. We prepared p ++ -silicon/silicon dioxide bottom-gate, gold bottom-contact transistor samples and evaluated the pentacene layer growth for three different surface conditions (sputtered, sputtered + carbon and unsputtered + carbon) at sample temperatures during deposition of 200 K, 300 K and 350 K. The AFM investigations focused on the gold contacts, the silicon dioxide channel region and the highly critical transition area. Evaluations of coverage dependent saturation mobilities, threshold voltages and corresponding AFM analysis were able to confirm that the first 3-4 full monolayers contribute to the majority of charge transport within the channel region. At high temperatures and on sputtered surfaces uniform layer formation in the contact-channel transition area is limited by dewetting, leading to the formation of trenches and the partial development of double layer islands within the channel region instead of full wetting layers. By combining the advantages of an initial high temperature deposition (well-ordered islands in the channel) and a subsequent low temperature deposition (continuous film formation for low contact resistance) we were able to prepare very thin (8 ML) pentacene transistors of comparably high mobility.

  1. Pavlovian conditioning between co-administered drugs: elicitation of an apomorphine-induced antiparkinsonian response by scopolamine.

    Science.gov (United States)

    Carey, R J

    1991-01-01

    Sprague-Dawley rats with unilateral 6-OHDA substantia nigra lesions were given combined scopolamine (0.5 mg/kg IP) and apomorphine (0.05 mg/kg SC) treatments. In this animal model, scopolamine, when administered separately, induces ipsilateral rotation and apomorphine, contralateral rotation. When these drugs are co-administered at 0.5 mg/kg and 0.05 mg/kg dose levels, respectively, animals rotate in the contralateral direction, creating the opportunity for the stimulus effect of scopolamine to become associated with the response effect of apomorphine. In tests with scopolamine (0.5 mg/kg), animals that previously had scopolamine and apomorphine co-administered rotated contralaterally in the test chamber, thereby behaving as if they had received apomorphine. Thus, scopolamine exhibited a functionally acquired conditioned stimulus (CS) property by eliciting the apomorphine response of contralateral rotation as a conditioned response. This acquired CS property was extinguished with separate scopolamine trials and reacquired following one scopolamine-apomorphine co-administration trial.

  2. Drug induced neutropenia manifesting as oral ulcerations

    Directory of Open Access Journals (Sweden)

    Rachna Kaul

    2009-01-01

    Full Text Available As dental practitioners, we often come across oral ulcerations of varied etiology. Among all the causes of oral ulcers, those due to neutropenia are significant. Neutropenia can occur in many systemic conditions and also in patients on long-term therapy of certain drugs like phenytoin. The diagnosis of neutropenia in time leads to early recognition of the cause of this fatal condition. Here, we report a case of a 50-year-old female patient who developed oral ulcerations secondary to phenytoin-induced neutropenia. Early diagnosis of the condition led to discontinuation of the offending drug and significant improvement in her blood picture and also prevented her from falling prey to many other systemic infections that neutropenia can cause.

  3. Multiple loci condition seed transmission of soybean mosaic virus (SMV) and SMV-induced seed coat mottling in soybean.

    Science.gov (United States)

    Domier, Leslie L; Hobbs, Houston A; McCoppin, Nancy K; Bowen, Charles R; Steinlage, Todd A; Chang, Sungyul; Wang, Yi; Hartman, Glen L

    2011-06-01

    Infection of soybean plants with Soybean mosaic virus (SMV), which is transmitted by aphids and through seed, can cause significant reductions in seed production and quality. Because seedborne infections are the primary sources of inoculum for SMV infections in North America, host-plant resistance to seed transmission can limit the pool of plants that can serve as sources of inoculum. To examine the inheritance of SMV seed transmission in soybean, crosses were made between plant introductions (PIs) with high (PI88799), moderate (PI60279), and low (PI548391) rates of transmission of SMV through seed. In four F(2) populations, SMV seed transmission segregated as if conditioned by two or more genes. Consequently, a recombinant inbred line population was derived from a cross between PIs 88799 and 548391 and evaluated for segregation of SMV seed transmission, seed coat mottling, and simple sequence repeat markers. Chromosomal regions on linkage groups C1 and C2 were significantly associated with both transmission of isolate SMV 413 through seed and SMV-induced seed coat mottling, and explained ≈42.8 and 46.4% of the variability in these two traits, respectively. Chromosomal regions associated with seed transmission and seed coat mottling contained homologues of Arabidopsis genes DCL3 and RDR6, which encode enzymes involved in RNA-mediated transcriptional and posttranscriptional gene silencing.

  4. Silicification-induced cell aggregation for the sustainable production of H2 under aerobic conditions.

    Science.gov (United States)

    Xiong, Wei; Zhao, Xiaohong; Zhu, Genxing; Shao, Changyu; Li, Yaling; Ma, Weimin; Xu, Xurong; Tang, Ruikang

    2015-10-05

    Photobiological hydrogen production is of great importance because of its promise for generating clean renewable energy. In nature, green algae cannot produce hydrogen as a result of the extreme sensitivity of hydrogenase to oxygen. However, we find that silicification-induced green algae aggregates can achieve sustainable photobiological hydrogen production even under natural aerobic conditions. The core-shell structure of the green algae aggregates creates a balance between photosynthetic electron generation and hydrogenase activity, thus allowing the production of hydrogen. This finding provides a viable pathway for the solar-driven splitting of water into hydrogen and oxygen to develop green energy alternatives by using rationally designed cell-material complexes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Optimal conditions for taking spectra of coffee beans plasma spectroscopy induced by laser (LIBS)

    International Nuclear Information System (INIS)

    Diaz Guerrero, A. M.; Flores Reyes; Ponce Cabrera, L. V.

    2016-01-01

    Coffee beans, arabica and robusta, from Mexico (Chiapas and Veracruz), Colombia, Kenya and Sumatra were analyzed by Laser-induced breakdown spectroscopy (LIBS). The time delay and pulse energy were varied in order to find the optimal conditions for taking spectra in coffee beans; finding that the increased visibility of the peaks and the lowest electronic background is observed with 1 s and 450 mJ. Spectra were taken in different regions of grain area to confirm its homogeneous composition. It was found that the intensity of the signal Ca is much higher than that of K in African coffee, lower in the coffee of America, and much lower in the coffee from Asia. (Author)

  6. A psychophysical study of endogenous analgesia: the role of the conditioning pain in the induction and magnitude of conditioned pain modulation.

    Science.gov (United States)

    Nir, Rony-Reuven; Granovsky, Yelena; Yarnitsky, David; Sprecher, Elliot; Granot, Michal

    2011-05-01

    Endogenous analgesia (EA) can be examined experimentally using a conditioned pain modulation (CPM) paradigm. While noxious conditioning stimulation intensities (CSIs) are mainly used, it has not been fully investigated in the same experimental design whether the experienced conditioning pain level affects CPM responses. The principal goal of the present study was to characterize CPM induction and magnitudes evoked by various conditioning pain levels. Furthermore, we explored associations between conditioning pain reports and CPM responses across various CSIs. Thirty healthy, young, right-handed males were tested with a parallel CPM paradigm. Three different CSIs (hand water-immersion) induced mild, moderate and intense pain levels, rated 12.41 ± 7.85, 31.57 ± 9.56 and 58.1 ± 11.43, respectively (0-100 numerical pain scale) (P < 0.0001). Contact-heat 'test-stimulus' levels were compared before and during conditioning. Within the group, (i) CPM was induced only by the moderate and intense CSIs (Ps ≤ 0.001); (ii) no difference was demonstrated between the magnitudes of these CPM responses. Regression analysis revealed that CPM induction was independent of the perceived conditioning pain level, but associated with the absolute CSI (P < 0.0001). Conditioning pain levels were correlated across all CSIs, as were CPM magnitudes (Ps ≤ 0.01). We conclude that among males, (i) once a CPM response is evoked by a required conditioning pain experience, its magnitude is not further affected by increasing conditioning pain and (ii) CPM magnitudes are inter-correlated, but unrelated to conditioning pain reports. These observations may suggest that CPM responses represent an intrinsic element of an individual's EA processes, which are not significantly affected by the experienced conditioning pain. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  7. Pavlovian conditioning of nausea and vomiting.

    Science.gov (United States)

    Stockhorst, Ursula; Steingrueber, Hans-Joachim; Enck, Paul; Klosterhalfen, Sibylle

    2006-10-30

    Cancer patients undergoing cytotoxic drug treatment often experience side-effects, the most distressing being nausea and vomiting. Despite antiemetic drugs, 25-30% of the chemotherapy patients report these side-effects when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea and anticipatory vomiting. The present paper summarizes the evidence that anticipatory vomiting is acquired by Pavlovian conditioning, and, consequently, may be alleviated by conditioning techniques. To explore the mechanisms that induce and alleviate conditioned nausea and vomiting further, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea was demonstrated. Cortisol and tumor-necrosis factor-alpha were elevated as endocrine and immunological correlates of nausea. Data in the rotation-induced motion sickness model indicated that gender is an important moderator variable to be considered in further studies. The paper concludes with a review of applications of the demonstrated conditioning principles as interventions to ameliorate distressing anticipatory nausea or anticipatory vomiting in cancer patients undergoing chemotherapy.

  8. Evaluative conditioning induces changes in sound valence

    Directory of Open Access Journals (Sweden)

    Anna C. Bolders

    2012-04-01

    Full Text Available Evaluative Conditioning (EC has hardly been tested in the auditory domain, but it is a potentially valuable research tool. In Experiment 1 we investigated whether the affective evaluation of short environmental sounds can be changed using affective words as unconditioned stimuli (US. Congruence effects on an affective priming task (APT for conditioned sounds demonstrated successful EC. Subjective ratings for sounds paired with negative words changed accordingly. In Experiment 2 we investigated whether the acquired valence remains stable after repeated presentation of the conditioned sound without the US or whether extinction occurs. The acquired affective value remained present, albeit weaker, even after 40 extinction trials. These results warrant the use of EC to study processing of short environmental sounds with acquired valence, even if this requires repeated stimulus presentations. This paves the way for studying processing of affective environmental sounds while effectively controlling low level-stimulus properties.

  9. Pavlovian conditioning of psychomotor stimulant-induced behaviours: has convenience led us astray?

    Science.gov (United States)

    Martin-Iverson, M.T.; Fawcett, S.L.

    1996-01-01

    In order to classically condition the behavioural effects of psychomotor stimulants within a test context, rats were treated for 10 days with (+)-amphetamine (1.5mg/kg), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 30µg/kg) or vehicle prior to a 1h placement into a test box. Conditioned behavioural effects were then measured in the previously drug-paired context after a vehicle injection (drug-free test day). Each rat was videotaped for the 1h test box exposure on days 1, 4, 7 and 10 of the drug conditioning trials, and on the drug-free test day. Eleven of 28 behaviours that were scored for frequency, duration and mean bout duration (bout length) were significantly influenced by at least one of the two drugs. Amphetamine predominantly increased bout lengths while PHNO predominantly increased bout frequency. Only two measures that were influenced by the drugs exhibited clear increases over controls in a manner consistent with a classical conditioning interpretation. Behavioural sensitization clearly occurred to some of the effects of amphetamine and PHNO, but these were not the same effects as those increased on the non-drug day testing for classical conditioning. Most behavioural effects of amphetamine and PHNO are not classically conditioned, and behavioural sensitization to these drugs, while perhaps context-specific, is not due to classical conditioning. Automated measures of behaviours have provided misleading evidence concerning the similarity among behavioural effects of stimulants, sensitization and effects of exposure to an environment previously paired with stimulants. Analysis of transitions between behaviours does not support the view that stimulants increase switching or response competition, or that behavioural reorganization is responsible for sensitization. Rather, it is suggested that stimulants selectively facilitate current stimulus-guided behaviours.

  10. Evaluations of two-phase natural circulation flow induced in the reactor vessel annular gap under ERVC conditions

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Kwang Soon, E-mail: tomo@kaeri.re.kr [Korea Atomic Energy Research Institute, 1045 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cheung, Fan-Bill [The Pennsylvania State University, University Park, PA 16802 (United States); Park, Rae Joon; Kim, Sang Baik [Korea Atomic Energy Research Institute, 1045 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)

    2012-12-15

    Highlights: Black-Right-Pointing-Pointer Two-phase natural circulation flow induced in insulation gap was investigated. Black-Right-Pointing-Pointer Half-scaled non-heating experiments were performed to evaluate flow behavior. Black-Right-Pointing-Pointer The loop-integrated momentum equation was formulated and solved asymptotically. Black-Right-Pointing-Pointer First-order approximate solution was obtained and agreed with experimental data. - Abstract: The process of two-phase natural circulation flow induced in the annular gap between the reactor vessel and the insulation under external reactor vessel cooling conditions was investigated experimentally and analytically in this study. HERMES-HALF experiments were performed to observe and quantify the induced two-phase natural circulation flow in the annular gap. A half-scaled non-heating experimental facility was designed by utilizing the results of a scaling analysis to simulate the APR1400 reactor and its insulation system. The behavior of the boiling-induced two-phase natural circulation flow in the annular gap was observed, and the liquid mass flow rates driven by the natural circulation loop and the void fraction distribution were measured. Direct flow visualization revealed that choking would occur under certain flow conditions in the minimum gap region near the shear keys. Specifically, large recirculation flows were observed in the minimum gap region for large air injection rates and small outlet areas. Under such conditions, the injected air could not pass through the minimum gap region, resulting in the occurrence of choking near the minimum gap with a periodical air back flow being generated. Therefore, a design modification of the minimum gap region needs to be done to facilitate steam venting and to prevent choking from occurring. To complement the HERMES-HALF experimental effort, an analytical study of the dependence of the induced natural circulation mass flow rate on the inlet area and the

  11. Significance of dipyridamole-induced transient dilation of the left ventricle during thallium-201 scintigraphy in suspected coronary artery disease

    International Nuclear Information System (INIS)

    Chouraqui, P.; Rodrigues, E.A.; Berman, D.S.; Maddahi, J.

    1990-01-01

    The occurrence and significance of transient dilation of the left ventricle during dipyridamole stress-redistribution thallium-201 scintigraphy was studied in 73 patients who underwent both dipyridamole thallium-201 study and coronary angiography. Transient dilation ratio was calculated from planar anterior images by dividing the computer-derived left ventricular area on the initial image by that of the 4-hour image. In 11 patients with normal coronary arteriograms or less than 50% coronary stenosis, the transient dilation ratio was 0.98 +/- 0.046. An abnormal transient dilation ratio was defined as greater than or equal to 1.12, representing greater than or equal to 3 standard deviations above the mean normal value. When the 15 patients with an abnormal ratio were compared with the 58 with a normal ratio, the former group had a significantly higher frequency of 3 critical (greater than or equal to 90%) coronary stenoses (33 vs 5%), higher prevalence of collaterals (67 vs 24%), more extensive myocardial reversible defects by planar (71 vs 10%) or by single-photon emission computed tomography (87.5 vs 35%) imaging and a higher incidence of dipyridamole-induced anginal chest pain (53 vs 22%). No significant difference between the 2 groups was noted with respect to age, gender, prior myocardial infarction, single or double critical coronary stenosis, dipyridamole-induced ischemic electrocardiographic response and increased lung uptake. An abnormal transient dilation ratio of greater than or equal to 1.12 was a specific marker of multivessel (87%) or 3-vessel (85%) critical coronary artery disease

  12. Heterogeneity of equilibrium molten globule state of cytochrome c induced by weak salt denaturants under physiological condition.

    Directory of Open Access Journals (Sweden)

    Hamidur Rahaman

    Full Text Available While many proteins are recognized to undergo folding via intermediate(s, the heterogeneity of equilibrium folding intermediate(s along the folding pathway is less understood. In our present study, FTIR spectroscopy, far- and near-UV circular dichroism (CD, ANS and tryptophan fluorescence, near IR absorbance spectroscopy and dynamic light scattering (DLS were used to study the structural and thermodynamic characteristics of the native (N, denatured (D and intermediate state (X of goat cytochorme c (cyt-c induced by weak salt denaturants (LiBr, LiCl and LiClO4 at pH 6.0 and 25°C. The LiBr-induced denaturation of cyt-c measured by Soret absorption (Δε400 and CD ([θ]409, is a three-step process, N ↔ X ↔ D. It is observed that the X state obtained along the denaturation pathway of cyt-c possesses common structural and thermodynamic characteristics of the molten globule (MG state. The MG state of cyt-c induced by LiBr is compared for its structural and thermodynamic parameters with those found in other solvent conditions such as LiCl, LiClO4 and acidic pH. Our observations suggest: (1 that the LiBr-induced MG state of cyt-c retains the native Met80-Fe(III axial bond and Trp59-propionate interactions; (2 that LiBr-induced MG state of cyt-c is more compact retaining the hydrophobic interactions in comparison to the MG states induced by LiCl, LiClO4 and 0.5 M NaCl at pH 2.0; and (3 that there exists heterogeneity of equilibrium intermediates along the unfolding pathway of cyt-c as highly ordered (X1, classical (X2 and disordered (X3, i.e., D ↔ X3 ↔ X2 ↔ X1 ↔ N.

  13. Studies on clinical significance of exercise-induced ST-segment depression at non-infarct-related leads in the patients with prior myocardial infarction using the stress scintigraphy

    International Nuclear Information System (INIS)

    Ohkubo, Toshitaka

    1988-01-01

    Stress Tl-201 myocardial imaging and stress radionuclide ventriculography were performed in a total of 67 patients with prior myocardial infarction (MI) to assess the clinical significance of exercise induced ST-segment depression at non-infarct-related leads on ECG during the chronic stage. The patients consisted of 12 with inferior MI with single vessel disease (SVD) that showed no precordial ST-segment depression; 7 with inferior MI with SVD accompanied by precordial ST-segment depression; 13 with inferior MI with multivessel disease (MVD); 20 with anterior MI with SVD that showed no inferior ST-segment depression; 4 with anterior MI with SVD accompanied by inferior ST-segment depression; and 11 with anterior MI with MVD. In cases of SVD, the incidence of ST-segment depression at non-infarct-related leads was higher for inferior MI (36.8%) than anterior MI (16.7%). Myocardial imaging revealed large infarct and infarct extending into the inferoseptal wall of the left ventricle (LV) in cases of exercise induced precordial ST-segment depression; and infarct extending into the lateral wall of LV in cases of exercise induced inferior ST-segment depression. In detecting MVD, stress Tl-201 myocardial imaging was superior to exercise electrocardiography and stress radionuclide ventriculography, but this was not statistically significant. Prognostic value of error rate for detecting MVD was significantly improved with a discriminant analysis. Exercise induced ST-segment depression on ECG should be of clinical significance in reflecting myocardial ischemia around an infarcted area. (Namekawa, K)

  14. Visually induced analgesia during massage treatment in chronic back pain patients.

    Science.gov (United States)

    Löffler, A; Trojan, J; Zieglgänsberger, W; Diers, M

    2017-11-01

    Previous findings suggest that watching sites of experimental and chronic pain can exert an analgesic effect. Our present study investigates whether watching one's back during massage increases the analgesic effect of this treatment in chronic back pain patients. Twenty patients with chronic back pain were treated with a conventional massage therapy. During this treatment, patients received a real-time video feedback of their own back. Watching a neutral object, a video of another person of the same sex being massaged, a picture of the own back, and keeping one's eyes closed were used as controls. These conditions were presented in randomized order on five separate days. All conditions yielded significant decreases in habitual pain intensity. The effect of real-time video feedback of the own back on massage treatment was the strongest and differed significantly from the effect of watching a neutral object, but not from the other control conditions, which may have induced slight effects of their own. Repeated real-time video feedback may be useful during massage treatment of chronic pain. This study shows that inducing visual induced analgesia during massage treatment can be helpful in alleviating chronic pain. © 2017 European Pain Federation - EFIC®.

  15. Direct-to-consumer prescription drug advertising, 1989-1998. A content analysis of conditions, targets, inducements, and appeals.

    Science.gov (United States)

    Bell, R A; Kravitz, R L; Wilkes, M S

    2000-04-01

    We conducted a content analysis of consumer-targeted prescription drug advertisements to explore trends in prevalence, shifts in the medical conditions for which drugs are promoted, reliance on financial and nonmonetary inducements, and appeals used to attract public interest. We collected the drug advertisements appearing in 18 consumer magazines from 1989 through 1998. Two judges independently coded each advertisement and placed it in a category pertaining to the target audience, use of inducements, and product benefits (mean kappa=0.93). We employed descriptive statistics, cross-tabulations, and curve estimation procedures. A total of 320 distinct advertisements were identified, representing 101 brands and 14 medical conditions. New advertisement and brand introductions increased dramatically during this decade. Advertisements for drugs used for dermatologic, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and obstetric/gynecologic conditions were most common. Almost all of the advertisements were aimed at the potential user of the drug, not third-party intermediaries such as parents and spouses. Although most advertisements were gender-neutral, women were more likely to be exclusively targeted. One eighth of the advertisements offered a monetary incentive (eg, a rebate or money-back guarantee), and one third made an offer of additional information in printed or audio/video form. The most common appeals used were effectiveness, symptom control, innovativeness, and convenience. Consumer-directed prescription drug advertising has increased dramatically during the past decade. The pharmaceutical industry is turning to this type of advertising to generate interest in its products. Our data may be useful to physicians who want to stay abreast of the treatments that are being directly marketed to their patients.

  16. Osmosis-induced water uptake by Eurobitum bituminized radioactive waste and pressure development in constant volume conditions

    International Nuclear Information System (INIS)

    Mariën, A.; Mokni, N.; Valcke, E.; Olivella, S.; Smets, S.; Li, X.

    2013-01-01

    Highlights: ► The water uptake by Eurobitum is studied to judge the safety of geological disposal. ► High pressures of up to 20 MPa are measured in constant volume water uptake tests. ► The morphology of leached Eurobitum samples is studied with μCT and ESEM. ► The observations are reproduced by an existing CHM formulation for Eurobitum. - Abstract: The chemo-hydro-mechanical (CHM) interaction between swelling Eurobitum radioactive bituminized waste (BW) and Boom Clay is investigated to assess the feasibility of geological disposal for the long-term management of this waste. These so-called compatibility studies include laboratory water uptake tests at Belgian Nuclear Research Center SCK-CEN, and the development of a coupled CHM formulation for Eurobitum by the International Center for Numerical Methods and Engineering (CIMNE, Polytechnical University of Cataluña, Spain). In the water uptake tests, the osmosis-induced swelling, pressure increase and NaNO 3 leaching of small cylindrical BW samples (diameter 38 mm, height 10 mm) is studied under constant total stress conditions and nearly constant volume conditions; the actual geological disposal conditions should be intermediate between these extremes. Two nearly constant volume tests were stopped after 1036 and 1555 days to characterize the morphology of the hydrated BW samples and to visualize the hydrated part with microfocus X-ray Computer Tomography (μCT) and Environmental Scanning Electron Microscopy (ESEM). In parallel, a coupled CHM formulation is developed that describes chemically and hydraulically coupled flow processes in porous materials with salt crystals, and that incorporates a porosity dependent membrane efficiency, permeability and diffusivity. When Eurobitum BW is hydrated in (nearly) constant volume conditions, the osmosis-induced water uptake results in an increasing pressure to values that can be (in theory) as high as 42.8 MPa, being the osmotic pressure of a saturated NaNO 3

  17. Optimal conditions of LDR to protect the kidney from diabetes

    Science.gov (United States)

    Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

    2014-01-01

    Aims We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day via suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Main methods Type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic mice received whole body X-irradiation at dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th week of the study. Key findings Diabetes induced renal dysfunction, shown by the decreased creatinine and increased microalbumin in urinary. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best preventive effect on the kidney of diabetic mice. Significance Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. PMID:24631139

  18. Keto analogues and amino acids supplementation induces a decrease of white blood cell counts and a reduction of muscle damage during intense exercise under thermoneutral conditions.

    Science.gov (United States)

    Lima, R C P; Camerino, S R A S; França, T C L; Rodrigues, D S A; Gouveia, M G S; Ximenes-da-Silva, A; Bassini, A; Prado, E S; Cameron, L C

    2017-04-19

    This study evaluated the acute effect of keto analogue and amino acid (AA-KAAA) supplementation on both white blood cell counts and the established biomarkers of muscle damage during exercise under thermoneutral conditions. Sixteen male cyclists received a ketogenic diet for two days and were divided into two equal groups: a group taking AA-KAAA (KA) or a control group (PL). The athletes performed a two hour cycling session followed by a maximum incremental test until voluntary exhaustion (VExh). Blood samples were obtained at rest and during exercise for further hematological and biochemical analyses. Exercise-induced ammonemia increased in the PL group at VExh (75%) but remained unchanged in the KA group. Both groups exhibited a significant increase in leukocyte and neutrophil counts of ∼85% (∼13 × 10 9 L -1 ), but the shape of the lymphocytes and the eosinophil counts suggest that AA-KAAA supplementation helps prevent lymphocytosis. AA-KAAA supplementation induced a decrease in creatine kinase and aspartate aminotransferase levels at VExh while showing a significant decrease in lactate dehydrogenase at 120 min. We found that AA-KAAA supplementation decreases both the lymphocyte count response in blood and the established biomarkers of muscle damage after intense exercise under a low heat stress environment.

  19. Schizophrenia affects speech-induced functional connectivity of the superior temporal gyrus under cocktail-party listening conditions.

    Science.gov (United States)

    Li, Juanhua; Wu, Chao; Zheng, Yingjun; Li, Ruikeng; Li, Xuanzi; She, Shenglin; Wu, Haibo; Peng, Hongjun; Ning, Yuping; Li, Liang

    2017-09-17

    The superior temporal gyrus (STG) is involved in speech recognition against informational masking under cocktail-party-listening conditions. Compared to healthy listeners, people with schizophrenia perform worse in speech recognition under informational speech-on-speech masking conditions. It is not clear whether the schizophrenia-related vulnerability to informational masking is associated with certain changes in FC of the STG with some critical brain regions. Using sparse-sampling fMRI design, this study investigated the differences between people with schizophrenia and healthy controls in FC of the STG for target-speech listening against informational speech-on-speech masking, when a listening condition with either perceived spatial separation (PSS, with a spatial release of informational masking) or perceived spatial co-location (PSC, without the spatial release) between target speech and masking speech was introduced. The results showed that in healthy participants, but not participants with schizophrenia, the contrast of either the PSS or PSC condition against the masker-only condition induced an enhancement of functional connectivity (FC) of the STG with the left superior parietal lobule and the right precuneus. Compared to healthy participants, participants with schizophrenia showed declined FC of the STG with the bilateral precuneus, right SPL, and right supplementary motor area. Thus, FC of the STG with the parietal areas is normally involved in speech listening against informational masking under either the PSS or PSC conditions, and declined FC of the STG in people with schizophrenia with the parietal areas may be associated with the increased vulnerability to informational masking. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Maximiliano Rapanelli

    Full Text Available Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC and the hippocampus (HIPP during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and

  1. Periodontal response to orthodontic tooth movement in diabetes-induced rats with or without periodontal disease.

    Science.gov (United States)

    Ferreira, Camila Lopes; da Rocha, Vinicius Clemente; da Silva Ursi, Weber José; De Marco, Andrea Carvalho; Santamaria, Milton; Santamaria, Mauro Pedrine; Jardini, Maria Aparecida Neves

    2018-03-01

    Systemic conditions can influence orthodontic tooth movement. This study evaluates histologic periodontal responses to orthodontic tooth movement in diabetes-induced rats with or without periodontal disease. Forty Wistar rats were divided according their systemic condition (SC) into diabetic (D) and non-diabetic (ND) groups. Each group was subdivided into control (C), orthodontic tooth movement (OM), ligature-induced periodontitis (P) and ligature-induced periodontitis with orthodontic movement (P+OM) groups. Diabetes mellitus (DM) was induced with alloxan monohydrate, and after 30 days, the P group received a cotton ligature around their first lower molar crown. An orthodontic device was placed in OM and P+OM groups for 7 days, and the animals were then euthanized. Differences in OM between D and ND groups were not significant (6.87± 3.55 mm and 6.81 ± 3.28 mm, respectively), but intragroup analysis revealed statistically significant differences between the P+OM groups for both SCs. Bone loss was greater in the D group (0.16 ± 0.07 mm 2 ) than in the ND group (0.10 ± 0.03 mm 2 ). In intragroup analysis of the D condition, the P+OM group differed statistically from the other groups, while in the ND condition, the P+OM group was different from the C and OM groups. There was a statistically significant difference in bone density between D and ND conditions (18.03 ± 8.09% and 22.53 ± 7.72%) in the C, P, and P+OM groups. DM has deleterious effects on bone density and bone loss in the furcation region. These effects are maximized when associated with ligature-induced periodontitis with orthodontic movement. © 2018 American Academy of Periodontology.

  2. [Stress-induced cellular adaptive mutagenesis].

    Science.gov (United States)

    Zhu, Linjiang; Li, Qi

    2014-04-01

    The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

  3. Radiographic changes following radiotherapy in the patients with lung cancer. Is the irradiated area of the mediastinum in the simulation film a significant factor?

    International Nuclear Information System (INIS)

    Yamazaki, H.; Tang, J.T.; Inoue, T.; Teshima, T.; Ohtani, M.; Itou, M.; Takeuchi, E.; Inoue, T.

    1995-01-01

    To evaluate the significance of the irradiated area of the mediastinum in the simulation film for radiation induced lung injury. A total of 208 patients with primary lung cancer treated with radiation therapy were analyzed for incidence of radiation induced lung injury. Lung injury was defined as the appearance of an abnormal shadow on the chest radiograph. CT images were used to differentiate recurrence or other conditions. Age, sex, irradition dose, irradiated lung area, T and N factors of the tumor, irradiated mediastinum area, performance status of patients, location of irradiated fields and use of chemotherapy were analyzed with Cox's multivariate regression model. The cumulative rate of radiation induced lung injury at 12 months was 85%. Significant factor of radiation induced lung injury was irradiated area of the mediastinum (p=0.03). Irradiated area of the lung (p=0.18, n.s.), total tumor dose (p=0.1, n.s.), use of chemotherapy (p=0.08, n.s.) and location of irradiated field (p=0.08, n.s.) may also have an effect on radiation induced lung injury. The irradiated area of the mediastinum is one of the significant factors in radiation induced lung injury. (orig.) [de

  4. Clinical significance of determination of changes of serum TNF-α levels, peripheral B lymphocyte count and T lymphocyte subsets distribution pattern in patients with pregnancy induced hypertension syndrome

    International Nuclear Information System (INIS)

    Zhao Wenjuan

    2006-01-01

    Objective: To explore the changes of serum TNF-α levels, peripheral B cell count and T subsets distribution pattern in patients with pregnancy induced hypertension syndrome. Methods: Serum TNF-α levels (with RIA), peripheral B cell count as well as T subsets (with monoclonal technique) were examined in 34 patients with pregnancy induced hypertension syndrome and 35 controls. Results: The serum TNF-α levels and B lymphocytes count were significantly higher than those in controls (P 3 , CD 4 , CD4/CD8 ratio were significantly lower than those in controls (P<0.01). Conclusion: Pregnancy induced hY- pertension syndrome is a kind of autoimmune diseases with abnormal immunoregulation. (authors)

  5. Gut Microbiota Analysis in Rats with Methamphetamine-Induced Conditioned Place Preference

    Directory of Open Access Journals (Sweden)

    Tingting Ning

    2017-08-01

    Full Text Available Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP were analyzed through 16S rRNA gene sequencing. The fecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the fecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

  6. Significance of hair-dye base-induced sensory irritation.

    Science.gov (United States)

    Fujita, F; Azuma, T; Tajiri, M; Okamoto, H; Sano, M; Tominaga, M

    2010-06-01

    Oxidation hair-dyes, which are the principal hair-dyes, sometimes induce painful sensory irritation of the scalp caused by the combination of highly reactive substances, such as hydrogen peroxide and alkali agents. Although many cases of severe facial and scalp dermatitis have been reported following the use of hair-dyes, sensory irritation caused by contact of the hair-dye with the skin has not been reported clearly. In this study, we used a self-assessment questionnaire to measure the sensory irritation in various regions of the body caused by two model hair-dye bases that contained different amounts of alkali agents without dyes. Moreover, the occipital region was found as an alternative region of the scalp to test for sensory irritation of the hair-dye bases. We used this region to evaluate the relationship of sensitivity with skin properties, such as trans-epidermal water loss (TEWL), stratum corneum water content, sebum amount, surface temperature, current perception threshold (CPT), catalase activities in tape-stripped skin and sensory irritation score with the model hair-dye bases. The hair-dye sensitive group showed higher TEWL, a lower sebum amount, a lower surface temperature and higher catalase activity than the insensitive group, and was similar to that of damaged skin. These results suggest that sensory irritation caused by hair-dye could occur easily on the damaged dry scalp, as that caused by skin cosmetics reported previously.

  7. A Role for Matrix Metalloproteinases in Nicotine-Induced Conditioned Place Preference and Relapse in Adolescent Female Rats

    Directory of Open Access Journals (Sweden)

    Reka Natarajan

    2013-01-01

    Full Text Available Reconfiguration of extracellular matrix proteins appears to be necessary for the synaptic plasticity that underlies memory consolidation. The primary candidates involved in controlling this process are a family of endopeptidases called matrix metalloproteinases (MMPs; however, the potential role of MMPs in nicotine addiction-related memories has not been adequately tested. Present results indicate transient changes in hippocampal MMP-2, -3, and -9 expression following context dependent learning of nicotine-induced conditioned place preference (CPP. Members of a CPP procedural control group also indicated similar MMP changes, suggesting that memory activation occurred in these animals as well. However, hippocampal MMP-9 expression was differentially elevated in members of the nicotine-induced CPP group on days 4 and 5 of training. Inhibition of MMPs using a broad spectrum MMP inhibitor (FN439 during nicotine-induced CPP training blocked the acquisition of CPP. Elevations in hippocampal and prefrontal cortex MMP-3 expression—but not MMP-2 and -9—accompanied reactivation of a previously learned drug related memory. Decreases in the actin regulatory cytoskeletal protein cortactin were measured in the HIP and PFC during the initial two days of acquisition of CPP; however, no changes were seen following re-exposure to the drug related environment. These results suggest that MMP-9 may be involved in facilitating the intracellular and extracellular events required for the synaptic plasticity underlying the acquisition of nicotine-induced CPP. Furthermore, MMP-3 appears to be important during re-exposure to the drug associated environment. However, rats introduced into the CPP apparatus and given injections of vehicle rather than nicotine during training also revealed a pattern of MMP expression similar to nicotine-induced CPP animals.

  8. Significance of oxidized low-density lipoprotein in body fluids as a marker related to diseased conditions.

    Science.gov (United States)

    Itabe, Hiroyuki; Kato, Rina; Sasabe, Naoko; Obama, Takashi; Yamamoto, Matsuo

    2018-03-06

    Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of oxLDL and LDL rather than oxLDL concentration alone has been focused attention. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in circulatory system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Evaluation of intubating conditions after rocuronium bromide in adults induced with propofol or thiopentone sodium

    Directory of Open Access Journals (Sweden)

    Moazzam Md Shahnawaz

    2011-01-01

    Full Text Available Aim: The aims of present study were to compare the propofol and rocuronium with thiopentone and rocuronium in terms of clinically satisfactory intubating conditions and to co-relate intubating conditions with degree of paralysis in adductor pollicis muscle using train of four ratio (TOFR. The intubating conditions were evaluated after rocuronium bromide 0.6 mg kg−1 at 60 s. Materials and Methods : 60 patients of ASA grades I-II of either sex, age 18-50 years, undergoing various elective surgical procedures were randomly divided into two groups, propofol rocuronium (PR group and thiopentone rocuronium (TR group of 30 patients in each. In the PR group, patients received propofol 2.5 mg kg−1 and rocuronium 0.6 mg kg−1 ; in TR group, patients received thiopentone 5 mg kg−1 and rocuronium 0.6 mg kg−1 . In all patients the intubating conditions were evaluated by the observer at 60 s. TOFR was measured at the time of intubation by an assistant. Results : In the PR group the number of the patients placed in intubating conditions grades I, II, III and IV were 40%, 36.67%, 13.33% and 10% and their mean TOFR were 31.8±17.9%, 61.8±;14.6%, 61.7±27.9%, and 78.3±5.7% respectively. While in theTR group the number of patients placed in intubating condition grade I, II, and III were 60%, 26.67%, and 13.33% and their mean TOFR , 41.2±28.3%, 68.0±10.9% and 78.7±6.8%, respectively. There was no patient in grade lV in theTR group. Conclusion : The clinical intubating conditions and degree of paralysis of adductor pollicis muscle after rocuronium 0.6 mg kg−1 at 60 s in adults induced with propofol or thiopentone sodium are comparable.

  10. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems.

    Science.gov (United States)

    Li, Xiang; Huang, Mengbing; Yang, Lihua; Guo, Ningning; Yang, Xiaoyan; Zhang, Zhimin; Bai, Ming; Ge, Lu; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

    2018-01-01

    Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABA B R were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABA B R in the VTA and NAc.

  11. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2018-05-01

    Full Text Available Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1 is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA and γ-aminobutyric acid (GABA systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA and nucleus accumbens (NAc in wild-type (WT mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc.

  12. Effect of Different Ground Scenarios on Flow Structure of a Rotor At Hover Condition

    Science.gov (United States)

    Kocak, Goktug; Nalbantoglu, Volkan; Yavuz, Mehmet Metin

    2017-11-01

    The ground effect of a scaled model rotor at hover condition was investigated experimentally in a confined environment. Different ground effect scenarios including full, partial, and inclined conditions, compared to out of ground condition, were characterized qualitatively and quantitatively using laser illuminated smoke visualization and Laser Doppler Anemometry measurements. The results indicate that the presence of the ground affects the flow regime near the blade tip by changing the spatial extent and the path of the vortex core. After the impingement of the wake to the ground, highly unsteady and turbulent wake is observed. Both the mean and the root mean square of the induced velocity increase toward the blade tip. In line with this, the spectral power of the dominant frequency in the velocity fluctuations significantly increases toward the blade tip. All these observations are witnessed in all ground effect conditions tested in the present study. Considering the inclined ground effect in particular, it is observed that the mean induced velocities of the high side (mountain) are higher compared to the velocities of the low side (valley) in contrast to the general trend observed in the present study where the ground effect reduces the induced velocity.

  13. Social participation and healthy ageing: a neglected, significant protective factor for chronic non communicable conditions

    Directory of Open Access Journals (Sweden)

    Joseph Jennifer

    2011-10-01

    Full Text Available Abstract Background Low and middle income countries are ageing at a much faster rate than richer countries, especially in Asia. This is happening at a time of globalisation, migration, urbanisation, and smaller families. Older people make significant contributions to their families and communities, but this is often undermined by chronic disease and preventable disability. Social participation can help to protect against morbidity and mortality. We argue that social participation deserves much greater attention as a protective factor, and that older people can play a useful role in the prevention and management of chronic conditions. We present, as an example, a low-cost, sustainable strategy that has increased social participation among elders in Sri Lanka. Discussion Current international policy initiatives to address the increasing prevalence of non-communicable chronic diseases are focused on cardiovascular disease, diabetes, respiratory disease and cancers, responsible for much premature mortality. Interventions to modify their shared risk factors of high salt and fat diets, inactivity, smoking and alcohol use are advocated. But older people also suffer chronic conditions that primarily affect quality of life, and have a wider range of risk factors. There is strong epidemiological and physiological evidence that social isolation, in particular, is as important a risk factor for chronic diseases as the 'lifestyle' risk factors, yet it is currently neglected. There are useful experiences of inexpensive and sustainable strategies to improve social participation among older people in low and lower middle income countries. Our experience with forming Elders' Clubs with retired tea estate workers in Sri Lanka suggests many benefits, including social support and participation, inter-generational contact, a collective voice, and facilitated access to health promotion activities, and to health care and social welfare services. Summary Policies to

  14. Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning.

    Science.gov (United States)

    Chia, Chester; Otto, Tim

    2013-11-01

    Mounting evidence suggests that long-lasting, protein synthesis-dependent changes in synaptic strength accompany both the initial acquisition and subsequent recall of specific memories. Within brain areas thought to be important for learning and memory, including the hippocampus, learning-related plasticity is likely mediated in part by NMDA receptor activation and experience-dependent changes in gene expression. In the present study, we examined the role of activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition, recall, and reconsolidation of memory in a trace fear conditioning paradigm. First, we show that the expression of Arc protein in ventral hippocampus (VH) is dramatically enhanced by memory recall 24h after the acquisition of trace fear conditioning, and that both memory recall and the associated recall-induced enhancement of Arc expression are blocked by pre-training administration of 2-amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect on memory recall, it significantly reduced both Arc protein expression and freezing behavior during subsequent testing sessions. Collectively, these results suggest that Arc/Arg3.1 protein plays an important functional role in both the initial acquisition of hippocampal-dependent memory and the reconsolidation of these memories after recall. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Bacillus spp. from rainforest soil promote plant growth under limited nitrogen conditions.

    Science.gov (United States)

    Huang, X-F; Zhou, D; Guo, J; Manter, D K; Reardon, K F; Vivanco, J M

    2015-03-01

    The aim of this study was to evaluate effects of PGPR (plant growth-promoting rhizobacteria) isolated from rainforest soil on different plants under limited nitrogen conditions. Bacterial isolates from a Peruvian rainforest soil were screened for plant growth-promoting effects on Arabidopsis (Col-0). Four selected isolates including one Bacillus subtilis, two B. atrophaeus and one B. pumilus significantly promoted growth of Zea mays L. and Solanum lycopersicum under greenhouse conditions. Moreover, the PGPRs significantly promoted growth of S. lycopersicum in both low and nitrogen-amended soil conditions. These PGPR strains were further studied to obtain insights into possible mechanisms of plant growth promotion. Volatile chemicals from those isolates promoted Arabidopsis growth, and the expression of genes related to IAA production was induced in the Arabidopsis plants treated with PGPRs. Further, selected PGPR strains triggered induced systemic resistance (ISR) against Pseudomonas syringae pv tomato DC3000 in Arabidopsis. PGPR strains isolated from the rainforest soil promoted the plant growth of Arabidopsis, corn and tomato. New PGPR that have wider adaptability to different crops, soils and environmental conditions are needed to decrease our reliance on agricultural amendments derived from fossil-based fuels. The PGPRs isolated from a nonagricultural site constitute new plant growth-promoting strains that could be developed for agricultural uses. © 2014 The Society for Applied Microbiology.

  16. The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-11-01

    Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Analysis on the formation condition of the algae-induced odorous black water agglomerate.

    Science.gov (United States)

    Wang, Guofang; Li, Xianning; Fang, Yang; Huang, Rui

    2014-12-01

    The algae-induced odorous black water agglomerate (OBWA) is a phenomenon in which water turns black and emits odorous gas. It is an ecological and environmental problem that has occurred several times in Taihu, a large eutrophic shallow lake in China. In this study, the collected eutrophic water with different algae densities was used to simulate OBWA. The results revealed that the massive accumulation and death of algae was the substrate source for OBWA. When the algae density reached 1.0 × 10(8) cells/L in the static and dark condition, at a constant high temperature (30 ± 2 °C), OBWA happened. There was a time difference between the water stinking and blackening with the stinking first. When the oxidation-reduction potential (ORP) value was between -250 and -50 mV, Dimethyl trisulfide (DMTS), the main contributor to the water stinking at the initial stage, and other odorous organics were produced. Water blackening was closely related to the increases of sulfide and dissolved Fe(2+) concentration. When the ORP value was between -350 and -300 mV, heavy metal containing sulfides such as FeS formed. Therefore, the condition when the water ORP value decreased to about -300 mV was considered the precursor for OBWA formation.

  18. Chemically induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oshimura, M.; Barrett, J.C.

    1986-01-01

    A literature review with over 200 references examines the growing body of evidence from human and animal cancer cytogenetics that aneuploidy is an important chromosome change in carcinogenesis. Evidence from in vitro cell transformation studies supports the idea that aneuploidy has a direct effect on the conversion of a normal cell to a preneoplastic or malignant cell. Induction of an aneuploid state in a preneoplastic or neoplastic cell could have any of the following four biological effects: a change in gene dosage, a change in gene balance, expression of a recessive mutation, or a change in genetic instability (which could secondarily lead to neoplasia). There are a number of possible mechanisms by which chemicals might induce aneuploidy, including effects on microtubules, damage to essential elements for chromosome function reduction in chromosome condensation or pairing, induction of chromosome interchanges, unresolved recombination structures, increased chromosome stickiness, damage to centrioles, impairment of chromosome alignment ionic alterations during mitosis, damage to the nuclear membrane, and a physical disruption of chromosome segregation. Therefore, a number of different targets exist for chemically induced aneuploidy.

  19. Temporal pore pressure induced stress changes during injection and depletion

    Science.gov (United States)

    Müller, Birgit; Heidbach, Oliver; Schilling, Frank; Fuchs, Karl; Röckel, Thomas

    2016-04-01

    Induced seismicity is observed during injection of fluids in oil, gas or geothermal wells as a rather immediate response close to the injection wells due to the often high-rate pressurization. It was recognized even earlier in connection with more moderate rate injection of fluid waste on a longer time frame but higher induced event magnitudes. Today, injection-related induced seismicity significantly increased the number of events with M>3 in the Mid U.S. However, induced seismicity is also observed during production of fluids and gas, even years after the onset of production. E.g. in the Groningen gas field production was required to be reduced due to the increase in felt and damaging seismicity after more than 50 years of exploitation of that field. Thus, injection and production induced seismicity can cause severe impact in terms of hazard but also on economic measures. In order to understand the different onset times of induced seismicity we built a generic model to quantify the role of poro-elasticity processes with special emphasis on the factors time, regional crustal stress conditions and fault parameters for three case studies (injection into a low permeable crystalline rock, hydrothermal circulation and production of fluids). With this approach we consider the spatial and temporal variation of reservoir stress paths, the "early" injection-related induced events during stimulation and the "late" production induced ones. Furthermore, in dependence of the undisturbed in situ stress field conditions the stress tensor can change significantly due to injection and long-term production with changes of the tectonic stress regime in which previously not critically stressed faults could turn to be optimally oriented for fault reactivation.

  20. Fear conditioning induced by interpersonal conflicts in healthy individuals.

    Science.gov (United States)

    Tada, Mitsuhiro; Uchida, Hiroyuki; Maeda, Takaki; Konishi, Mika; Umeda, Satoshi; Terasawa, Yuri; Nakajima, Shinichiro; Mimura, Masaru; Miyazaki, Tomoyuki; Takahashi, Takuya

    2015-01-01

    Psychophysiological markers have been focused to investigate the psychopathology of psychiatric disorders and personality subtypes. In order to understand neurobiological mechanisms underlying these conditions, fear-conditioning model has been widely used. However, simple aversive stimuli are too simplistic to understand mechanisms because most patients with psychiatric disorders are affected by social stressors. The objective of this study was to test the feasibility of a newly-designed conditioning experiment using a stimulus to cause interpersonal conflicts and examine associations between personality traits and response to that stimulus. Twenty-nine healthy individuals underwent the fear conditioning and extinction experiments in response to three types of stimuli: a simple aversive sound, disgusting pictures, and pictures of an actors' face with unpleasant verbal messages that were designed to cause interpersonal conflicts. Conditioned response was quantified by the skin conductance response (SCR). Correlations between the SCR changes, and personality traits measured by the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised NEO Personality Inventory were explored. The interpersonal conflict stimulus resulted in successful conditioning, which was subsequently extinguished, in a similar manner as the other two stimuli. Moreover, a greater degree of conditioned response to the interpersonal conflict stimulus correlated with a higher ZAN-BPD total score. Fear conditioning and extinction can be successfully achieved, using interpersonal conflicts as a stimulus. Given that conditioned fear caused by the interpersonal conflicts is likely associated with borderline personality traits, this paradigm could contribute to further understanding of underlying mechanisms of interpersonal fear implicated in borderline personality disorder.

  1. Fear Conditioning Induced by Interpersonal Conflicts in Healthy Individuals

    Science.gov (United States)

    Tada, Mitsuhiro; Uchida, Hiroyuki; Maeda, Takaki; Konishi, Mika; Umeda, Satoshi; Terasawa, Yuri; Nakajima, Shinichiro; Mimura, Masaru; Miyazaki, Tomoyuki; Takahashi, Takuya

    2015-01-01

    Psychophysiological markers have been focused to investigate the psychopathology of psychiatric disorders and personality subtypes. In order to understand neurobiological mechanisms underlying these conditions, fear-conditioning model has been widely used. However, simple aversive stimuli are too simplistic to understand mechanisms because most patients with psychiatric disorders are affected by social stressors. The objective of this study was to test the feasibility of a newly-designed conditioning experiment using a stimulus to cause interpersonal conflicts and examine associations between personality traits and response to that stimulus. Twenty-nine healthy individuals underwent the fear conditioning and extinction experiments in response to three types of stimuli: a simple aversive sound, disgusting pictures, and pictures of an actors’ face with unpleasant verbal messages that were designed to cause interpersonal conflicts. Conditioned response was quantified by the skin conductance response (SCR). Correlations between the SCR changes, and personality traits measured by the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised NEO Personality Inventory were explored. The interpersonal conflict stimulus resulted in successful conditioning, which was subsequently extinguished, in a similar manner as the other two stimuli. Moreover, a greater degree of conditioned response to the interpersonal conflict stimulus correlated with a higher ZAN-BPD total score. Fear conditioning and extinction can be successfully achieved, using interpersonal conflicts as a stimulus. Given that conditioned fear caused by the interpersonal conflicts is likely associated with borderline personality traits, this paradigm could contribute to further understanding of underlying mechanisms of interpersonal fear implicated in borderline personality disorder. PMID:25978817

  2. iTRAQ proteomic analysis of the hippocampus in a rat model of nicotine-induced conditioned place preference.

    Science.gov (United States)

    Zhu, Beibei; Li, Xiangyu; Chen, Huan; Wang, Hongjuan; Zhu, Xinchao; Hou, Hongwei; Hu, Qingyuan

    2017-05-13

    Repeated exposures to nicotine are known to result in persistent changes in proteins expression in addiction-related brain regions, such as the striatum, nucleus accumbens and prefrontal cortex, but the changes induced in the protein content of the hippocampus remain poorly studied. This study established a rat model of nicotine-induced conditioned place preference (CPP), and screened for proteins that were differentially expressed in the hippocampus of these rats using isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The nicotine-induced CPP was established by subcutaneously injecting rats with 0.2 mg/kg nicotine. Relative to the control (saline) group, the nicotine group showed 0.67- and 1.5-fold changes in 117 and 10 hippocampal proteins, respectively. These differentially expressed proteins are mainly involved in calcium-mediated signaling, neurotransmitter transport, GABAergic synapse function, long-term synaptic potentiation and nervous system development. Furthermore, RT-PCR was used to confirmed the results of the proteomic analysis. Our findings identify several proteins and cellular signaling pathways potentially involved in the molecular mechanisms in the hippocampus that underlie nicotine addiction. These results provide insights into the mechanisms of nicotine treatment in hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

    Science.gov (United States)

    Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

    2011-11-20

    Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Selective Breeding under Saline Stressed Conditions of Canola Mutations Induced by Gamma Rays

    International Nuclear Information System (INIS)

    Amer, I.M.; Moustafa, H.A.M.; Mansour, M.F.

    2009-01-01

    Mutation breeding program has been initiated for inducing canola mutations tolerance to saline stressed conditions for growing at harsh land in Egypt. Therefore, seed lots of three cultivars and exotic variety (Bactol, Serow 4, Serow 6 and Evita) were subjected to 100,400 and 600 Gy of gamma rays. Mass selection with 20 % intensity for high number of pods per plant has been done in each treatment in M2 generation. However, individually plants with high number of pods / plant were selected from each variety in M3 generation for test under saline stressed conditions at Ras Sudr region in M4 (8600 and 8300 ppm salinity for soil and irrigation, respectively). The obtained results revealed that eight mutated families from 12- test families in M4 generation surpassed their parents in seed yield / plant and related characters ( plant height ,fruiting zone length , No. of branches , No. of pods / plant ). In addition, the mutant F93 characterized by fast growing and non shuttering pods reflecting 50.4% over Evita control in seed yield/ plant. Twelve mutant lines in M5 represented the mutant families were grown in sandy-loam soil at Inshas region. The three mutant lines (L 22, L 38 and L 45) continuously surpassed their parents in seed yield and related characters, but the increases were less than the previous generation. The increase was 22.3 %, 38.7 % and 36.7 % over seed yield of respective parents. Moreover, mutant L66 exhibited an increase in its yield components in M5 at Inshas only, suggesting that gene expression and genomic structure extremely influenced by environmental factors. Genetic stability for the obtained mutations could be done at different environmental conditions in further studies

  5. Cytokinins induce transcriptional reprograming and improve Arabidopsis plant performance under drought and salt stress conditions.

    Directory of Open Access Journals (Sweden)

    Natali Shirron

    2016-10-01

    Full Text Available In nature, annual plants respond to abiotic stresses by activating a specific genetic program leading to early flowering and accelerated senescence. Although, in nature, this phenomenon supports survival under unfavorable environmental conditions, it may have negative agro-economic impacts on crop productivity. Overcoming this genetic programing by cytokinins (CK has recently been shown in transgenic plants that overproduce CK. These transgenic plants displayed a significant increase in plant productivity under drought stress conditions. We investigated the role of CK in reverting the transcriptional program that is activated under abiotic stress conditions and allowing sustainable plant growth. We employed 2 complementary approaches: Ectopic overexpression of CK, and applying exogenous CK to detached Arabidopsis leaves. Transgenic Arabidopsis plants transformed with the isopentyltransferase (IPT gene under the regulation of the senescence associated receptor kinase (SARK promoter displayed a significant drought resistance. A transcriptomic analysis using RNA sequencing was performed to explore the response mechanisms under elevated CK levels during salinity stress. This analysis showed that under such stress, CK triggered transcriptional reprograming that resulted in attenuated stress-dependent inhibition of vegetative growth and delayed premature plant senescence. Our data suggest that elevated CK levels led to stress tolerance by retaining the expression of genes associated with plant growth and metabolism whose expression typically decreases under stress conditions. In conclusion, we hypothesize that CK allows sustainable plant growth under unfavorable environmental conditions by activating gene expression related to growth processes and by preventing the expression of genes related to the activation of premature senescence.

  6. Diet induced thermogenesis

    OpenAIRE

    Westerterp KR

    2004-01-01

    Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Resu...

  7. Analysis and modeling of unsteady aerodynamics with application to wind turbine blade vibration at standstill conditions

    Energy Technology Data Exchange (ETDEWEB)

    Skrzypinski, W.

    2012-02-15

    Wind turbine blade vibrations at standstill conditions were investigated in the present work. These included vortex-induced and stall-induced vibrations. Thus, it was investigated whether the stand still vibrations are vortex-induced, stall-induced or a combination of both types. The work comprised analyzes based on engineering models and Computational Fluid Dynamics. Two-dimensional, three-degree-of-freedom, elastically-mounted-airfoil engineering models were created. These models aimed at investigating the effect of temporal lag in the aerodynamic response of an airfoil on the aeroelastic stability limits. The motivation for it was that the standard aerodynamics existing in state-of-the-art aeroelastic codes is effectively quasi-steady in deep stall. If such an assumption was incorrect, these codes could predict stall-induced vibrations inaccurately. The main conclusion drawn from these analyses was that even a relatively low amount of temporal lag in the aerodynamic response may significantly increase the aerodynamic damping and therefore influence the aeroelastic stability limits, relative to quasisteady aerodynamic response. Two- and three-dimensional CFD computations included non-moving, prescribed-motion and elastically mounted airfoil suspensions. 2D and 3D prescribed-motion CFD computations performed on a DU96-W-180 airfoil predicted vortex-induced vibrations at 90 degrees angle of attack at the frequency close to the stationary vortex shedding frequency predicted by 2D CFD computations. Significant discrepancies were observed between 2D and 3D computations around 25 degrees angle of attack. 3D computations predicted occurrence of vortex-induced vibrations while the wind speed necessary for the occurrence of stall-induced vibrations was predicted too high to occur in normal conditions. Analysis of the dynamic lift and drag resulting from 2D and 3D CFD computations carried out around 25 degrees angle of attack showed loops with the slopes of opposite signs

  8. Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice.

    Science.gov (United States)

    Wu, Chia-Lung; McNeill, Jenna; Goon, Kelsey; Little, Dianne; Kimmerling, Kelly; Huebner, Janet; Kraus, Virginia; Guilak, Farshid

    2017-09-01

    To investigate whether short-term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity. CSF-1R-GFP+ macrophage Fas-induced apoptosis (MaFIA)-transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro-computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured. Macrophage-depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage-depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony-stimulating factor, interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion. Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity. © 2017, American College of Rheumatology.

  9. Characterization of six small HSP genes from Chironomus riparius (Diptera, Chironomidae): Differential expression under conditions of normal growth and heat-induced stress.

    Science.gov (United States)

    Martín-Folgar, Raquel; de la Fuente, Mercedes; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2015-10-01

    Small heat shock proteins (sHSPs) comprise the most numerous, structurally diverse, and functionally uncharacterized family of heat shock proteins. Several Hsp genes (Hsp 90, 70, 40, and 27) from the insect Chironomus riparius are widely used in aquatic toxicology as biomarkers for environmental toxins. Here, we conducted a comparative study and characterized secondary structure of the six newly identified sHsp genes Hsp17, Hsp21, Hsp22, Hsp23, Hsp24, and Hsp34. A characteristic α-crystallin domain is predicted in all the new proteins. Phylogenetic analysis suggests a strong relation to other sHSPs from insects and interesting evidence regarding evolutionary origin and duplication events. Comparative analysis of transcription profiles for Hsp27, Hsp70, and the six newly identified genes revealed that Hsp17, Hsp21, and Hsp22 are constitutively expressed under normal conditions, while under two different heat shock conditions these genes are either not activated or are even repressed (Hsp22). In contrast, Hsp23, Hsp24, and Hsp34 are significantly activated along with Hsp27 and Hsp70 during heat stress. These results strongly suggest functional differentiation within the small HSP subfamily and provide new data to help understand the coping mechanisms induced by stressful environmental stimuli. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Effect of superoxide dismutase and catalase on radiation-induced inhibition of human lymphocyte blastogenesis

    International Nuclear Information System (INIS)

    Knox, S.; Misra, H.P.; Rosenblatt, L.S.; Shifrine, M.

    1980-01-01

    Mitogen-induced lymphocyte blastogenesis was measured following x-irradiation (0 to 400 R) in the presence or absence of SOD, under aerobic or anaerobic conditions. No significant differences were observed between radiation survival curves under these different conditions. SOD had no radioprotective effect, and an o.e.r. of 1.11 was obtained, demonstrating the lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following x-irradiation at 200 R, neither SOD nor catalase, alone or together, added before or after irradiation, was radioprotective

  11. Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization.

    Science.gov (United States)

    Itzhak, Y; Martin, J L; Black, M D; Ali, S F

    1998-06-01

    Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH-induced

  12. Chinese Medicine Treatment for Afatinib-Induced Paronychia

    Directory of Open Access Journals (Sweden)

    Pei-Yuu Yang

    2017-01-01

    Full Text Available Afatinib (Gilotrif™ is widely used to treat patients with mutant activating epidermal growth factor receptor- (EGFR- dependent lung adenocarcinoma; however, it has various adverse side effects. Here, we report a patient with afatinib-induced paronychia. After Chinese medicine treatment with the well-known anticancer Chinese herbs, Jen-Ren-Hwo-Minq-Saan, and decoction of Ban-Zhi-Lian (Scutellaria barbata with Bai-Hua-She-She-Cao (Hedyotis diffusa Willd, patient’s condition was significantly improved. This shows that these Chinese medicines can not only be used in cancer treatment but also be used in the afatinib-induced paronychia.

  13. Angiogenesis is induced by airway smooth muscle strain.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D

    2007-10-01

    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD.

  14. Methylation-mediated silencing of miR-124 facilitates chondrogenesis by targeting NFATc1 under hypoxic conditions.

    Science.gov (United States)

    Gong, Ming; Liang, Tangzhao; Jin, Song; Dai, Xuejun; Zhou, Zhiyu; Gao, Manman; Huang, Sheng; Luo, Jiaquan; Zou, Lijin; Zou, Xuenong

    2017-01-01

    Chondrogenic differentiation of mesenchymal stem cells is regulated by many different pathways. Recent studies have established that hypoxia and epigenetic alterations potently affect expression of chondrogenesis marker genes. Sox9 is generally regarded as a master regulator of chondrogenesis and microRNA-124 (miRNA-124) regulates gene expression in murine bone marrow-derived mesenchymal stem cells. Therefore, in this study we investigated whether epigenetic regulation of miRNA-124 could affect the expression of Sox9 and thereby regulate chondrogenesis. A cell pellet culture model was used to induce chondrogenesis in C3H10T1/2 cells under hypoxic conditions (2% O 2 ) to determine the effects of hypoxia on miR-124 expression and DNA methylation. The expression of miR-124 was significantly downregulated under hypoxic conditions compared to normoxic conditions (21% O 2 ). The expression of chondrogenesis marker genes was significantly increased under hypoxic conditions. Bisulfite sequencing of the CpG islands in the promoter region of miR-124-3 showed that CpG methylation was significantly increased under hypoxic conditions. Treating the cells with the DNA demethylating agent 5'-AZA significantly increased miR-124 expression and decreased expression of markers of chondrogenesis. Overexpressing miR-124 under hypoxic conditions inhibited NFATc1 reporter activity. NFATc1 was shown to bind to the promoter region of Sox9. Taken together, our data provide evidence that miR-124 acts as an inhibitor of NFATc1. Under hypoxic conditions when miR-124 is downregulated by methylation of CpG islands in the promoter, NFATc1 can bind to the Sox9 promoter and induce the expression of Sox9 leading to chondrogenesis. These results support the role of epigenetic regulation in establishing and maintaining a chondrogenic phenotype.

  15. Activity of the Respiratory Chain Enzymes of Blood Leucocytes’ Mitochondria Under the Conditions of Toxic Hepatitis Induced Against the Background Alimentary Deprivation of Protein

    Directory of Open Access Journals (Sweden)

    O.N. Voloshchuk

    2015-12-01

    Full Text Available Full functioning of the leucocytes’ energy supply system is one of the essential factors for the immune surveillance system effective work. The pivotal enzymes of the leucocytes’ energy biotransformation system are NADH-ubiquitin reductase, a marker of the Complex I of respiratory chain activity, and succinate dehydrogenase, key enzyme of the Complex II of respiratory chain. The aim of research – to study the NADH-ubiquitin reductase and succinate dehydrogenase activity of the blood leucocytes’ mitochondria under the conditions of toxic hepatitis induced against the background alimentary deprivation of protein. It is shown, that under the conditions of acetaminophen-induced hepatitis a reduction of the NADH-ubiquitin reductase enzymatic activity is observed on the background activation of the succinate-dependent way of the mitochondrial oxidation. Conclusion was made that alimentary deprivation or protein is a factor, aggravating the misbalance of the energy biotransformation system in the leucocytes of rats with toxic hepatitis. Established activity changes of the leucocytes’ mitochondria respiratory chain key enzymes may be considered as one of the mechanisms, directed on the maintenance of leucocytes energy supply on a level, sufficient for their functioning. Research results may be used for the biochemical rationale of the therapeutic approaches to the elimination and correction of the leucocytes’ energy metabolism disturbances consequences under the conditions of acetaminophen-induced hepatitis, aggravated by the alimentary protein deprivation.

  16. Some conditions for significant contribution from photovoltaics to sustainable development

    International Nuclear Information System (INIS)

    Coiante, D.

    1994-03-01

    In medium-long term perspective, the anthropogenic atmospheric pollution, due to fossil fuel burning, could be contained by massively using of renewable energy. Significant improvements are expected to arise from diffusion into use of large scale PV power systems. Considering the situation in Italy as a typical study case, a limit can be individuated, which makes that PV contribution to annual electric energy balance can reach a maximum of about 7%. Such a figure corresponds to about 2% in terms of contribution to total energy balance. Thus, the intermittent energy sources are destined, in Italy, to be confined to a role, just significant (7%) in the electric energy sector, but quite marginal (2%) with reference to expected environmental massive benefits. Apart from numerical results, this disappointing concept can be applied in general to all OCSE countries, wich globally produce the largest amount of world pollutant energy. Consequently, if photovoltaics wants to acquire a real environmental consistence, the limit of PV system diffusion has to be overcome. This can be attained by implementing the present grid-tied reference model for PV system diffusion by including an hydrogen production and storage system

  17. Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

    DEFF Research Database (Denmark)

    Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

    2018-01-01

    and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...... in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels...

  18. Influence of cued-fear conditioning and its impairment on NREM sleep.

    Science.gov (United States)

    Kumar, Tankesh; Jha, Sushil K

    2017-10-01

    Many studies suggest that fear conditioning influences sleep. It is, however, not known if the changes in sleep architecture after fear conditioning are essentially associated with the consolidation of fearful memory or with fear itself. Here, we have observed that within sleep, NREM sleep consistently remained augmented after the consolidation of cued fear-conditioned memory. But a similar change did not occur after impairing memory consolidation by blocking new protein synthesis and glutamate transmission between glial-neuronal loop in the lateral amygdala (LA). Anisomycin (a protein synthesis inhibitor) and DL-α-amino-adipic acid (DL- α -AA) (a glial glutamine synthetase enzyme inhibitor) were microinjected into the LA soon after cued fear-conditioning to induce memory impairment. On the post-conditioning day, animals in both the groups exhibited significantly less freezing. In memory-consolidated groups (vehicle groups), NREM sleep significantly increased during 2nd to 5th hours after training compared to their baseline days. However, in memory impaired groups (anisomycin and DL- α -AA microinjected groups), similar changes were not observed. Our results thus suggest that changes in sleep architecture after cued fear-conditioning are indeed a consolidation dependent event. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Exercise-induced thallium-201 myocardial perfusion defects in angina pectoris without significant coronary artery stenosis

    International Nuclear Information System (INIS)

    Nakazato, Masayasu; Maruoka, Yuji; Sunagawa, Osahiko; Kinjo, Kunihiko; Tomori, Masayuki; Fukiyama, Koshiro

    1990-01-01

    We performed exercise thallium-201 myocardial scintigraphy in 32 patients with angina pectoris to study the incidence of perfusion defects, who had no significant organic stenosis on coronary angiography. None of them had myocardial infarction or cardiomyopathy. Thallium-201 myocardial scintigraphy and 12-lead ECG recording were performed during supine bicycle ergometer exercise. Perfusion defects in thallium-201 scintigrams in SPECT images were assessed during visual analysis by two observers. In the coronary angiograms obtained during intravenous infusion of nitroglycerin, the luminal diameter of 75% stenosis or less in the AHA classification was regarded as an insignificant organic stenosis. Myocardial perfusion defects in the thallium-201 scintigrams were detected in eight (25%) of the 32 patients. Six of these eight patients had variant angina documented during spontaneous attacks with ST elevations in standard 12-lead ECGs. Perfusion defects were demonstrated at the inferior or infero-posterior regions in six patients, one of whom had concomitant anteroseptal defect. The defects were not always accompanied by chest pain. All but one patient demonstrating inferior or inferoposterior defects showed ST depression in leads II, III and aV F on their ECGs, corresponding to inferior wall ischemia. The exception was a case with right bundle branch block. Thus, 25% of the patients with angina pectoris, who had no evidence of significant organic stenosis on their coronary angiograms, exhibited exercise-induced perfusion defects in their thallium-201 scintigrams. Coronary spasms might have caused myocardial ischemia in these patients. (author)

  20. Behaviour of electrical cables under fire conditions

    International Nuclear Information System (INIS)

    Bertrand, R.; Chaussard, M.; Gonzalez, R.; Lacoue, J.; Mattei, J.M.; Such, J.M.

    2002-01-01

    A Fire Probabilistic Safety Assessment - called the Fire PSA - is being carried out by the French Institute of Radiological Protection and Nuclear Safety (IPSN) to be used in the framework of the safety assessment of operating 900 MWe PWRs. The aim of this study is to evaluate the core damage conditional probability which could result from a fire. A fire can induce unavailability of safety equipment, notably damaging electrical cables introducing a significant risk contributor. The purpose of this paper is to present the electrical cable fire tests carried out by IPSN to identify the failure modes and to determine the cable damage criteria. The impact of each kind of cable failure mode and the methodology used to estimate the conditional probability of a failure mode when cable damage occurred is also discussed. (orig.) [de

  1. Aviation NOx-induced CH4 effect: Fixed mixing ratio boundary conditions versus flux boundary conditions

    Science.gov (United States)

    Khodayari, Arezoo; Olsen, Seth C.; Wuebbles, Donald J.; Phoenix, Daniel B.

    2015-07-01

    Atmospheric chemistry-climate models are often used to calculate the effect of aviation NOx emissions on atmospheric ozone (O3) and methane (CH4). Due to the long (∼10 yr) atmospheric lifetime of methane, model simulations must be run for long time periods, typically for more than 40 simulation years, to reach steady-state if using CH4 emission fluxes. Because of the computational expense of such long runs, studies have traditionally used specified CH4 mixing ratio lower boundary conditions (BCs) and then applied a simple parameterization based on the change in CH4 lifetime between the control and NOx-perturbed simulations to estimate the change in CH4 concentration induced by NOx emissions. In this parameterization a feedback factor (typically a value of 1.4) is used to account for the feedback of CH4 concentrations on its lifetime. Modeling studies comparing simulations using CH4 surface fluxes and fixed mixing ratio BCs are used to examine the validity of this parameterization. The latest version of the Community Earth System Model (CESM), with the CAM5 atmospheric model, was used for this study. Aviation NOx emissions for 2006 were obtained from the AEDT (Aviation Environmental Design Tool) global commercial aircraft emissions. Results show a 31.4 ppb change in CH4 concentration when estimated using the parameterization and a 1.4 feedback factor, and a 28.9 ppb change when the concentration was directly calculated in the CH4 flux simulations. The model calculated value for CH4 feedback on its own lifetime agrees well with the 1.4 feedback factor. Systematic comparisons between the separate runs indicated that the parameterization technique overestimates the CH4 concentration by 8.6%. Therefore, it is concluded that the estimation technique is good to within ∼10% and decreases the computational requirements in our simulations by nearly a factor of 8.

  2. Interrater and intrarater agreements of magnetic resonance imaging findings in the lumbar spine: significant variability across degenerative conditions.

    Science.gov (United States)

    Fu, Michael C; Buerba, Rafael A; Long, William D; Blizzard, Daniel J; Lischuk, Andrew W; Haims, Andrew H; Grauer, Jonathan N

    2014-10-01

    agreement. However, when stratified by condition, absolute interrater agreement ranged from 65.1% to 92.0%. Disc hydration, disc space height, and bone marrow changes exhibited the lowest absolute interrater agreements. The absolute intrarater agreement had a narrower range, from 74.5% to 91.5%. Fleiss kappa coefficients ranged from fair-to-substantial agreement (0.282-0.618). Even in a study using standardized evaluation criteria, there was significant variability in the interrater and intrarater agreements of MRI in assessing different degenerative conditions of the lumbar spine. Clinicians should be aware of the condition-specific diagnostic limitations of MRI interpretation. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Light-induced aggregation of microbial exopolymeric substances.

    Science.gov (United States)

    Sun, Luni; Xu, Chen; Zhang, Saijin; Lin, Peng; Schwehr, Kathleen A; Quigg, Antonietta; Chiu, Meng-Hsuen; Chin, Wei-Chun; Santschi, Peter H

    2017-08-01

    Sunlight can inhibit or disrupt the aggregation process of marine colloids via cleavage of high molecular weight compounds into smaller, less stable fragments. In contrast, some biomolecules, such as proteins excreted from bacteria can form aggregates via cross-linking due to photo-oxidation. To examine whether light-induced aggregation can occur in the marine environment, we conducted irradiation experiments on a well-characterized protein-containing exopolymeric substance (EPS) from the marine bacterium Sagitulla stellata. Our results show that after 1 h sunlight irradiation, the turbidity level of soluble EPS was 60% higher than in the dark control. Flow cytometry also confirmed that more particles of larger sized were formed by sunlight. In addition, we determined a higher mass of aggregates collected on filter in the irradiated samples. This suggests light can induce aggregation of this bacterial EPS. Reactive oxygen species hydroxyl radical and peroxide played critical roles in the photo-oxidation process, and salts assisted the aggregation process. The observation that Sagitulla stellata EPS with relatively high protein content promoted aggregation, was in contrast to the case where no significant differences were found in the aggregation of a non-protein containing phytoplankton EPS between the dark and light conditions. This, together with the evidence that protein-to-carbohydrate ratio of aggregates formed under light condition is significantly higher than that formed under dark condition suggest that proteins are likely the important component for aggregate formation. Light-induced aggregation provides new insights into polymer assembly, marine snow formation, and the fate/transport of organic carbon and nitrogen in the ocean. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  5. Conditioned taste aversion prevents the long-lasting BDNF-induced enhancement of synaptic transmission in the insular cortex: A metaplastic effect.

    Science.gov (United States)

    Rivera-Olvera, Alejandro; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-04-01

    Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Atmospheric particle formation in spatially and temporally varying conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lauros, J.

    2011-07-01

    Atmospheric particles affect the radiation balance of the Earth and thus the climate. New particle formation from nucleation has been observed in diverse atmospheric conditions but the actual formation path is still unknown. The prevailing conditions can be exploited to evaluate proposed formation mechanisms. This study aims to improve our understanding of new particle formation from the view of atmospheric conditions. The role of atmospheric conditions on particle formation was studied by atmospheric measurements, theoretical model simulations and simulations based on observations. Two separate column models were further developed for aerosol and chemical simulations. Model simulations allowed us to expand the study from local conditions to varying conditions in the atmospheric boundary layer, while the long-term measurements described especially characteristic mean conditions associated with new particle formation. The observations show statistically significant difference in meteorological and back-ground aerosol conditions between observed event and non-event days. New particle formation above boreal forest is associated with strong convective activity, low humidity and low condensation sink. The probability of a particle formation event is predicted by an equation formulated for upper boundary layer conditions. The model simulations call into question if kinetic sulphuric acid induced nucleation is the primary particle formation mechanism in the presence of organic vapours. Simultaneously the simulations show that ignoring spatial and temporal variation in new particle formation studies may lead to faulty conclusions. On the other hand, the theoretical simulations indicate that short-scale variations in temperature and humidity unlikely have a significant effect on mean binary water sulphuric acid nucleation rate. The study emphasizes the significance of mixing and fluxes in particle formation studies, especially in the atmospheric boundary layer. The further

  7. Clinical significance of changes of plasma ET, NO, THcy and cystatin C levels in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Yu Qiuyue

    2009-01-01

    Objective: To investigate the relationship between development of illness and changes of plasma endothelin (ET) nitric oxide (NO), total homocysteine (THcy) and Cystatin C (Cyst C) levels in patients with pregnancy induced Hypertension. Methods: Plasma levels of ET, THcy (with RIA), NO (with chemical Greiss method) and Cyst C (with particle enhanced) immunoneph-elometric assay (PETIA) in 32 patients with PIH, 35 non-pregnant women and 35 normal pregnant women. Results: The plasma ET, NO levels were significantly higher in 35 normal pregnant women than those in the healthy non-pregnantwomen (all P 0.05). Plasma ET levels and THcy, Cyst C levels were mutually positivety correlated (r=0.6097, 0.7213, all P<0.01), while the plasma ET levels and NO levels were negatively correlated (r=0.5812, P<0.01). Conclusion: Determination of changes of plasma ET, NO, THcy and Cyst C levels in patients with Pregnancy induced Hypertension were helpful for disease mechanism elucidation and outcome prediction. (authors)

  8. Application of Laser Induced Breakdown Spectroscopy under Polar Conditions

    Science.gov (United States)

    Clausen, J. L.; Hark, R.; Bol'shakov, A.; Plumer, J.

    2015-12-01

    Over the past decade our research team has evaluated the use of commercial-off-the-shelf laser-induced breakdown spectroscopy (LIBS) for chemical analysis of snow and ice samples under polar conditions. One avenue of research explored LIBS suitability as a detector of paleo-climate proxy indicators (Ca, K, Mg, and Na) in ice as it relates to atmospheric circulation. LIBS results revealed detection of peaks for C and N, consistent with the presence of organic material, as well as major ions (Ca, K, Mg, and Na) and trace metals (Al, Cu, Fe, Mn, Ti). The detection of Ca, K, Mg, and Na confirmed that LIBS has sufficient sensitivity to be used as a tool for characterization of paleo-climate proxy indicators in ice-core samples. Techniques were developed for direct analysis of ice as well as indirect measurements of ice via melting and filtering. Pitfalls and issues of direct ice analysis using several cooling techniques to maintain ice integrity will be discussed. In addition, a new technique, laser ablation molecular isotopic spectroscopy (LAMIS) was applied to detection of hydrogen and oxygen isotopes in ice as isotopic analysis of ice is the main tool in paleoclimatology and glaciology studies. Our results demonstrated that spectra of hydroxyl isotopologues 16OH, 18OH, and 16OD can be recorded with a compact spectrograph to determine hydrogen and oxygen isotopes simultaneously. Quantitative isotopic calibration for ice analysis can be accomplished using multivariate chemometric regression as previously realized for water vapor. Analysis with LIBS and LAMIS required no special sample preparation and was about ten times faster than analysis using ICP-MS. Combination of the two techniques in one portable instrument for in-field analysis appears possible and would eliminate the logistical and cost issues associated with ice core management.

  9. The significant role of plasmonic effects in femtosecond laser-induced grating fabrication on the nanoscale

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Min; Zhao, Fuli [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou, 510275 (China); Cheng, Ya; Xu, Zhizhan [State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, P.O. Box 800-211, Shanghai, 201800 (China)

    2013-02-15

    Nowadays, plasmonics aiming at manipulating light beyond the diffraction limit has aroused great interest on account of the promise of nanoscale optical devices. Generally, the ability to break diffraction barrier is achieved via controlling surface plasmons (SPs) on artificial structures as products of human ingenuity. Here, nevertheless, it is demonstrated that in short-pulse laser ablation ultrafast active plasmonic structures spontaneously generate by virtue of plasmonic effects rather than human will. First, with the experimental results on ZnO, Si, and GaAs, explicit evidence is provided for the grating-splitting phenomenon that acts as a direct route for the formation of laser-induced deep-subwavelength gratings. The splitting mechanism can break through the diffraction limit and push laser-induced structures towards the nanoscale. Then, through comprehensive numerical studies based on the viewpoint of plasmonics, it can be confirmed that the grating-splitting phenomenon originates in the conversion of SP modes from the resonant to the nonresonant mode and further to the inphase or antiphase asymmetric mode. In short, plasmonic effects play an important role in ultrafast laser-induced grating splitting towards the nanoscale, which will provide new insights into the mechanisms of ultrafast laser-induced nanostructures. (copyright 2012 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. The significant role of plasmonic effects in femtosecond laser-induced grating fabrication on the nanoscale

    International Nuclear Information System (INIS)

    Huang, Min; Zhao, Fuli; Cheng, Ya; Xu, Zhizhan

    2013-01-01

    Nowadays, plasmonics aiming at manipulating light beyond the diffraction limit has aroused great interest on account of the promise of nanoscale optical devices. Generally, the ability to break diffraction barrier is achieved via controlling surface plasmons (SPs) on artificial structures as products of human ingenuity. Here, nevertheless, it is demonstrated that in short-pulse laser ablation ultrafast active plasmonic structures spontaneously generate by virtue of plasmonic effects rather than human will. First, with the experimental results on ZnO, Si, and GaAs, explicit evidence is provided for the grating-splitting phenomenon that acts as a direct route for the formation of laser-induced deep-subwavelength gratings. The splitting mechanism can break through the diffraction limit and push laser-induced structures towards the nanoscale. Then, through comprehensive numerical studies based on the viewpoint of plasmonics, it can be confirmed that the grating-splitting phenomenon originates in the conversion of SP modes from the resonant to the nonresonant mode and further to the inphase or antiphase asymmetric mode. In short, plasmonic effects play an important role in ultrafast laser-induced grating splitting towards the nanoscale, which will provide new insights into the mechanisms of ultrafast laser-induced nanostructures. (copyright 2012 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Clinical significance of determination of changes of serum Hcy, ET and BNP levels After treatment in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    He Hongling

    2010-01-01

    Objective: To study the clinical significance of changes of serum Hcy, ET and BNP levels after treatment in patients with pregnancy induced hypertension(PIH). Methods: Serum Hcy (with ELISA), ET and BNP (with RIA) levels were determined in 32 patients with PIH both before and after treatment as well as in 35 controls. Results: Before treatment, serum Hcy, ET and BNP levels in patients with PIH were significantly higher than those in controls (P < 0.01). After 1 month of treatment the levels dropped markedly, but still remained significantly higher(P < 0.05). Conclusion: Serum Hcy, ET and BNP levels were closely related to the diseases process of PIH and were of prognostic values. (authors)

  12. Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

    International Nuclear Information System (INIS)

    Bache, Matthias; Taubert, Helge; Vordermark, Dirk; Zschornak, Martin P; Passin, Sarina; Keßler, Jacqueline; Wichmann, Henri; Kappler, Matthias; Paschke, Reinhard; Kaluđerović, Goran N; Kommera, Harish

    2011-01-01

    Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC 50 ) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Our results suggest that BA is capable

  13. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    International Nuclear Information System (INIS)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O

    2010-01-01

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As x Se 100-x (10 ≤ x ≤ 42) and As x S 100-x (30 ≤ x ≤ 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As x S 100-x within 30 ≤ x x Se 100-x glasses from the same compositional interval do not show any measurable changes in DSC curves after γ-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of γ-induced excitations within sulfur-based network in comparison with selenium-based one.

  14. [Etiological analysis and significance of anterior knee pain induced by gluteal muscles contracture].

    Science.gov (United States)

    Zhao, Gang; Liu, Yu-jie; Wang, Jun-liang; Qi, Wei; Qu, Feng; Yuan, Bang-tuo; Wang, Jiang-tao; Shen, Xue-zhen; Liu, Yang; Zhu, Juan-li

    2014-12-01

    To explore causes of gluteal muscle contracture induced anterior knee pain and curative effect of arthroscopic release. From March 2002 to August 2013,36 patients with gluteal muscle contracture induced anterior knee pain were treated, including 15 males, 21 females, aged from 9 to 40 years old with an average (18.7±7.2) years old; the courses of diseases ranged from 4 to 30 years. The clinical manifestations involved limited to symmelia, positive Ober sign, buttocks touch contracture belts, knee and patella slide to lateral when doing squat activities. All patients were performed gluteal muscle contracture release under arthroscopic. Postoperative complications were observed, Kujala scoring before and after operation was used for compare curative effect. All patients were followed up with an average of 29 months. The incision were healed well, and no complications were occurred. Postoperative Kujala score were improved more than preoperative. Gluteal muscle contracture release could alleviate hypertension of lateral patella, and palys an important role in preventing patellofemoral arthritis.

  15. Gallic Acid Decreases Inflammatory Cytokine Secretion Through Histone Acetyltransferase/Histone Deacetylase Regulation in High Glucose-Induced Human Monocytes.

    Science.gov (United States)

    Lee, Wooje; Lee, Sang Yeol; Son, Young-Jin; Yun, Jung-Mi

    2015-07-01

    Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.

  16. Serotonergic Modulation of Conditioned Fear

    Directory of Open Access Journals (Sweden)

    Judith R. Homberg

    2012-01-01

    Full Text Available Conditioned fear plays a key role in anxiety disorders as well as depression and other neuropsychiatric conditions. Understanding how neuromodulators drive the associated learning and memory processes, including memory consolidation, retrieval/expression, and extinction (recall, is essential in the understanding of (individual differences in vulnerability to these disorders and their treatment. The human and rodent studies I review here together reveal, amongst others, that acute selective serotonin reuptake inhibitor (SSRI treatment facilitates fear conditioning, reduces contextual fear, and increases cued fear, chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors inhibit the acquisition and expression of contextual fear, 5-HT2A receptors facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor mediates contextual fear, genetically induced increases in serotonin levels are associated with increased fear conditioning, impaired cued fear extinction, or impaired extinction recall, and that genetically induced 5-HT depletion increases fear conditioning and contextual fear. Several explanations are presented to reconcile seemingly paradoxical relationships between serotonin levels and conditioned fear.

  17. Programmed cell death of tobacco BY-2 cells induced by still culture conditions is affected by the age of the culture under agitation.

    Science.gov (United States)

    Hiraga, Asahi; Kaneta, Tsuyoshi; Sato, Yasushi; Sato, Seiichi

    2010-01-25

    Evans Blue staining indicated that actively growing tobacco BY-2 cells in the exponential phase died more rapidly than quiescent cells in the stationary phase when the cells cultured under agitation were placed under still conditions. Fifty percent cell death was induced at about 18, 26, 80 and 140 h for early, mid, late exponential- and stationary-phase cells, respectively. Actively growing cells became TUNEL (transferase-mediated dUTP nick end labelling)-positive more rapidly than quiescent cells, suggesting that the cell death evaluated by Evans Blue is accompanied by DNA cleavages. Electrophoresis of genomic DNA showed a typical 'DNA laddering' pattern formed by multiples of about 200 bp internucleosomal units. Chromatin condensation was first detected at least within 24 h by light microscopy, and then cell shrinkage followed. These findings suggest that the death of BY-2 cells induced by still conditions is PCD (programmed cell death).

  18. The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

    International Nuclear Information System (INIS)

    Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

    2004-01-01

    Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

  19. Matching conditions for a brane of arbitrary codimension

    International Nuclear Information System (INIS)

    Charmousis, Christos; Zegers, Robin

    2005-01-01

    We present matching conditions for distributional sources of arbitrary codimension in the context of Lovelock gravity. Then we give examples, treating maximally symmetric distributional p-branes, embedded in flat, de Sitter and anti-de Sitter spacetime. Unlike Einstein theory, distributional defects of locally smooth geometry and codimension greater than 2 are demonstrated to exist in Lovelock theories. The form of the matching conditions depends on the parity of the brane codimension. For odd codimension, the matching conditions involve discontinuities of Chern-Simons forms and are thus similar to junction conditions for hypersurfaces. For even codimension, the bulk Lovelock densities induce intrinsic Lovelock densities on the brane. In particular, this results in the appearance of the induced Einstein tensor for p>2. For the matching conditions we present, the effect of the bulk is reduced to an overall topological solid angle defect which sets the Planck scale on the brane and to extrinsic curvature terms. Moreover, for topological matching conditions and solid deficit angle, we find that the equations of motion are obtained from an exact p+1 dimensional action, which reduces to an induced Lovelock theory for large codimension. In essence, this signifies that the distributional part of the Lovelock bulk equations can naturally give rise to induced gravity terms on a brane of even co-dimension. We relate our findings to recent results on codimension 2 branes

  20. General anesthetics inhibit erythropoietin induction under hypoxic conditions in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Tomoharu Tanaka

    Full Text Available Erythropoietin (EPO, originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS. EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes.BALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10-1.0%. Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2α protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2α protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2α protein and EPO mRNA.Taken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibit hypoxia-induced EPO upregulation in the mouse brain through a direct effect on astrocytes.

  1. Impact of oxidative stress defense on bacterial survival and morphological change in Campylobacter jejuni under aerobic conditions

    Directory of Open Access Journals (Sweden)

    Euna eOh

    2015-04-01

    Full Text Available Campylobacter jejuni, a microaerophilic foodborne pathogen, inescapably faces high oxygen tension during its transmission to humans. Thus, the ability of C. jejuni to survive under oxygen-rich conditions may significantly impact C. jejuni viability in food and food safety as well. In this study, we investigated the impact of oxidative stress resistance on the survival of C. jejuni under aerobic conditions by examining three mutants defective in key antioxidant genes, including ahpC, katA, and sodB. All the three mutants exhibited growth reduction under aerobic conditions compared to the wild type (WT, and the ahpC mutant showed the most significant growth defect. The CFU reduction in the mutants was recovered to the WT level by complementation. Higher levels of reactive oxygen species (ROS were accumulated in C. jejuni under aerobic conditions than microaerobic conditions, and supplementation of culture media with an antioxidant recovered the growth of C. jejuni. The levels of lipid peroxidation and protein oxidation were significantly increased in the mutants compared to WT. Additionally, the mutants exhibited different morphological changes under aerobic conditions. The ahpC and katA mutants developed coccoid morphology by aeration, whereas the sodB mutant established elongated cellular morphology. Compared to microaerobic conditions, interestingly, aerobic culture conditions substantially induced the formation of coccoidal cells, and antioxidant treatment reduced the emergence of coccoid forms under aerobic conditions. The ATP concentrations and PMA-qPCR analysis supported that oxidative stress is a factor that induces the development of a viable-but-non-culturable (VBNC state in C. jejuni. The findings in this study clearly demonstrated that oxidative stress resistance plays an important role in the survival and morphological changes of C. jejuni under aerobic conditions.

  2. Self-selected music-induced reduction of perceived exertion during moderate-intensity exercise does not interfere with post-exercise improvements in inhibitory control.

    Science.gov (United States)

    Tanaka, Daichi; Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Hamaoka, Takafumi; Hashimoto, Takeshi; Isaka, Tadao

    2018-05-26

    Acute aerobic exercise improves inhibitory control (IC). This improvement is often associated with increases in perceived exertion during exercise. However, listening to music during aerobic exercise mitigates an exercise-induced increase in perceived exertion. Thus, it is hypothesized that such effects of music may interfere with exercise-induced improvements in IC. To test this hypothesis, we examined the effect of music on post-exercise IC improvements that were induced by moderate-intensity exercise. Fifteen healthy young men performed cycle ergometer exercise with music or non-music. The exercise was performed using a moderate-intensity of 60% of VO 2 peak for 30 min. The music condition was performed while listening to self-selected music. The non-music condition involved no music. To evaluate IC, the Stroop task was administered before exercise, immediately after exercise, and during the 30-min post-exercise recovery period. The rate of perceived exertion immediately before moderate-intensity exercise completed was significantly lower in music condition than in non-music condition. The IC significantly improved immediately after exercise and during the post-exercise recovery period compared to before exercise in both music and non-music conditions. The post-exercise IC improvements did not significantly differ between the two conditions. These findings indicate that self-selected music-induced mitigation of the increase in perceived exertion during moderate-intensity exercise dose not interfere with exercise-induced improvements in IC. Therefore, we suggest that listening to music may be a beneficial strategy in mitigating the increase in perceived exertion during aerobic exercise without decreasing the positive effects on IC. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Clinically Significant Contrast Induced Acute Kidney Injury after Non-Emergent Cardiac Catheterization - Risk Factors and Impact on Length of Hospital Stay

    International Nuclear Information System (INIS)

    Kashif, W.; Yaqub, S.; Khawaja, A.

    2013-01-01

    Objective: To evaluate the frequency and risk factors associated with clinically significant contrast-induced nephropathy (CIN) in patients undergoing non-emergent coronary angiography. Study Design: Descriptive study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from January 2005 to December 2007. Methodology: Case records of patients who underwent coronary angiography with a serum creatinine of >= 1.5 mg/dl at the time of procedure were evaluated. Clinically significant contrast induced nephropathy (CSCIN) was defined as either doubling of serum creatinine from baseline value within a week following the procedure or need for emergency hemodialysis after the procedure. Results: One hundred and sixteen patients met the inclusion criteria. Mean age was 64.0 +- 11.5 years, 72% were males. Overall prevalence of CIN was 17% (rise of serum creatinine by A= 0.5 mg/dl) while that of clinically significant CIN (CSCIN) was 9.5% (11 patients). Patients with CSCIN had significantly lower left ventricular ejection fraction (p = 0.03, OR: 0.24; 95% CI = 0.06 A= 0.91) and higher prevalence of cerebrovascular disease (p < 0.001, OR: 14.66; 95% CI = 3.30 - 65.08). Mean baseline serum creatinine was significantly higher, 3.0 +- 1.5 vs. 2.0 +- 1.1 mg/dl (p = 0.03, OR: 1.47; 95% CI = 1.03 - 2.11) whereas mean GFR estimated by Cockcroft-Gault formula was significantly lower at 25 +- 7.4 vs. 41.0 +- 14.6 ml/minute (p = 0.001, OR = 0.89, 95% CI = 0.84 A= 0.95) at the time of procedure in patients with CSCIN. Mean length of hospital stay was significantly higher in this group compared to those without CIN, 9.0 +- 5.1 vs. 3.0 +- 3.2 days (p = 0.001, OR = 1.31, 95% CI = 1.12 - 1.54). Multivariate analysis revealed low GFR (p = 0.001, OR = 0.88; 95% CI = 0.82 - 0.95) and low ejection fraction (p = 0.03, OR = 0.20; 95% CI = 0.04 - 0.91) to be independent factors associated with CSCIN. No significant differences were noted between the two groups in patients with

  4. Low temperature conditioning of garlic (Allium sativum L. "seed" cloves induces alterations in sprouts proteome

    Directory of Open Access Journals (Sweden)

    Miguel David Dufoo-Hurtado

    2015-05-01

    Full Text Available Low-temperature conditioning of garlic seed cloves substitutes the initial climatic requirements of the crop and accelerates the cycle. We have reported that seed bulbs from ‘Coreano’ variety conditioned at 5 °C for five weeks reduces growth and plant weight as well as the crop yields and increases the synthesis of phenolic compounds and anthocyanins. Therefore, this treatment suggests a cold stress. Plant acclimation to stress is associated with deep changes in proteome composition. Since proteins are directly involved in plant stress response, proteomics studies can significantly contribute to unravel the possible relationships between protein abundance and plant stress acclimation. The aim of this work was to study the changes in the protein profiles of garlic seed cloves subjected to conditioning at low-temperature using proteomics approach. Two sets of garlic bulbs were used, one set was stored at room temperature (23 °C, and the other was conditioned at low temperature (5 °C for five weeks. Total soluble proteins were extracted from sprouts of cloves and separated by two-dimensional gel electrophoresis. Protein spots showing statistically significant changes in abundance were analyzed by LC-ESI-MS/MS and identified by database search analysis using the Mascot search engine. The results revealed that low-temperature conditioning of garlic seed cloves causes alterations in the accumulation of proteins involved in different physiological processes such as cellular growth, antioxidative/oxidative state, macromolecules transport, protein folding and transcription regulation process. The metabolic pathways affected include protein biosynthesis and quality control system, photosynthesis, photorespiration, energy production, and carbohydrate and nucleotide metabolism. These processes can work cooperatively to establish a new cellular homeostasis that might be related with the physiological and biochemical changes observed in previous

  5. Impact of pavement conditions on crash severity.

    Science.gov (United States)

    Li, Yingfeng; Liu, Chunxiao; Ding, Liang

    2013-10-01

    Pavement condition has been known as a key factor related to ride quality, but it is less clear how exactly pavement conditions are related to traffic crashes. The researchers used Geographic Information System (GIS) to link Texas Department of Transportation (TxDOT) Crash Record Information System (CRIS) data and Pavement Management Information System (PMIS) data, which provided an opportunity to examine the impact of pavement conditions on traffic crashes in depth. The study analyzed the correlation between several key pavement condition ratings or scores and crash severity based on a large number of crashes in Texas between 2008 and 2009. The results in general suggested that poor pavement condition scores and ratings were associated with proportionally more severe crashes, but very poor pavement conditions were actually associated with less severe crashes. Very good pavement conditions might induce speeding behaviors and therefore could have caused more severe crashes, especially on non-freeway arterials and during favorable driving conditions. In addition, the results showed that the effects of pavement conditions on crash severity were more evident for passenger vehicles than for commercial vehicles. These results provide insights on how pavement conditions may have contributed to crashes, which may be valuable for safety improvement during pavement design and maintenance. Readers should notice that, although the study found statistically significant effects of pavement variables on crash severity, the effects were rather minor in reality as suggested by frequency analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Augmentation of the development of behavioral tolerance to cannabinoid administration through pavlovian conditioning.

    Science.gov (United States)

    Hill, Matthew N; Gorzalka, Boris B; Choi, Joyce W

    2004-01-01

    This investigation examined the effects, in female rats, of a Pavlovian conditioning paradigm on the development of tolerance to hypolocomotion induced by the cannabinoid agonist HU-210. Rats were administered HU-210 and placebo in either an associative or a nonassociative fashion. The results indicated that rats in the associative paradigm developed tolerance significantly faster than those in the nonassociative group (p conditioning, but that these physiological alterations are not contingent upon the associative parameters used for drug administration. Copyright 2004 S. Karger AG, Basel

  7. Effect of Locomotor Respiratory Coupling Induced by Cortical Oxygenated Hemoglobin Levels During Cycle Ergometer Exercise of Light Intensity.

    Science.gov (United States)

    Oyanagi, Keiichi; Tsubaki, Atsuhiro; Yasufuku, Yuichi; Takai, Haruna; Kera, Takeshi; Tamaki, Akira; Iwata, Kentaro; Onishi, Hideaki

    This study aimed to clarify the effects of locomotor-respiratory coupling (LRC) induced by light load cycle ergometer exercise on oxygenated hemoglobin (O2Hb) in the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), and sensorimotor cortex (SMC). The participants were 15 young healthy adults (9 men and 6 women, mean age: 23.1 ± 1.8 (SEM) years). We conducted a task in both LRC-inducing and LRC-non-inducing conditions for all participants. O2Hb was measured using near-infrared spectroscopy. The LRC frequency ratio during induction was 2:1; pedaling rate, 50 rpm; and intensity of load, 30 % peak volume of oxygen uptake. The test protocol included a 3-min rest prior to exercise, steady loading motion for 10 min, and 10-min rest post exercise (a total of 23 min). In the measurement of O2Hb, we focused on the DLPFC, SMA, and SMC. The LRC frequency was significantly higher in the LRC-inducing condition (p < 0.05). O2Hb during exercise was significantly lower in the DLPFC and SMA, under the LRC-inducing condition (p < 0.05). The study revealed that even light load could induce LRC and that O2Hb in the DLPFC and SMA decreases during exercise via LRC induction.

  8. 5-HT2A Serotonin Receptor Density in Adult Male Rats’ Hippocampus after Morphine-based Conditioned Place Preference

    Directory of Open Access Journals (Sweden)

    Rabie Mohammadi

    2016-07-01

    Conclusion: We concluded that the phenomenon of conditioned place preference induced by morphine can cause a significant increase in the number of serotonin 5-HT2A receptors in neurons of all areas of hippocampus.

  9. Clinical, cardiopulmonary and haemocytological effects of xylazine in goats after acute exposure to different environmental temperature and humidity conditions

    Directory of Open Access Journals (Sweden)

    E.G.M. Mogoa

    2000-07-01

    Full Text Available This study was carried out to assess the influence of xylazine administration on clinical, cardiopulmonary and haemocytological variables after acute exposure to different environmental conditions. Xylazine hydrochloride was administered intravenously at 0.1 mg/kg body mass to 6 clinically healthy, castrated male goats. All animals were exposed for 60 min to 3 sets of climatic conditions: 14 °C, 33% relative humidity; 24 °C, 55% RH, and 34 °C, 65% RH. The variables that were measured for a period of 60 min after xylazine administration were sedation, analgesia, salivation, urination, ventilation rate, heart-rate, mean arterial blood pressure, oesophageal temperature, haematocrit, mean corpuscular volume and mean corpuscular haemoglobin concentration. Xylazine induced sedation, analgesia, salivation and urination independently of the 3 environmental conditions. Environment had no influence on the onset, duration and recovery from sedation. In the 14 °C environment, xylazine resulted in a significant decrease in ventilation and heart-rate from baseline values. Significant changes in mean arterial blood pressure, haemoglobin concentration, mean corpuscular volume, haematocrit and red cell count were observed in the 3 environments. Total plasma protein was significantly altered at 24 °C and 34 °C. Acute exposure of goats to different environmental conditions had no significant influence on the clinical, cardiopulmonary and haemocytological variables. Physiological changes induced by xylazine were therefore independent of the environment.

  10. Climatic impact of aircraft induced ozone changes

    Energy Technology Data Exchange (ETDEWEB)

    Sausen, R; Feneberg, B; Ponater, M [Deutsche Forschungs- und Versuchsanstalt fuer Luft- und Raumfahrt e.V., Oberpfaffenhofen (Germany). Inst. fuer Physik der Atmosphaere

    1998-12-31

    The effect of aircraft induced ozone changes on the global climate is studied by means of the general circulation model ECHAM4. The zonal mean temperature signal is considered. In order to estimate the statistical significance of the climatic impact a multivariate statistical test hierarchy combined with the fingerprint method has been applied. Sensitivity experiments show a significant coherent temperature response pattern in the northern extra-tropics for mid-latitude summer conditions. It consists of a tropospheric warming of about 0.2 K with a corresponding stratospheric cooling of the same magnitude. (author) 16 refs.

  11. Climatic impact of aircraft induced ozone changes

    Energy Technology Data Exchange (ETDEWEB)

    Sausen, R.; Feneberg, B.; Ponater, M. [Deutsche Forschungs- und Versuchsanstalt fuer Luft- und Raumfahrt e.V., Oberpfaffenhofen (Germany). Inst. fuer Physik der Atmosphaere

    1997-12-31

    The effect of aircraft induced ozone changes on the global climate is studied by means of the general circulation model ECHAM4. The zonal mean temperature signal is considered. In order to estimate the statistical significance of the climatic impact a multivariate statistical test hierarchy combined with the fingerprint method has been applied. Sensitivity experiments show a significant coherent temperature response pattern in the northern extra-tropics for mid-latitude summer conditions. It consists of a tropospheric warming of about 0.2 K with a corresponding stratospheric cooling of the same magnitude. (author) 16 refs.

  12. Flow induced vibrations of the CLIC X-Band accelerating structures

    CERN Document Server

    Charles, Tessa; Boland, Mark; Riddone, Germana; Samoshkin, Alexandre

    2011-01-01

    Turbulent cooling water in the Compact Linear Collider (CLIC) accelerating structures will inevitably induce some vibrations. The maximum acceptable amplitude of vibrations is small, as vibrations in the accelerating structure could lead to beam jitter and alignment difficulties. A Finite Element Analysis model is needed to identify the conditions under which turbulent instabilities and significant vibrations are induced. Due to the orders of magnitude difference between the fluid motion and the structure’s motion, small vibrations of the structure will not contribute to the turbulence of the cooling fluid. Therefore the resonant conditions of the cooling channels presented in this paper, directly identify the natural frequencies of the accelerating structures to be avoided under normal operating conditions. In this paper a 2D model of the cooling channel is presented finding spots of turbulence being formed from a shear layer instability. This effect is observed through direct visualization and wavelet ana...

  13. Training for Translocation: Predator Conditioning Induces Behavioral Plasticity and Physiological Changes in Captive Eastern Hellbenders (Cryptobranchus alleganiensis alleganiensis (Cryptobranchidae, Amphibia

    Directory of Open Access Journals (Sweden)

    Erin K. Kenison

    2018-03-01

    Full Text Available Translocations are stressful, especially when captive animals are naïve to natural stimuli. Captive eastern hellbenders (Cryptobranchus alleganiensis alleganiensis identify predatory fish as threats, but may be more vulnerable to predation and stress because of inexperience with them. We investigated the use of predator conditioning to prepare hellbenders, behaviorally and physiologically, for the presence of a common predator, largemouth bass (Micropterus salmoides. We reared hellbenders for 30 d with and without continuous exposure to largemouth bass kairomones and heterospecific alarm cues and found conditioned hellbenders became less active compared to unconditioned individuals (p = 0.017. After conditioning, we exposed hellbenders to water, a low concentration of kairomones, or a high concentration of kairomones in a closed respirometer system. We measured activity within respirometer chambers and routine metabolic rate. We found unconditioned hellbenders exposed to low and high concentrations of kairomones were 41% and 119% more active than conditioned animals (p = 0.002 and p < 0.001. Moreover, conditioned individuals had on average 6.5% lower metabolic rates across all three kairomone concentrations compared to unconditioned individuals (p = 0.017. Our data suggest that predator conditioning induces behavioral avoidance tactics and physiological changes that could improve future translocation efforts for hellbenders and other imperiled species.

  14. Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

    Science.gov (United States)

    Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

    2017-07-01

    The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

  15. Synthesis of hydroxyapatite in the presence of biologically significant molecules

    International Nuclear Information System (INIS)

    Alvarez, R.; Evans, L.A.

    2000-01-01

    In bone mineralization non-collagenous phosphoproteins containing polycarboxylate sequences are thought to control crystal nucleation and to subsequently modify crystal growth. Invertebrate calcified tissues may also contain significant amounts of phosphoserine and/or acidic amino acid residues together with chitin (a polysaccharide). The present study investigated the effect of synthetic phosphorylated compounds as well as monomeric/polymeric carboxylic acid compounds on the formation of hydroxyapatite (HAp) under conditions of physiological pH, temperature and ionic strength. Poly-L-sodium aspartate was found to have the greatest inhibitory effect; only octacalcium phosphate (a known precursor of hydroxyapatite) could be detected in the presence of this polymer. Resultant minerals showed a variety of aggregation states. The biomimetically formed calcium phosphate minerals were identified and characterised by a variety of analytical thechniques, including laser Raman, Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy and x-ray diffraction analysis. In addition, a series of experiments were performed to induce the formation of HAp on biogenic substrates, such as chitin and its derivatives, chitosan, reconstituted chitin and phosphorylated chitin. Granular aggregates of hydroxyapatite could be induced to form directly on phosphorylated chitin surfaces, but not on other biogenically-derived substrates. Copyright (2000) The Australian Ceramic Society

  16. Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

    Science.gov (United States)

    Solomon, P R; Groccia-Ellison, M E

    1996-06-01

    Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

  17. Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

    Directory of Open Access Journals (Sweden)

    Miñarro José

    2010-03-01

    Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

  18. Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

    Science.gov (United States)

    Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

    2010-07-06

    Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

  19. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O, E-mail: shpotyuk@novas.lviv.ua

    2010-11-15

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As{sub x}Se{sub 100-x} (10 {<=} x {<=} 42) and As{sub x}S{sub 100-x} (30 {<=} x {<=} 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As{sub x}S{sub 100-x} within 30 {<=} x < 40 range, while As{sub x}Se{sub 100-x} glasses from the same compositional interval do not show any measurable changes in DSC curves after {gamma}-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of {gamma}-induced excitations within sulfur-based network in comparison with selenium-based one.

  20. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring

  1. Irradiation induced precipitation: a thermodynamical approach

    International Nuclear Information System (INIS)

    Bocquet, J.-L.; Martin, Georges.

    1979-02-01

    A binary alloy (A, B) under steady state irradiation is considered as a ternary alloy (A, B, defects) in constrained equilibrium (the constraint represented by the irradiation consists in maintaining a given supersaturation of point defects). All possible two-body interactions (attractive, repulsive) have been checked between the solvent A, the solute B, and the defects C. The conditions of an irradiation corresponds to a low point-defect concentration; the only cases of interest are those where such a low concentration makes new phases precipitate, which are richer in solute than the initial solid-solution. Radiation induced precipitation is expected to occur under the following necessary conditions: - when the binary alloy (A, B) shows ordering or is ideal, a necessary condition is that the binary solute-defects must show ordering. - when the binary alloy (A, B) shows clustering, a necessary condition is that the temperature must be close to the critical mixing temperature Tsub(AB)sup(D). The physical significance of these conditions is discussed [fr

  2. Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects.

    Science.gov (United States)

    Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

    2016-01-01

    Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m -2 ) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO 2 ), continuously adjusted to reach arterial oxygen saturations (SpO 2 ) of 70-80% for 1 h. IH sessions consisted of 5 min with reduced FiO 2 (SpO 2 = 70-80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results : Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min -1 ) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (-8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH -6 ± 5%, IH -3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (-13 ± 3% vs. -6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in heart

  3. Behaviour of French electrical cables under fire conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, R.; Chaussard, M.; Gonzalez, R.; Lacoue, J.; Mattei, J.M.; Such, J.M

    2001-12-01

    A fire Probabilistic Safety Assessment - called fire PSA - is being carried out by the French Institute of Nuclear Safety and Protection (IPSN) to be used in the framework of the safety assessment of operating 900 MWe PWRs. The aim of this study is to evaluate the core damage conditional probability which could result from a fire. A fire can induce unavailability of safety equipment notably damaging electrical cables that are a significant risk contributor. The purpose of this communication is to present the electrical cable fire tests carried out by IPSN to identify the failure modes and to determine the cable damage criteria. Moreover, are indicated the impact of each kind of cable failure mode and the methodology used to estimate the conditional probability of a failure mode when cable damage occurred. (authors)

  4. Evidence for conjugated linoleic acid-induced embryonic mortality that is independent of egg storage conditions and changes in egg relative fatty acids.

    Science.gov (United States)

    Leone, V A; Stransky, D L; Aydin, R; Cook, M E

    2009-09-01

    Three experiments were performed to determine the effect of conjugated linoleic acid (CLA) on embryonic development in the absence of vitelline membrane disruption. In experiment 1, when eggs from control and CLA (0.5%)-fed hens were stored at 21 or 15 degrees C for 48 h, mineral movement between the yolk and albumen was not observed (with the exception of Mg and Na). Also, it was found that CLA-induced changes in yolk fatty acid content (e.g., increased saturated fatty acids and CLA) had begun to change after 5 d of feeding hens CLA, and no differences were detected in fatty acid composition after 14 d. In experiment 2, the hatchability of eggs incubated directly after oviposition or stored 24 h at 21 or 15 degrees C was determined from hens fed control or 0.5% CLA diets. Regardless of storage conditions, CLA reduced hatchability. These data showed that CLA elicits negative effects on hatchability independent of vitelline membrane disruption or egg storage condition. In experiment 3, eggs were collected from hens fed 0 or 1% CLA daily for 3 wk, stored at 21 degrees C for 24 h, and incubated. Not only did CLA decrease hatchability, the data showed as the days of CLA feeding increased, the days of survival during incubation decreased. Average days of embryonic survival during incubation for the CLA group diminished to 18.0, 13.4, and 6.3 d for wk 1, 2, and 3 of CLA feeding, respectively, and control remained at 20.6, 20.8, and 19.8 for the 3 wk. These studies suggested that without the disruption of the vitelline membrane, hatchability and embryonic days of survival were significantly reduced by maternal CLA feeding in comparison to control-fed hens. Evidence that embryos die earlier the longer the hens are fed CLA, even though no additional changes in the fatty acid content of eggs were found, suggested that factors other than storage and egg yolk fatty acid composition played a role in CLA-induced embryonic mortality.

  5. Heritable effect of plant water availability conditions on restoration of male fertility in the ‘9E’ CMS-inducing cytoplasm of sorghum

    Directory of Open Access Journals (Sweden)

    Lev Aleksandrovich Elkonin

    2012-05-01

    Full Text Available Heritable changes of phenotype arising in plant ontogenesis by the influence of environmental factors belong to the most intriguing genetic phenomena. Studying restoration of male fertility in the ‘9E’ type of CMS-inducing cytoplasm of sorghum and related CMS-inducing cytoplasms, A4 and M35-1A, in some hybrid combinations, we found an unusual inheritance pattern: the Rf-genes functioned in the self-pollinated progenies of F1 hybrids (up to F10 but did not or poorly expressed in backcrosses of these hybrids to CMS-lines with the same cytoplasm type. In experiments on parallel growing of the same F1 hybrid combinations in the ‘dry plot’ and in the ‘irrigated plot’, it was found that high level of plant water availability during panicle and pollen developmental stages significantly increased male fertility of F1 and testcross hybrid populations, in which fertility-restoring genes were in heterozygote state, whereas in F2 populations the influences of water availability conditions cause less pronounce effects. Similarly, male-sterile F1 plants, being transferred from the ‘dry plot’ to greenhouse, produced male-fertile panicles. In addition, male-sterile plants from F2 families, which segregated-out as recessives, being transferred to greenhouse also produced male-fertile panicles. In the progenies of these revertants that were grown in field conditions and in the ‘dry plot’, stable inheritance of male fertility for 3 cycles of self-pollination was observed, and a number of stable fertile lines in the ‘9E’ cytoplasm were obtained. However, in test-crosses of these fertile lines to CMS-lines with the ‘9E’ cytoplasm restoration of male fertility was not observed, except the progeny of one revertant that behaved as fertility-restorer line. These data suggest that the functional state of fertility-restoring genes for the ‘9E’ sorghum cytoplasm is epigenetically-regulated trait established by the influence of environmental

  6. Stress-inducible expression of At DREB1A in transgenic peanut (Arachis hypogaea L.) increases transpiration efficiency under water-limiting conditions.

    Science.gov (United States)

    Bhatnagar-Mathur, Pooja; Devi, M Jyostna; Reddy, D Srinivas; Lavanya, M; Vadez, Vincent; Serraj, R; Yamaguchi-Shinozaki, K; Sharma, Kiran K

    2007-12-01

    Water deficit is the major abiotic constraint affecting crop productivity in peanut (Arachis hypogaea L.). Water use efficiency under drought conditions is thought to be one of the most promising traits to improve and stabilize crop yields under intermittent water deficit. A transcription factor DREB1A from Arabidopsis thaliana, driven by the stress inducible promoter from the rd29A gene, was introduced in a drought-sensitive peanut cultivar JL 24 through Agrobacterium tumefaciens-mediated gene transfer. The stress inducible expression of DREB1A in these transgenic plants did not result in growth retardation or visible phenotypic alterations. T3 progeny of fourteen transgenic events were exposed to progressive soil drying in pot culture. The soil moisture threshold where their transpiration rate begins to decline relative to control well-watered (WW) plants and the number of days needed to deplete the soil water was used to rank the genotypes using the average linkage cluster analysis. Five diverse events were selected from the different clusters and further tested. All the selected transgenic events were able to maintain a transpiration rate equivalent to the WW control in soils dry enough to reduce transpiration rate in wild type JL 24. All transgenic events except one achieved higher transpiration efficiency (TE) under WW conditions and this appeared to be explained by a lower stomatal conductance. Under water limiting conditions, one of the selected transgenic events showed 40% higher TE than the untransformed control.

  7. Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

    Science.gov (United States)

    Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

    2018-08-01

    Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  8. A new calculation method adapted to the experimental conditions for determining samples γ-activities induced by 14 MeV neutrons

    International Nuclear Information System (INIS)

    Rzama, A.; Erramli, H.; Misdaq, M.A.

    1994-01-01

    Induced gamma-activities of different disk shaped irradiated samples and standards with 14 MeV neutrons have been determined by using a Monte Carlo calculation method adapted to the experimental conditions. The self-absorption of the multienergetic emitted gamma rays has been taken into account in the final samples activities. The influence of the different activation parameters has been studied. Na, K, Cl and P contents in biological (red beet) samples have been determined. ((orig.))

  9. Fear Conditioning Downregulates Rac1 Activity in the Basolateral Amygdala Astrocytes to Facilitate the Formation of Fear Memory.

    Science.gov (United States)

    Liao, Zhaohui; Tao, Yezheng; Guo, Xiaomu; Cheng, Deqin; Wang, Feifei; Liu, Xing; Ma, Lan

    2017-01-01

    Astrocytes are well known to scale synaptic structural and functional plasticity, while the role in learning and memory, such as conditioned fear memory, is poorly elucidated. Here, using pharmacological approach, we find that fluorocitrate (FC) significantly inhibits the acquisition of fear memory, suggesting that astrocyte activity is required for fear memory formation. We further demonstrate that fear conditioning downregulates astrocytic Rac1 activity in basolateral amygdala (BLA) in mice and promotes astrocyte structural plasticity. Ablation of astrocytic Rac1 in BLA promotes fear memory acquisition, while overexpression or constitutive activation of astrocytic Rac1 attenuates fear memory acquisition. Furthermore, temporal activation of Rac1 by photoactivatable Rac1 (Rac1-PA) induces structural alterations in astrocytes and in vivo activation of Rac1 in BLA astrocytes during fear conditioning attenuates the formation of fear memory. Taken together, our study demonstrates that fear conditioning-induced suppression of BLA astrocytic Rac1 activity, associated with astrocyte structural plasticity, is required for the formation of conditioned fear memory.

  10. Radiation induced micrencephaly in guinea pigs

    International Nuclear Information System (INIS)

    Wagner, L.K.; Johnston, D.A.; Felleman, D.J.

    1991-01-01

    A brain weight deficit of about 70 mg was induced at doses of approximately 75-mGy and a deficit of 60 mg was induced at 100 mGy. This confirms the effects projected and observed by Wanner and Edwards. Although the data do not demonstrate a clear dose-response relationship between the 75-mGy and 100-mGy groups, the data are statistically consistent with a dose-response effect because of the overlapping confidence intervals. The lack of a statistically significant observation is most likely related to the small difference in doses and the limited numbers of animals examined. There are several factors that can influence the brain weight of guinea pig pups, such as caging and housing conditions, the sex of the animal, and litter size. These should be taken into account for accurate analysis. Dam weight did not appear to have a significant effect. The confirmation of a micrencephalic effect induced x rays at doses of 75-mGy during this late embryonic stage of development is consistent with the findings of small head size induced in those exposed prior to the eight week of conception at Hiroshima. This implies a mechanism for micrencephaly different from those previously suggested and lends credence to a causal relation between radiation and small head size in humans at low doses as reported by Miller and Mulvihill. 16 refs., 13 tabs

  11. Effect of gamma irradiation conditions on the radiation-induced degradation of isobutylene-isoprene rubber

    Energy Technology Data Exchange (ETDEWEB)

    Sen, M. E-mail: msen@hacettepe.edu.tr; Uzun, C.; Kantoglu, Oe.; Erdogan, S.M.; Deniz, V.; Gueven, O

    2003-08-01

    The effect of gamma irradiation conditions on the radiation-induced degradation of uncrosslinked, commercial isobutylene-isoprene rubbers has been investigated in this study. Influence of dose rate and irradiation atmosphere on the degradation of butyl rubber has been followed by viscosimetric and chromatographic analyses. Limiting viscosity number of all butyl rubbers decreased sharply up to 100 kGy and leveled off at around the same molecular weight, independent of dose rate. Slightly higher decrease in viscosity was observed for samples irradiated in air than in nitrogen especially at low dose rate irradiation. Cross-linking G(X), and chain scission G(S) yields of butyl rubbers were calculated by using weight- and number-average molecular weights of irradiated rubber determined by Size Exclusion Chromatography analyses. G-value results showed that chain scission reactions in isobutylene-isoprene rubber in air atmosphere are more favorable than in nitrogen atmosphere, and that lower dose rate enhances chain scission over cross-linking.

  12. PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

    Science.gov (United States)

    Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.

    2012-01-01

    Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30–45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. PMID:22698870

  13. EFFICIENCY EVALUATION OF USING DIFFERENT SPAWNING INDUCERS IN THE CONDITIONS OF ARTIFICIAL REPRODUCTION OF STЕRLET (ACIPENSER RUTHENUS L.

    Directory of Open Access Journals (Sweden)

    V. Kovalenko

    2015-09-01

    Full Text Available Purpose. To study the efficiency of replacing the preparation of sturgeon hypophyses, which is traditional for sturgeon culture but scarce and expensive, with its carp analogue as well as with preparations, which induce own gonadotrophic function of brood sterlet hypophysis when producing offspring in aquaculture conditions. Methodology. The research was performed in the framework of the NULES research theme for 2013–2015, in the conditions of the Fishery Academic, Research and Production Laboratory of the Aquaculture Department (hatching room and fish culture facility with closed water supply in Nemishaev, Borodianka district, Kyiv region. The control in the experiment on a comparative evaluation of the efficiency of different spawning inducers for artificially reproduced sterlet was Reproginol (powder of acetoned sturgeon hypophysis in 50 mg capsules. The experimental variant 1 included acetoned hypophyses of Prussian carp and common carp (no older than a year and half since their collection. The experimental variant 2 is experimental synthetic fish spawning inducer Vadilen-2 (the developer of the preparation is Kovalenko V. O., assistant professor of the Aquaculture Department of the NULES of Ukraine. Collection and processing of experiment data were performed using conventional aquaculture research methods. Findings. It was found that Vadilen-2 produced inducing effect on the gonadotrophic function of sterlet hypophysis and transition from the 4th to the 5th stage of maturation. The effective doses of Vadilen-2 with water temperature of 13–15°C for sterlet females and males were 0.8–1.0 and 0.5–0.6 mg per 1 kg of brood fish, respectively. We observed that sterlet females, which were kept in basins of the recirculated water facility, showed worse results during incubation period when they missed winter period compared to fish, which were kept in the water with natural temperature in the winter. The possibility of replacing the

  14. Blockade of the Naloxone-induced Aversion in Morphine-conditioned Wistar Rats by L-Arginine Intra-central Amygdala

    Directory of Open Access Journals (Sweden)

    Mahnaz Rahimpour

    2011-03-01

    Full Text Available AbstractObjective(sSingle injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence.Materials and MethodsConditioning to morphine (2.5-10 mg/kg, s.c. was established in adult male Wistar rats (weighing 200-250 g using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior to naloxone-paired place conditioning testing.ResultsThe results showed that morphine produced a significant dose-dependent place preference in animals. Naloxone (0.1-0.4 mg/kg, i.p. injections pre-testing of the response to morphine (7.5 mg/kg, s.c. caused a significant aversion at the higher doses (0.4 mg/kg, i.p.. This response was reversed by microinjection of L-arginine (0.3-3 µg/rat, intra-central amygdala prior to naloxone on the day of the testing. The response to L-arginine was blocked by pre-injection of NG-nitro-L-arginine methyl ester (L-NAME (intra-central amygdala.ConclusionA single injection of naloxone on the test day of morphine place conditioning may simply reveal the occurrence of morphine dependence in rats, and that the nitric oxide in the central amygdala most likely plays a key role in this phenomenon.

  15. Octreotide-induced thrombocytopenia: a case report

    Directory of Open Access Journals (Sweden)

    Rizvi Nahid

    2011-07-01

    Full Text Available Abstract Introduction Thrombocytopenia is an extremely rare complication of octreotide therapy and can be life threatening in the setting of esophageal variceal bleeding. We report a case of octreotide-induced reversible thrombocytopenia in a 54-year-old Caucasian man with alcohol-induced cirrhosis and upper gastrointestinal bleeding. Case presentation Our patient's platelet count dropped from 155,000/mm3 upon admission to 77,000/mm3 a few hours after initiation of octreotide therapy and stayed low until the drug's administration was discontinued. Significant recovery was achieved quickly after discontinuation of octreotide. Conclusions Thrombocytopenia is a rare but potentially serious side effect of octreotide therapy and may complicate esophageal variceal bleeding. Physicians should be vigilant in identifying this potentially serious condition.

  16. Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

    Science.gov (United States)

    Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

    2015-04-01

    An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

  17. Cylindrospermopsin induced changes in growth, toxin production and antioxidant response of Acutodesmus acuminatus and Microcystis aeruginosa under differing light and nitrogen conditions.

    Science.gov (United States)

    Chia, Mathias Ahii; Cordeiro-Araújo, Micheline Kézia; Lorenzi, Adriana Sturion; Bittencourt-Oliveira, Maria do Carmo

    2017-08-01

    Growing evidence suggests that some bioactive metabolites (e.g. cyanotoxins) produced by cyanobacteria have allelopathic potential, due to their inhibitory or stimulatory effects on competing species. Although a number of studies have shown that the cyanotoxin cylindrospermopsin (CYN) has variable effects on phytoplankton species, the impact of changing physicochemical conditions on its allelopathic potential is yet to be investigated. We investigated the physiological response of Microcystis aeruginosa (Cyanobacteria) and Acutodesmus acuminatus (Chlorophyta) to CYN under varying nitrogen and light conditions. At 24h, higher microcystins content of M. aeruginosa was recorded under limited light in the presence of CYN, while at 120h the lower levels of the toxins were observed in the presence of CYN under optimum light. Total MCs concentration was significantly (pnitrogen conditions. On the other hand, there were no significant (p>0.05) changes in total MCs concentrations after exposure to CYN under high nitrogen conditions. As expected, limited light and limited nitrogen conditions resulted in lower cell density of both species, while CYN only significantly (pnitrogen condition, the presence of CYN increased internal H 2 O 2 content of both species, which resulted in significant (pnitrogen. These results showed that M. aeruginosa and A. acuminatus have variable response to CYN under changing light and nitrogen conditions, and demonstrate that need to consider changes in physicochemical conditions during ecotoxicological and ecophysiological investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The feasibility of TEA CO2 laser-induced plasma for spectrochemical analysis of geological samples in simulated Martian conditions

    Science.gov (United States)

    Savovic, Jelena; Stoiljkovic, Milovan; Kuzmanovic, Miroslav; Momcilovic, Milos; Ciganovic, Jovan; Rankovic, Dragan; Zivkovic, Sanja; Trtica, Milan

    2016-04-01

    The present work studies the possibility of using pulsed Transversely Excited Atmospheric (TEA) carbon dioxide laser as an energy source for laser-induced breakdown spectroscopy (LIBS) analysis of rocks under simulated Martian atmospheric conditions. Irradiation of a basaltic rock sample with the laser intensity of 56 MW cm- 2, in carbon-dioxide gas at a pressure of 9 mbar, created target plasma with favorable conditions for excitation of all elements usually found in geological samples. Detection limits of minor constituents (Ba, Cr, Cu, Mn, Ni, Sr, V, and Zr) were in the 3 ppm-30 ppm range depending on the element. The precision varied between 5% and 25% for concentration levels of 1% to 10 ppm, respectively. Generally, the proposed relatively simple TEA CO2 laser-LIBS system provides good sensitivity for geological studies under reduced CO2 pressure.

  19. Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

    Science.gov (United States)

    Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel

    2015-08-15

    This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Low-Intensity Repetitive Exercise Induced Rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Mina Tran

    2015-01-01

    Full Text Available Rhabdomyolysis is a rare condition caused by the proteins of damaged muscle cells entering the bloodstream and damaging the kidneys. Common symptoms of rhabdomyolysis are muscle pain and fatigue in conjunction with dark urine; kidney damage is a common symptom among these patients. We present a case of a 23-year-old woman who displayed myalgia in the upper extremities caused by low-intensity and high-repetition exercise. She was successfully diagnosed and treated for exertional rhabdomyolysis. This patient had no significant medical history that would induce this condition. We urge the emergency medical community to observe and monitor patients that complain of myalgia to ensure they are not suffering from rhabdomyolysis even in atypical cases.

  1. Significance of Shrinkage Induced Clamping Pressure in Fiber-Matrix Bonding in Cementitious Composite Materials

    DEFF Research Database (Denmark)

    Stang, Henrik

    1996-01-01

    used in high performance cementitious composite materials.Assuming a Coulomb type of friction on the fiber/matrix interface andusing typical values for the frictional coefficient it is shownthat the shrinkage induced clamping pressure could be one of the mostimportant factors determining the frictional...

  2. Maximum Likelihood Learning of Conditional MTE Distributions

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2009-01-01

    We describe a procedure for inducing conditional densities within the mixtures of truncated exponentials (MTE) framework. We analyse possible conditional MTE specifications and propose a model selection scheme, based on the BIC score, for partitioning the domain of the conditioning variables....... Finally, experimental results demonstrate the applicability of the learning procedure as well as the expressive power of the conditional MTE distribution....

  3. Heat shock protein 72: release and biological significance during exercise.

    Science.gov (United States)

    Whitham, Martin; Fortes, Matthew Benjamin

    2008-01-01

    The cumulative stressors of exercise manifest themselves at a cellular level by threatening the protein homeostasis of the cell. In these conditions, Heat Shock Proteins (HSP) are synthesised to chaperone mis-folded and denatured proteins. As such, the intracellular HSP response is thought to aid cell survival in the face of otherwise lethal cellular stress. Recently, the inducible isoform of the 70 Kda heat shock protein family, Hsp72 has been detected in the extracellular environment. Furthermore, the release of this protein into the circulation has been shown to occur in response to a range of exercise bouts. The present review summarises the current research on the exercise Hsp72 response, the possible mediators and mechanisms of extracellular (e)Hsp72 release, and the possible biological significance of this systemic response. In particular, the possible role of eHsp72 in the modulation of immunity during exercise is discussed.

  4. Identification of significant features by the Global Mean Rank test.

    Science.gov (United States)

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2014-01-01

    With the introduction of omics-technologies such as transcriptomics and proteomics, numerous methods for the reliable identification of significantly regulated features (genes, proteins, etc.) have been developed. Experimental practice requires these tests to successfully deal with conditions such as small numbers of replicates, missing values, non-normally distributed expression levels, and non-identical distributions of features. With the MeanRank test we aimed at developing a test that performs robustly under these conditions, while favorably scaling with the number of replicates. The test proposed here is a global one-sample location test, which is based on the mean ranks across replicates, and internally estimates and controls the false discovery rate. Furthermore, missing data is accounted for without the need of imputation. In extensive simulations comparing MeanRank to other frequently used methods, we found that it performs well with small and large numbers of replicates, feature dependent variance between replicates, and variable regulation across features on simulation data and a recent two-color microarray spike-in dataset. The tests were then used to identify significant changes in the phosphoproteomes of cancer cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two independently published mass spectrometry-based studies. MeanRank outperformed the other global rank-based methods applied in this study. Compared to the popular Significance Analysis of Microarrays and Linear Models for Microarray methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits more consistent behavior regarding the degree of regulation and is robust against the choice of preprocessing methods. MeanRank does not require any imputation of missing values, is easy to understand, and yields results that are easy to interpret. The software implementing the algorithm is freely available for academic and commercial use.

  5. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  6. Anti neuroinflammatory effect of Vildagliptin in ischaemia-reperfusion induced cerebral infarction in normal and STZ induced type-II diabetic rats

    Directory of Open Access Journals (Sweden)

    Kaleru Purnachander

    2016-03-01

    Full Text Available Diabetes is one of the major risk factor for cerebral ischemic stroke. Increased base line levels of oxidative stress in diabetes will lead to cerebral ischemic damage. In pathological conditions such as cerebral ischemia/reperfusion injury, free radicals cause oxidative stress and inflammation leading to increased injury of brain. Inflammation is one of the major pathological mechanisms involved in cerebral ischemia and reperfusion injury. Vildagliptin newer anti-diabetic drug of the class DPP-4 inhibitors is reported to have anti-inflammatory properties apart from its antihyperglycemic activity. Therefore the aim of the present study is to evaluate the anti-inflammatory effect of Vildagliptin against cerebral infarction induced ischemia reperfusion injury in normal and STZ induced diabetic Wistar rats. Cerebral infarction was induced by bilateral common carotid artery occlusion followed by 4 hr reperfusion. Percent infarction, inflammatory markers such as MPO, TNF-α, IL-6 and IL-10 were analysed. Treatment with Vildagliptin for a period of four weeks produced significant reduction in percent cerebral infarct volume. Vildagliptin at 10 mg/kg dose, showed significant reduction in markers like MPO, TNF-α, IL-6 and IL-1β in diabetic group when compared to normal group and in contrast significant increase in anti-inflammatory marker like IL-10 levels. Vildagliptin showed significant cerebroprotective effect by antiinflammatory mechanisms.

  7. Induced Current Characteristics Due to Laser Induced Plasma and Its Application to Laser Processing Monitoring

    International Nuclear Information System (INIS)

    Madjid, Syahrun Nur; Idris, Nasrullah; Kurniawan, Koo Hendrik; Kagawa, Kiichiro

    2011-01-01

    In laser processing, suitable conditions for laser and gas play important role in ensuring a high quality of processing. To determine suitable conditions, we employed the electromagnetic phenomena associated with laser plasma generation. An electrode circuit was utilised to detect induced current due to the fast electrons propelled from the material during laser material processing. The characteristics of induced current were examined by changing parameters such as supplied voltage, laser pulse energy, number of laser shots, and type of ambient gas. These characteristics were compared with the optical emission characteristics. It was shown that the induced current technique proposed in this study is much more sensitive than the optical method in monitoring laser processing, that is to determine the precise focusing condition, and to accurately determine the moment of completion of laser beam penetration. In this study it was also shown that the induced current technique induced by CW CO 2 laser can be applied in industrial material processing for monitoring the penetration completion in a stainless steel plate drilling process.

  8. Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

    Science.gov (United States)

    Bahi, Amine; Dreyer, Jean-Luc

    2013-07-01

    Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Protein patterns of black fungi under simulated Mars-like conditions.

    Science.gov (United States)

    Zakharova, Kristina; Marzban, Gorji; de Vera, Jean-Pierre; Lorek, Andreas; Sterflinger, Katja

    2014-05-29

    Two species of microcolonial fungi - Cryomyces antarcticus and Knufia perforans - and a species of black yeasts-Exophiala jeanselmei - were exposed to thermo-physical Mars-like conditions in the simulation chamber of the German Aerospace Center. In this study the alterations at the protein expression level from various fungi species under Mars-like conditions were analyzed for the first time using 2D gel electrophoresis. Despite of the expectations, the fungi did not express any additional proteins under Mars simulation that could be interpreted as stress induced HSPs. However, up-regulation of some proteins and significant decreasing of protein number were detected within the first 24 hours of the treatment. After 4 and 7 days of the experiment protein spot number was increased again and the protein patterns resemble the protein patterns of biomass from normal conditions. It indicates the recovery of the metabolic activity under Martian environmental conditions after one week of exposure.

  10. Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1987-01-01

    Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intact rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion

  11. Posttraining handling facilitates memory for auditory-cue fear conditioning in rats.

    Science.gov (United States)

    Hui, Isabel R; Hui, Gabriel K; Roozendaal, Benno; McGaugh, James L; Weinberger, Norman M

    2006-09-01

    A large number of studies have indicated that stress exposure or the administration of stress hormones and other neuroactive drugs immediately after a learning experience modulates the consolidation of long-term memory. However, there has been little investigation into how arousal induced by handling of the animals in order to administer these drugs affects memory. Therefore, the present study examined whether the posttraining injection or handling procedure per se affects memory of auditory-cue classical fear conditioning. Male Sprague-Dawley rats, which had been pre-handled on three days for 1 min each prior to conditioning, received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by either a subcutaneous injection of a vehicle solution or brief handling without injection. A control group was placed back into their home cages without receiving any posttraining treatment. Retention was tested 24 h later in a novel chamber and suppression of ongoing motor behavior during a 10-s presentation of the auditory-cue served as the measure of conditioned fear. Animals that received posttraining injection or handling did not differ from each other but showed significantly less stimulus-induced movement compared to the non-handled control group. These findings thus indicate that the posttraining injection or handling procedure is sufficiently arousing or stressful to facilitate memory consolidation of auditory-cue classical fear conditioning.

  12. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Hye Joo Kim

    2012-01-01

    Full Text Available Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria, and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1 cells were cultured under control (14.5 mmol/L mannitol, normoglycemic (NG, 5.5 mmol/L glucose, or hyperglycemic (HG, 20 mmol/L glucose conditions, in the absence or presence of fisetin. Fisetin was added (3–10 μM for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

  13. Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells.

    Science.gov (United States)

    Chen, Pei-Yi; Ho, Yi-Ru; Wu, Ming-Jiuan; Huang, Shun-Ping; Chen, Po-Kong; Tai, Mi-Hsueh; Ho, Chi-Tang; Yen, Jui-Hung

    2015-01-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), a flavonol compound of flavonoids, exhibits a broad spectrum of biological activities including anti-oxidant, anti-inflammatory, anti-cancer and neuroprotective effects. The aim of this study is to investigate the cytoprotective effect of fisetin and the underlying molecular mechanism against hypoxia-induced cell death in PC12 cells. The results of this study showed that fisetin significantly restored the cell viability of PC12 cells under both cobalt chloride (CoCl₂)- and low oxygen-induced hypoxic conditions. Treatment with fisetin successfully reduced the CoCl₂-mediated reactive oxygen species (ROS) production, which was accompanied by an increase in the cell viability of PC12 cells. Furthermore, we found that treatment of PC12 cells with fisetin markedly upregulated hypoxia-inducible factor 1α (HIF-1α), its nuclear accumulation and the hypoxia-response element (HRE)-driven transcriptional activation. The fisetin-mediated cytoprotection during CoCl₂ exposure was significantly attenuated through the administration of HIF-1α siRNA. Moreover, we demonstrated that MAPK/ERK kinase 1/2 (MEK1/2), p38 MAPK and phosphatidylinositol 3-kinase (PI3 K) inhibitors significantly blocked the increase in cell survival that was induced by fisetin treatment under hypoxic conditions. Consistently, increased phosphorylation of ERK, p38 and Akt proteins was observed in PC12 cells treated with fisetin. However, the fisetin-induced HRE-driven transcription was not affected by inhibition of these kinase signaling pathways. Current results reveal for the first time that fisetin promotes cell survival and protects against hypoxia-induced cell death through ROS scavenging and the activation of HIF1α-, MAPK/ERK-, p38 MAPK- and PI3 K/Akt-dependent signaling pathways in PC12 cells.

  14. Clonidine blocks stress-induced craving in cocaine users.

    Science.gov (United States)

    Jobes, Michelle L; Ghitza, Udi E; Epstein, David H; Phillips, Karran A; Heishman, Stephen J; Preston, Kenzie L

    2011-11-01

    Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

  15. The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

    Science.gov (United States)

    Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

    2005-09-01

    We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

  16. Low temperature conditioning of garlic (Allium sativum L.) “seed” cloves induces alterations in sprouts proteome

    Science.gov (United States)

    Dufoo-Hurtado, Miguel D.; Huerta-Ocampo, José Á.; Barrera-Pacheco, Alberto; Barba de la Rosa, Ana P.; Mercado-Silva, Edmundo M.

    2015-01-01

    Low-temperature conditioning of garlic “seed” cloves substitutes the initial climatic requirements of the crop and accelerates the cycle. We have reported that “seed” bulbs from “Coreano” variety conditioned at 5°C for 5 weeks reduces growth and plant weight as well as the crop yields and increases the synthesis of phenolic compounds and anthocyanins. Therefore, this treatment suggests a cold stress. Plant acclimation to stress is associated with deep changes in proteome composition. Since proteins are directly involved in plant stress response, proteomics studies can significantly contribute to unravel the possible relationships between protein abundance and plant stress acclimation. The aim of this work was to study the changes in the protein profiles of garlic “seed” cloves subjected to conditioning at low-temperature using proteomics approach. Two sets of garlic bulbs were used, one set was stored at room temperature (23°C), and the other was conditioned at low temperature (5°C) for 5 weeks. Total soluble proteins were extracted from sprouts of cloves and separated by two-dimensional gel electrophoresis. Protein spots showing statistically significant changes in abundance were analyzed by LC-ESI-MS/MS and identified by database search analysis using the Mascot search engine. The results revealed that low-temperature conditioning of garlic “seed” cloves causes alterations in the accumulation of proteins involved in different physiological processes such as cellular growth, antioxidative/oxidative state, macromolecules transport, protein folding and transcription regulation process. The metabolic pathways affected include protein biosynthesis and quality control system, photosynthesis, photorespiration, energy production, and carbohydrate and nucleotide metabolism. These processes can work cooperatively to establish a new cellular homeostasis that might be related with the physiological and biochemical changes observed in previous studies

  17. Hypoxia-inducible factor 1-alpha up-regulates the expression of phospholipase D2 in colon cancer cells under hypoxic conditions.

    Science.gov (United States)

    Liu, Maoxi; Du, Kunli; Fu, Zhongxue; Zhang, Shouru; Wu, Xingye

    2015-01-01

    Hypoxia is a common characteristic of solid tumors. Recent studies confirmed that phospholipase D2 (PLD2) plays significant roles in cancer progression. In this study, correlation between the expression of PLD2 and the change in the protein level of hypoxia-inducible factor 1-alpha (HIF1-α) was studied. Thirty human colon cancer tissues were examined for the expression of HIF1-α and PLD2 protein, and mRNA levels. SW480 and SW620 cells were exposed to normoxia (20 %) or hypoxia (Hypoxic stress induced PLD2 mRNA and protein expression in SW480 and SW620 cells. Cells transfected with HIF1-α siRNA showed attenuation of hypoxia stress-induced PLD2 expression. In vivo growth decreased in response to HIF1-α and PLD2 inhibition. These results suggest that PLD2 expression in colon cancer cells is up-regulated via HIF1-α in response to hypoxic stress and underscores the crucial role of HIF1-α-induced PLD2 in tumor growth.

  18. Serotonin and conditioning: focus on Pavlovian psychostimulant drug conditioning.

    Science.gov (United States)

    Carey, Robert J; Damianopoulos, Ernest N

    2015-04-01

    Serotonin containing neurons are located in nuclei deep in the brainstem and send axons throughout the central nervous system from the spinal cord to the cerebral cortex. The vast scope of these connections and interactions enable serotonin and serotonin analogs to have profound effects upon sensory/motor processes. In that conditioning represents a neuroplastic process that leads to new sensory/motor connections, it is apparent that the serotonin system has the potential for a critical role in conditioning. In this article we review the basics of conditioning as well as the serotonergic system and point up the number of non-associative ways in which manipulations of serotonin neurotransmission have an impact upon conditioning. We focus upon psychostimulant drug conditioning and review the contribution of drug stimuli in the use of serotonin drugs to investigate drug conditioning and the important impact drug stimuli can have on conditioning by introducing new sensory stimuli that can create or mask a CS. We also review the ways in which experimental manipulations of serotonin can disrupt conditioned behavioral effects but not the associative processes in conditioning. In addition, we propose the use of the recently developed memory re-consolidation model of conditioning as an approach to assess the possible role of serotonin in associative processes without the complexities of performance effects related to serotonin treatment induced alterations in sensory/motor systems. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.

    Science.gov (United States)

    Manwell, Laurie A; Mallet, Paul E

    2015-05-01

    Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA). The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined. Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials. Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses. These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.

  20. Spontaneous pneumomediastinum on CT : related condition and its clinical significance

    International Nuclear Information System (INIS)

    Kim, Sung Hyun; Im, Jung Gi; Seo, Joon Beom; Park, Jae Hyung; Yeon, Kyung Mo; Han, Man Chung

    1998-01-01

    The purpose of this paper is to tabulate underlying disease and to assess the clinical significance of CT-diagnosed spontaneous pneumomediastinum. We retrospectively reviewed CT scans and medical records of 11 consecutive patients with spontaneous pneumomediastinum, and analyzed their clinical history and course, and in five cases, pulmonary function. CT scans of 126 patients with idiopathic pulmonary fibrosis (IPE) collected while the 11 consecutive patients were being treated were analyzed for the prevalence of pneumomediastinum. We analyzed CT findings with respect to the amount and distribution of air in the mediastinum, and the presence of absence of air outside the mediastinum. Spontaneous pneumomediastinum might be associated with idiopathic pulmonary fibrosis and might be a poor prognostic factor in patients with IPE or BOOP. (author). 18 refs., 2 figs

  1. Spontaneous pneumomediastinum on CT : related condition and its clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hyun; Im, Jung Gi; Seo, Joon Beom; Park, Jae Hyung; Yeon, Kyung Mo; Han, Man Chung [Seoul National Univ. (Korea, Republic of). Coll. of Medicine

    1998-03-01

    The purpose of this paper is to tabulate underlying disease and to assess the clinical significance of CT-diagnosed spontaneous pneumomediastinum. We retrospectively reviewed CT scans and medical records of 11 consecutive patients with spontaneous pneumomediastinum, and analyzed their clinical history and course, and in five cases, pulmonary function. CT scans of 126 patients with idiopathic pulmonary fibrosis (IPE) collected while the 11 consecutive patients were being treated were analyzed for the prevalence of pneumomediastinum. We analyzed CT findings with respect to the amount and distribution of air in the mediastinum, and the presence of absence of air outside the mediastinum. Spontaneous pneumomediastinum might be associated with idiopathic pulmonary fibrosis and might be a poor prognostic factor in patients with IPE or BOOP. (author). 18 refs., 2 figs.

  2. A new method to assess Pavlovian conditioning of psychostimulant drug effects.

    Science.gov (United States)

    Damianopoulos, E N; Carey, R J

    1994-07-01

    Experimental studies of psychoactive drugs by pavlovian drug-conditioning methods, which originally began with investigations of drug-induced responses mediated by the autonomic nervous system, have now been expanded to include drug-induced response effects expressed as modulations of spontaneous motoric behaviors. In the latter application, however, equivalent behavioral response outcomes in post-treatment tests for conditioning can occur following a psychostimulant drug treatment either through drug interference effects on habituation processes, drug-induced stress effects and/or by pavlovian conditioning of the drug-induced motoric activation effect. Current methodologies for the study of pavlovian conditioned drug effects and/or drug sensitization cannot distinguish among these possibilities. This methodological inadequacy was addressed by a modification of the conventional paired-unpaired treatment protocol. In the new protocol, the animal is sequentially placed into two test compartments with the drug treatment administered in conjunction with placement into the second test compartment. This design permits a differentiation of a pavlovian conditioned drug responses from non-conditioned drug effects through continuous measurement of the non-drug behavioral baseline in both the drug and non-drug control treatment groups combined with multiple response measurements and post-treatment tests for conditioning at variable post-conditioning intervals. The present study details the use of the new modified pavlovian protocol with repeated cocaine (10 mg/kg) treatment. A cocaine conditioned response at 1, 7, and 21 days post-conditioning was identified and distinguished from habituation and stress effects.

  3. Beam-Induced Damage Mechanisms and their Calculation

    CERN Document Server

    Bertarelli, A

    2016-01-01

    The rapid interaction of highly energetic particle beams with matter induces dynamic responses in the impacted component. If the beam pulse is sufficiently intense, extreme conditions can be reached, such as very high pressures, changes of material density, phase transitions, intense stress waves, material fragmentation and explosions. Even at lower intensities and longer time-scales, significant effects may be induced, such as vibrations, large oscillations, and permanent deformation of the impacted components. These lectures provide an introduction to the mechanisms that govern the thermomechanical phenomena induced by the interaction between particle beams and solids and to the analytical and numerical methods that are available for assessing the response of impacted components. An overview of the design principles of such devices is also provided, along with descriptions of material selection guidelines and the experimental tests that are required to validate materials and components exposed to interactio...

  4. Comparison of wavefront aberrations under cycloplegic, scotopic and photopic conditions using WaveScan

    Directory of Open Access Journals (Sweden)

    Rong Fan

    2012-04-01

    Full Text Available PURPOSE: To evaluate the differences of wavefront aberrations under cycloplegic, scotopic and photopic conditions. METHODS: A total of 174 eyes of 105 patients were measured using the wavefront sensor (WaveScan® 3.62 under different pupil conditions: cycloplegic 8.58 ± 0.54 mm (6.4 mm - 9.5 mm, scotopic 7.53 ± 0.69 mm (5.7 mm - 9.1 mm and photopic 6.08 ± 1.14 mm (4.1 mm - 8.8 mm. The pupil diameter, standard Zernike coefficients, root mean square of higher-order aberrations and dominant aberrations were compared between cycloplegic and scotopic conditions, and between scotopic and photopic conditions. RESULTS: The pupil diameter was 7.53 ± 0.69 mm under the scotopic condition, which reached the requirement of about 6.5 mm optical zone design in the wavefront-guided surgery and prevented measurement error due to the pupil centroid shift caused by mydriatics. Pharmacological pupil dilation induced increase of standard Zernike coefficients Z3-3, Z4(0 and Z5-5. The higher-order aberrations, third-order aberration, fourth-order aberration, fifth-order aberration, sixth-order aberration, and spherical aberration increased statistically significantly, compared to the scotopic condition (P<0.010. When the scotopic condition shifted to the photopic condition, the standard Zernike coefficients Z4(0, Z4², Z6-4, Z6-2, Z6² decreased and all the higher-order aberrations decreased statistically significantly (P<0.010, demonstrating that accommodative miosis can significantly improve vision under the photopic condition. Under the three conditions, the vertical coma aberration appears the most frequently within the dominant aberrations without significant effect by pupil size variance, and the proportion of spherical aberrations decreased with the decrease of the pupil size. CONCLUSIONS: The wavefront aberrations are significantly different under cycloplegic, scotopic and photopic conditions. Using the wavefront sensor (VISX WaveScan to measure scotopic

  5. Adherence to abiotic surface induces SOS response in Escherichia coli K-12 strains under aerobic and anaerobic conditions.

    Science.gov (United States)

    Costa, Suelen B; Campos, Ana Carolina C; Pereira, Ana Claudia M; de Mattos-Guaraldi, Ana Luiza; Júnior, Raphael Hirata; Rosa, Ana Cláudia P; Asad, Lídia M B O

    2014-09-01

    During the colonization of surfaces, Escherichia coli bacteria often encounter DNA-damaging agents and these agents can induce several defence mechanisms. Base excision repair (BER) is dedicated to the repair of oxidative DNA damage caused by reactive oxygen species (ROS) generated by chemical and physical agents or by metabolism. In this work, we have evaluated whether the interaction with an abiotic surface by mutants derived from E. coli K-12 deficient in some enzymes that are part of BER causes DNA damage and associated filamentation. Moreover, we studied the role of endonuclease V (nfi gene; 1506 mutant strain) in biofilm formation. Endonuclease V is an enzyme that is involved in DNA repair of nitrosative lesions. We verified that endonuclease V is involved in biofilm formation. Our results showed more filamentation in the xthA mutant (BW9091) and triple xthA nfo nth mutant (BW535) than in the wild-type strain (AB1157). By contrast, the mutant nfi did not present filamentation in biofilm, although its wild-type strain (1466) showed rare filaments in biofilm. The filamentation of bacterial cells attaching to a surface was a consequence of SOS induction measured by the SOS chromotest. However, biofilm formation depended on the ability of the bacteria to induce the SOS response since the mutant lexA Ind(-) did not induce the SOS response and did not form any biofilm. Oxygen tension was an important factor for the interaction of the BER mutants, since these mutants exhibited decreased quantitative adherence under anaerobic conditions. However, our results showed that the presence or absence of oxygen did not affect the viability of BW9091 and BW535 strains. The nfi mutant and its wild-type did not exhibit decreased biofilm formation under anaerobic conditions. Scanning electron microscopy was also performed on the E. coli K-12 strains that had adhered to the glass, and we observed the presence of a structure similar to an extracellular matrix that depended on the

  6. Effect of ASF (a Compound of Traditional Chinese Medicine on Behavioral Sensitization Induced by Ethanol and Conditioned Place Preference in Mice

    Directory of Open Access Journals (Sweden)

    Da-chao Wen

    2014-01-01

    Full Text Available ASF composed by semen and epimedium herbal is a traditional plant compound that is widely used in the treatment of insomnia. Studies have shown that saponins and flavonoids contained in semen can significantly decrease the content of excitatory neurotransmitter Glu in mice. And the total flavone of YinYangHuo can increase the release of GABA in the anterior periventricular system of rat and increase the affinity of GABA for the receptors GABAA. It can be inferred that their synergism may have effect on the neurotransmitter that causes behavioral sensitization and conditioned place preference in experimental animals and affects their drinking behaviors, which is the starting point of this research. The present study found that ASF can inhibit development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. We demonstrate the inhibition of ASF on behavioral sensitization partly due to its effect on the mesolimbic neurotransmitter system, including decreasing level of DA and Glu and increasing the content of GABA. It suggested that the ASF may have pharmacological effects in the treatment of alcohol addiction.

  7. Virtual hand illusion induced by visuomotor correlations.

    Directory of Open Access Journals (Sweden)

    Maria V Sanchez-Vives

    Full Text Available BACKGROUND: Our body schema gives the subjective impression of being highly stable. However, a number of easily-evoked illusions illustrate its remarkable malleability. In the rubber-hand illusion, illusory ownership of a rubber-hand is evoked by synchronous visual and tactile stimulation on a visible rubber arm and on the hidden real arm. Ownership is concurrent with a proprioceptive illusion of displacement of the arm position towards the fake arm. We have previously shown that this illusion of ownership plus the proprioceptive displacement also occurs towards a virtual 3D projection of an arm when the appropriate synchronous visuotactile stimulation is provided. Our objective here was to explore whether these illusions (ownership and proprioceptive displacement can be induced by only synchronous visuomotor stimulation, in the absence of tactile stimulation. METHODOLOGY/PRINCIPAL FINDINGS: To achieve this we used a data-glove that uses sensors transmitting the positions of fingers to a virtually projected hand in the synchronous but not in the asynchronous condition. The illusion of ownership was measured by means of questionnaires. Questions related to ownership gave significantly larger values for the synchronous than for the asynchronous condition. Proprioceptive displacement provided an objective measure of the illusion and had a median value of 3.5 cm difference between the synchronous and asynchronous conditions. In addition, the correlation between the feeling of ownership of the virtual arm and the size of the drift was significant. CONCLUSIONS/SIGNIFICANCE: We conclude that synchrony between visual and proprioceptive information along with motor activity is able to induce an illusion of ownership over a virtual arm. This has implications regarding the brain mechanisms underlying body ownership as well as the use of virtual bodies in therapies and rehabilitation.

  8. Clinical significance of changes of plasma endothelin vasoactive factors (ET and NO) as well as serum related interleukin (IL-6 and IL-8) levels in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Chen Ying

    2009-01-01

    Objective: To investigate the clinical etiological significance of changes of plasma endothelin (ET) and nitric oxide (NO) as well as serum interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in patients with pregnancy induced hypertension. Methods: Plasma ET (with RIA), NO (with biochemistry) and serum IL-6, IL-8 (with RIA) levels were measured in 32 pregnant women with PIH, 35 normal pregnant women without PIH and 35 non-pregnant women (as controls). Results: The plasma ET, NO level were significantly higher in normal pregnant women than those in the non-pregnant women controls, while serum levels of IL-6 and IL-8 levels were only slightly higher without significance (P>0.05). Before treatment, the blood ET, IL-6 and IL- 8 levels were significantly higher in patients with pregnancy induced hypertension than those in the control (P<0.01), while plasma levels of NO were significantly decreased (P<0.01), Two weeks after treatment, the plasma ET, NO and serum IL-6 and IL-8 levels were markedly corrected with no significantly differences from those in controls. The ET levels and serum IL-6, IL-8 levels were mutually positively correlated (r=0.6097, 0.7213, P<0.01). Conclusion: Determination of changes of plasma ET and NO, serum IL-6 and IL-8 levels in patients with pregnancy induced hypertension was helpful for outcome prediction. (authors)

  9. Recovery from swimming-induced hypothermia in king penguins: effects of nutritional condition.

    Science.gov (United States)

    Halsey, L G; Handrich, Y; Rey, B; Fahlman, A; Woakes, A J; Butler, P J

    2008-01-01

    We investigated changes in the rate of oxygen consumption (V O2) and body temperature of wild king penguins (Aptenodytes patagonicus) in different nutritional conditions during recovery after exposure to cold water. Over time, birds undertook an identical experiment three times, each characterized by different nutritional conditions: (1) having recently completed a foraging trip, (2) after fasting for many days, and (3) having been refed one meal after the fast. The experiments consisted of a 2-h session in a water channel followed by a period of recovery in a respirometer chamber on land. Refed birds recovered significantly more quickly than fed birds, in terms of both time to reach resting V O2 on land and time to reach recovery of lower abdominal temperature. Previous work found that when penguins are in cold water, abdominal temperatures decrease less in refed birds than in fed or fasted birds, suggesting that refed birds may be vasoconstricting the periphery while perfusing the gut region to access nutrients. This, alongside an increased resting [V O2], seems the most reasonable explanation for why refed birds recovered more quickly subsequent to cold-water exposure in this study; that is, vasoconstriction of the insulative periphery meant that they lost less heat generated by the body core.

  10. A procedure to observe context-induced renewal of pavlovian-conditioned alcohol-seeking behavior in rats.

    Science.gov (United States)

    Maddux, Jean-Marie; Lacroix, Franca; Chaudhri, Nadia

    2014-09-19

    Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

  11. Reporting instructions significantly impact false positive rates when reading chest radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J. [The University of Sydney, Medical Image Optimisation and Perception Group, Discipline of Medical Radiation Sciences, Faculty of Health Sciences, Lidcombe, NSW (Australia)

    2016-10-15

    To determine the impact of specific reporting tasks on the performance of radiologists when reading chest radiographs. Ten experienced radiologists read a set of 40 postero-anterior (PA) chest radiographs: 21 nodule free and 19 with a proven solitary nodule. There were two reporting conditions: an unframed task (UFT) to report any abnormality and a framed task (FT) reporting only lung nodule/s. Jackknife free-response operating characteristic (JAFROC) figure of merit (FOM), specificity, location sensitivity and number of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) decisions were used for analysis. JAFROC FOM for tasks showed a significant reduction in performance for framed tasks (P = 0.006) and an associated decrease in specificity (P = 0.011) but no alteration to the location sensitivity score. There was a significant increase in number of FP decisions made during framed versus unframed tasks for nodule-containing (P = 0.005) and nodule-free (P = 0.011) chest radiographs. No significant differences in TP were recorded. Radiologists report more FP decisions when given specific reporting instructions to search for nodules on chest radiographs. The relevance of clinical history supplied to radiologists is called into question and may induce a negative effect. (orig.)

  12. Reporting instructions significantly impact false positive rates when reading chest radiographs

    International Nuclear Information System (INIS)

    Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J.

    2016-01-01

    To determine the impact of specific reporting tasks on the performance of radiologists when reading chest radiographs. Ten experienced radiologists read a set of 40 postero-anterior (PA) chest radiographs: 21 nodule free and 19 with a proven solitary nodule. There were two reporting conditions: an unframed task (UFT) to report any abnormality and a framed task (FT) reporting only lung nodule/s. Jackknife free-response operating characteristic (JAFROC) figure of merit (FOM), specificity, location sensitivity and number of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) decisions were used for analysis. JAFROC FOM for tasks showed a significant reduction in performance for framed tasks (P = 0.006) and an associated decrease in specificity (P = 0.011) but no alteration to the location sensitivity score. There was a significant increase in number of FP decisions made during framed versus unframed tasks for nodule-containing (P = 0.005) and nodule-free (P = 0.011) chest radiographs. No significant differences in TP were recorded. Radiologists report more FP decisions when given specific reporting instructions to search for nodules on chest radiographs. The relevance of clinical history supplied to radiologists is called into question and may induce a negative effect. (orig.)

  13. Conditional deletion of Hdac3 in osteoprogenitor cells attenuates diet-induced systemic metabolic dysfunction

    Science.gov (United States)

    McGee-Lawrence, Meghan E.; White, Thomas A.; LeBrasseur, Nathan K.; Westendorf, Jennifer J.

    2015-01-01

    Obesity is a major health epidemic in the United States and a leading cause of preventable diseases including type 2 diabetes. A growing body of evidence indicates that the skeleton influences whole body metabolism and suggests a new avenue for developing novel therapeutic agents, but the underlying mechanisms are not well understood. Here, it is demonstrated that conditional deletion of an epigenetic regulator, Hdac3, in osteoblast progenitor cells abrogates high fat diet-induced insulin resistance and hepatic steatosis. These Hdac3-deficient mice have reduced bone formation and lower circulating levels of total and undercarboxylated osteocalcin, coupled with decreased bone resorption activity. They also maintain lower body fat and fasting glucose levels on normal and high fat chow diets. The mechanisms by which Hdac3 controls systemic energy homeostasis from within osteoblasts have not yet been fully realized, but the current study suggests that it does not involve elevated levels of circulating osteocalcin. Thus, Hdac3 is a new player in the emerging paradigm that the skeleton influences systemic energy metabolism. PMID:25666992

  14. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

    Science.gov (United States)

    Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2015-08-01

    Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

  15. Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

    Science.gov (United States)

    Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

    2006-04-01

    Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

  16. Spinal Stiffness in Prone and Upright Postures During 0-1.8 g Induced by Parabolic Flight.

    Science.gov (United States)

    Swanenburg, Jaap; Meier, Michael L; Langenfeld, Anke; Schweinhardt, Petra; Humphreys, B Kim

    2018-06-01

    The purpose of this study was to analyze posterior-to-anterior spinal stiffness in Earth, hyper-, and microgravity conditions during both prone and upright postures. During parabolic flight, the spinal stiffness of the L3 vertebra of a healthy 37-yr-old man was measured in normal Earth gravity (1.0 g), hypergravity (1.8 g), and microgravity (0.0 g) conditions induced in the prone and upright positions. Differences in spinal stiffness were significant across all three gravity conditions in the prone and upright positions. Most effect sizes were large; however, in the upright posture, the effect size between Earth gravity and microgravity was medium. Significant differences in spinal stiffness between the prone and upright positions were found during Earth gravity and hypergravity conditions. No difference was found between the two postures during microgravity conditions. Based on repeated measurements of a single individual, our results showed detectable changes in posterior-to-anterior spinal stiffness. Spinal stiffness increased during microgravity and decreased during hypergravity conditions. In microgravity conditions, posture did not impact spinal stiffness. More data on spinal stiffness in variable gravitational conditions is needed to confirm these results.Swanenburg J, Meier ML, Langenfeld A, Schweinhardt P, Humphreys BK. Spinal stiffness in prone and upright postures during 0-1.8 g induced by parabolic flight. Aerosp Med Hum Perform. 2018; 89(6):563-567.

  17. Bicarbonate trigger for inducing lipid accumulation in algal systems

    Science.gov (United States)

    Gardner, Robert; Peyton, Brent; Cooksey, Keith E.

    2015-08-04

    The present invention provides bicarbonate containing and/or bicarbonate-producing compositions and methods to induce lipid accumulation in an algae growth system, wherein the algae growth system is under light-dark cycling condition. By adding said compositions at a specific growth stage, said methods lead to much higher lipid accumulation and/or significantly reduced total time required for accumulating lipid in the algae growth system.

  18. Wearable Vibrotactile Biofeedback Device Allowing Identification of Different Floor Conditions for Lower-Limb Amputees.

    Science.gov (United States)

    Wan, Anson H; Wong, Duo W; Ma, Christina Z; Zhang, Ming; Lee, Winson C

    2016-07-01

    To evaluate a newly developed biofeedback device enabling lower-limb amputees to identify various floor conditions. Self-control with repeated measures (with and without the biofeedback device) within the amputee group, and group control comparing between amputee and nonamputee groups. University locomotion laboratory. Five lower-limb amputees and 8 nonamputees (N=13). A wearable biofeedback device, which identified different floor conditions by analyzing the force patterns under the prosthetic feet and provided vibration cues in response to different floor conditions, was provided to the amputees. The subjects stepped on a foam platform concealing a small object or no object at 1 of the 4 locations of the foot sole. Subjects were asked whether there was a small object under their feet and the location of the object if it existed. The test was repeated with 4 different object types and 4 object locations. The success rate of floor identification was evaluated. Without the biofeedback device, nonamputee subjects (76.56%) identified floor conditions better than amputees (22.5%) significantly (Pdevice, the amputees significantly improved (Pdevice, amputees significantly improved their abilities in identifying different floor conditions. Future attempts could configure the device to allow it to provide warning signals in response to fall-inducing conditions. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. β-N-oxalyl-L-α, β- diaminopropionic acid induces HRE expression by inhibiting HIF-prolyl hydroxylase-2 in normoxic conditions.

    Science.gov (United States)

    Eslavath, Ravi Kumar; Sharma, Deepshikha; Bin Omar, Nabil A M; Chikati, Rajasekhar; Teli, Mahesh Kumar; Rajanikant, G K; Singh, Surya S

    2016-11-15

    Hypoxia inducible factor (HIF)-1α, a subunit of HIF transcription factor, regulates cellular response to hypoxia. In normoxic conditions, it is hydroxylated by prolyl hydroxylase (PHD)-2 and targeted for proteosomal degradation. Drugs which inhibit PHD-2 have implications in conditions arising from insufficient blood supply. β-ODAP (β-N- oxalyl-L-α, β- diaminopropionic acid), a non-protein excitatory amino acid present in Lathyrus sativus, is an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor agonist known to activate conventional protein kinase C and stabilize HIF-1α under normoxic conditions. However, the mechanism of HIF-1α stabilization by this compound is unknown. In silico approach was used to understand the mechanism of stabilization of HIF-1α which revealed β-ODAP interacts with key amino acid residues and Fe 2+ at the catalytic site of PHD-2. These results were further corroborated with luciferase HRE (hypoxia response element) reporter system in HeLa cells. Different chemical modulators of PHD-2 activity and HIF-1α levels were included in the study for comparison. Results obtained indicate that β-ODAP inhibits PHD-2 and facilitates HIF dependent HRE expression and hence, might be helpful in conditions arising from hypoxia. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Erythroid differentiation and commitment in rat erythroleukemia cells with hypertonic culture conditions.

    OpenAIRE

    Yamaguchi, Y; Kluge, N; Ostertag, W; Furusawa, M

    1981-01-01

    Cell cultures of 7,12-dimethylbenz[a]anthracene-induced rat erythroleukemia can be stimulated to synthesize hemoglobin when cultured in hypertonic media. During hypertonic treatment the intracellular osmotic conditions immediately readjust to those of the extracellular medium. None of the Friend virus-induced mouse erythroleukemia cell lines was inducible for differentiation with the same hypertonic culture conditions used for rat cells. Earliest commitment to erythroid terminal differentiati...

  1. Evaluation of viewing experiences induced by a curved three-dimensional display

    Science.gov (United States)

    Mun, Sungchul; Park, Min-Chul; Yano, Sumio

    2015-10-01

    Despite an increased need for three-dimensional (3-D) functionality in curved displays, comparisons pertinent to human factors between curved and flat panel 3-D displays have rarely been tested. This study compared stereoscopic 3-D viewing experiences induced by a curved display with those of a flat panel display by evaluating subjective and objective measures. Twenty-four participants took part in the experiments and viewed 3-D content with two different displays (flat and curved 3-D display) within a counterbalanced and within-subject design. For the 30-min viewing condition, a paired t-test showed significantly reduced P300 amplitudes, which were caused by engagement rather than cognitive fatigue, in the curved 3-D viewing condition compared to the flat 3-D viewing condition at P3 and P4. No significant differences in P300 amplitudes were observed for 60-min viewing. Subjective ratings of realness and engagement were also significantly higher in the curved 3-D viewing condition than in the flat 3-D viewing condition for 30-min viewing. Our findings support that curved 3-D displays can be effective for enhancing engagement among viewers based on specific viewing times and environments.

  2. Dissolution Coupled Biodegradation of Pce by Inducing In-Situ Biosurfactant Production Under Anaerobic Conditions

    Science.gov (United States)

    Dominic, J.; Nambi, I. M.

    2013-12-01

    Biosurfactants have proven to enhance the bioavailability and thereby elevate the rate of degradation of Light Non Aqueous Phase Liquids (LNAPLs) such as crude oil and petroleum derivatives. In spite of their superior characteristics, use of these biomolecules for remediation of Dense Non Aqueous Phase Liquids (DNAPLs) such as chlorinated solvents is still not clearly understood. In this present study, we have investigated the fate of tetrachloroethylene (PCE) by inducing in-situ biosurfactants production, a sustainable option which hypothesizes increase in bioavailability of LNAPLs. In order to understand the effect of biosurfactants on dissolution and biodegradation under the inducement of in-situ biosurfactant production, batch experiments were conducted in pure liquid media. The individual influence of each process such as biosurfactant production, dissolution of PCE and biodegradation of PCE were studied separately for getting insights on the synergistic effect of each process on the fate of PCE. Finally the dissolution coupled biodegradation of non aqueous phase PCE was studied in conditions where biosurfactant production was induced by nitrate limitation. The effect of biosurfactants was differentiated by repeating the same experiments were the biosurfactant production was retarded. The overall effect of in-situ biosurfactant production process was evaluated by use of a mathematical model. The process of microbial growth, biosurfactant production, dissolution and biodegradation of PCE were translated as ordinary differential equations. The modelling exercise was mainly performed to get insight on the combined effects of various processes that determine the concentration of PCE in its aqueous and non-aqueous phases. Model simulated profiles of PCE with the kinetic coefficients evaluated earlier from individual experiments were compared with parameters fitted for observations in experiments with dissolution coupled biodegradation process using optimization

  3. Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration.

    Science.gov (United States)

    Blacktop, Jordan M; Todd, Ryan P; Sorg, Barbara A

    2017-05-15

    Addiction involves drug-induced neuroplasticity in the circuitry of motivated behavior, which includes the medial forebrain bundle and the lateral hypothalamic area. Emerging at the forefront of neuroplasticity regulation are specialized extracellular matrix (ECM) structures that form perineuronal nets (PNNs) around certain neurons, mainly parvalbumin positive (PV + ), fast-spiking interneurons (FSINs), making them a promising target for the regulation of drug-induced neuroplasticity. Despite the emerging significance of PNNs in drug-induced neuroplasticity and the well-established role of the lateral hypothalamic area (LHA) in reward, reinforcement, and motivation, very little is known about how PNN-expressing neurons control drug-seeking behavior. We found that a discrete region of the anterior dorsal LHA (LHAad) exhibited robust PNN and dense ECM expression. Approximately 87% of parvalbumin positive (PV + ) neurons co-expressed the PNN marker Wisteria floribunda agglutinin (WFA), while 62% of WFA positive (WFA + ) neurons co-expressed PV in the LHAad of drug naïve rats. Removal of PNNs within this brain region via chrondroitinase ABC (Ch-ABC) administration abolished acquisition of cocaine-induced CPP and significantly attenuated the acquisition of cocaine self-administration (SA). Removal of LHAad PNNs did not affect locomotor activity, sucrose intake, sucrose-induced CPP, or acquisition of sucrose SA in separate groups of cocaine naïve animals. These data suggest that PNN-dependent neuroplasticity within the LHAad is critical for the acquisition of both cocaine-induced CPP and SA but is not general to all rewards, and that PNN degradation may have utility for the management of drug-associated behavioral plasticity and memory in cocaine addicts. Published by Elsevier Ltd.

  4. Fear Conditioning Effects on Sensitivity to Drug Reward

    Science.gov (United States)

    2010-06-01

    motivational responses and self-administration behaviors (Robbins et al., 2008). Pavlovian conditioning mechanisms link unconditioned drug responses...model. Induction of fear conditioning is followed by measurement of sensitivity to drug reward using a conditioned place preference (CPP) model to...morphine. Conditioned drug reward is a relevant model in addiction because environmental cues (e.g. a barroom) induce craving and persistent

  5. Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis.

    Science.gov (United States)

    Robinson, Ainsley M; Sakkal, Samy; Park, Anthony; Jovanovska, Valentina; Payne, Natalie; Carbone, Simona E; Miller, Sarah; Bornstein, Joel C; Bernard, Claude; Boyd, Richard; Nurgali, Kulmira

    2014-12-01

    Damage to the enteric nervous system (ENS) associated with intestinal inflammation may underlie persistent alterations to gut functions, suggesting that enteric neurons are viable targets for novel therapies. Mesenchymal stem cells (MSCs) offer therapeutic benefits for attenuation of neurodegenerative diseases by homing to areas of inflammation and exhibiting neuroprotective, anti-inflammatory, and immunomodulatory properties. In culture, MSCs release soluble bioactive factors promoting neuronal survival and suppressing inflammation suggesting that MSC-conditioned medium (CM) provides essential factors to repair damaged tissues. We investigated whether MSC and CM treatments administered by enema attenuate 2,4,6-trinitrobenzene-sulfonic acid (TNBS)-induced enteric neuropathy and motility dysfunction in the guinea pig colon. Guinea pigs were randomly assigned to experimental groups and received a single application of TNBS (30 mg/kg) followed by 1 × 10(6) human bone marrow-derived MSCs, 300 μl CM, or 300 μl unconditioned medium 3 h later. After 7 days, the effect of these treatments on enteric neurons was assessed by histological, immunohistochemical, and motility analyses. MSC and CM treatments prevented inflammation-associated weight loss and gross morphological damage in the colon; decreased the quantity of immune infiltrate in the colonic wall (P ChAT, and nNOS immunoreactivity (P < 0.05); and alleviated inflammation-induced colonic dysmotility (contraction speed; P < 0.001, contractions/min; P < 0.05). These results provide strong evidence that both MSC and CM treatments can effectively prevent damage to the ENS and alleviate gut dysfunction caused by TNBS-induced colitis. Copyright © 2014 the American Physiological Society.

  6. Mixotrophic transition induced lipid productivity in Chlorella pyrenoidosa under stress conditions for biodiesel production

    Directory of Open Access Journals (Sweden)

    Hari Prasad Ratnapuram

    2018-01-01

    Full Text Available Influence of mixotrophic mode and its transition to various trophic modes under stress conditions was assessed during two stage cultivation of Chlorella pyrenoidosa. Significant lipid productivity was triggered under low light intensity, glucose + bicarbonate supplementation and nitrogen starvation. The association between biomass and lipid productivity, fatty acid composition during mixotrophic transition was critically evaluated. Biomass in growth phase (GP and stress phase (SP was 6.14 g/l and 5.14 g/l, respectively, in mixotrophic mode. Higher lipid productivity of 284 g/kg and 154.3 g/kg of neutral lipids was achieved in SP in mixotrophic-mixotrophic (MM and mixotrophic-heterotrophic (MH modes, respectively. Stress conditions resulted in high unsaturated fatty acid methyl esters in MH mode. In addition, neutral lipid content was 58% in MH and 52% in MM, that can be attributed to carbon source that is supplemented even in stress phase. Exploring such novel strategies can generate sustainable avenues for biodiesel production.

  7. Task-induced frequency modulation features for brain-computer interfacing

    Science.gov (United States)

    Jayaram, Vinay; Hohmann, Matthias; Just, Jennifer; Schölkopf, Bernhard; Grosse-Wentrup, Moritz

    2017-10-01

    Objective. Task-induced amplitude modulation of neural oscillations is routinely used in brain-computer interfaces (BCIs) for decoding subjects’ intents, and underlies some of the most robust and common methods in the field, such as common spatial patterns and Riemannian geometry. While there has been some interest in phase-related features for classification, both techniques usually presuppose that the frequencies of neural oscillations remain stable across various tasks. We investigate here whether features based on task-induced modulation of the frequency of neural oscillations enable decoding of subjects’ intents with an accuracy comparable to task-induced amplitude modulation. Approach. We compare cross-validated classification accuracies using the amplitude and frequency modulated features, as well as a joint feature space, across subjects in various paradigms and pre-processing conditions. We show results with a motor imagery task, a cognitive task, and also preliminary results in patients with amyotrophic lateral sclerosis (ALS), as well as using common spatial patterns and Laplacian filtering. Main results. The frequency features alone do not significantly out-perform traditional amplitude modulation features, and in some cases perform significantly worse. However, across both tasks and pre-processing in healthy subjects the joint space significantly out-performs either the frequency or amplitude features alone. This result only does not hold for ALS patients, for whom the dataset is of insufficient size to draw any statistically significant conclusions. Significance. Task-induced frequency modulation is robust and straight forward to compute, and increases performance when added to standard amplitude modulation features across paradigms. This allows more information to be extracted from the EEG signal cheaply and can be used throughout the field of BCIs.

  8. Generic conditions for suppressing the coherent synchrotron radiation induced emittance growth in a two-dipole achromat

    Science.gov (United States)

    Jiao, Yi; Cui, Xiaohao; Huang, Xiyang; Xu, Gang

    2014-06-01

    The effect of the coherent synchrotron radiation (CSR) becomes evident, and leads to increased beam energy spread and transverse emittance dilution, as both the emittance and bunch length of the electron beams are continuously pushed down in present and forthcoming high-brightness light sources and linear colliders. Suppressing this effect is important to preserve the expected machine performance. Methods of the R-matrix analysis and the Courant-Snyder formalism analysis have been proposed to evaluate and to suppress the emittance growth due to CSR in achromatic cells. In this paper a few important modifications are made on these two methods, which enable us to prove that these two methods are equivalent to each other. With the modified analysis, we obtain explicit and generic conditions of cancelling the CSR-driven emittance excitation in a single achromat consisting of two dipoles of arbitrary bending angles. In spite of the fact that the analysis constrains itself in a linear regime, based on the assumption that CSR-induced particle energy deviation is proportional to both θ and ρ1/3, with θ being the bending angle and ρ the bending radius, it is demonstrated through ELEGANT simulations that the conditions derived from this analysis are still effective in suppressing the emittance growth when a more detailed one-dimensional CSR model is considered. In addition, it illustrates that the emittance growth can be reduced to a lower level with the proposed conditions than with the other two approaches, such as matching the beam envelope to the CSR kick and setting the cell-to-cell betatron phase advance to an appropriate value.

  9. Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Celine J. Granier

    2014-08-01

    Full Text Available PDCD2 (programmed cell death domain 2 is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in mammalian development, we have examined PDCD2 activity in mouse blastocyst embryos, as well as in mouse embryonic stem cells (ESCs and embryonic fibroblasts (MEFs. We have studied mice bearing a targeted PDCD2 locus functioning as a null allele through a splicing gene trap, or as a conditional knockout, by deletion of exon2 containing the MYND domain. Tamoxifen-induced knockout of PDCD2 in MEFs, as well as in ESCs, leads to defects in progression from the G1 to the S phase of cell cycle, associated with increased levels of p53 protein and p53 target genes. G1 prolongation in ESCs was not associated with induction of differentiation. Loss of entry into S phase of the cell cycle and marked induction of nuclear p53 were also observed in PDCD2 knockout blastocysts. These results demonstrate a unique role for PDCD2 in regulating the cell cycle and p53 activation during early embryonic development of the mouse.

  10. The role of salivary cortisol and DHEA-S in response to sexual, humorous, and anxiety-inducing stimuli.

    Science.gov (United States)

    Hamilton, Lisa Dawn; Meston, Cindy M

    2011-05-01

    Stress and anxiety are commonly thought to be detrimental to sexual function. Several studies in both the human and animal literature, however, have found that inducing anxiety can enhance sexual function in women. The mechanisms that explain a negative relationship between physical and psychological stress and sexual functioning are well documented, but little is known about how stress or anxiety might have a facilitatory effect on sexual arousal. As an initial step in exploring the relationship between anxiety and sexual arousal, the present study examined the role of the autonomic nervous system, and the adrenal hormones cortisol and dehydroepiandrosterone-sulfate (DHEA-S) in response to a sexual film, an anxiety-inducing film, and a humorous film. Nineteen premenopausal women (mean age 24.4 years) who were free from sexual difficulties came into the lab on three separate days. At each session they were shown an anxiety-inducing, sexually arousing, or humorous (control) film while their physiological arousal was measured. They also provided saliva samples before and after each film. Cortisol significantly decreased, while DHEA-S increased in the sexual and humorous conditions. Neither hormone changed significantly in the anxiety-inducing condition. Autonomic nervous system activity measured by heart rate and heart rate variability did not change in response to the sexual or anxiety-inducing films, but heart rate variability increased significantly in response to the humorous film. The cortisol/DHEA-S ratio at the post-sexual film time point was significantly negatively correlated with genital arousal (measured by vaginal pulse amplitude). Anxiety-inducing films did not result in a physiological stress response, which can explain why they do not impair sexual function. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Combining the auxin-inducible degradation system with CRISPR/Cas9-based genome editing for the conditional depletion of endogenous Drosophila melanogaster proteins.

    Science.gov (United States)

    Bence, Melinda; Jankovics, Ferenc; Lukácsovich, Tamás; Erdélyi, Miklós

    2017-04-01

    Inducible protein degradation techniques have considerable advantages over classical genetic approaches, which generate loss-of-function phenotypes at the gene or mRNA level. The plant-derived auxin-inducible degradation system (AID) is a promising technique which enables the degradation of target proteins tagged with the AID motif in nonplant cells. Here, we present a detailed characterization of this method employed during the adult oogenesis of Drosophila. Furthermore, with the help of CRISPR/Cas9-based genome editing, we improve the utility of the AID system in the conditional elimination of endogenously expressed proteins. We demonstrate that the AID system induces efficient and reversible protein depletion of maternally provided proteins both in the ovary and the early embryo. Moreover, the AID system provides a fine spatiotemporal control of protein degradation and allows for the generation of different levels of protein knockdown in a well-regulated manner. These features of the AID system enable the unraveling of the discrete phenotypes of genes with highly complex functions. We utilized this system to generate a conditional loss-of-function allele which allows for the specific degradation of the Vasa protein without affecting its alternative splice variant (solo) and the vasa intronic gene (vig). With the help of this special allele, we demonstrate that dramatic decrease of Vasa protein in the vitellarium does not influence the completion of oogenesis as well as the establishment of proper anteroposterior and dorsoventral polarity in the developing oocyte. Our study suggests that both the localization and the translation of gurken mRNA in the vitellarium is independent from Vasa. © 2017 Federation of European Biochemical Societies.

  12. A receptor tyrosine kinase ROR1 inhibitor (KAN0439834 induced significant apoptosis of pancreatic cells which was enhanced by erlotinib and ibrutinib.

    Directory of Open Access Journals (Sweden)

    Amir Hossein Daneshmanesh

    Full Text Available There is a great unmet medical need in pancreatic carcinoma (PC for novel drugs with other mechanisms of action than existing. PC cells express the onco-fetal RTK ROR1, absent on most normal post-partem cells. ROR1 is involved in proliferation, survival, EMT and metastasis of tumor cells in various malignancies. A small molecule inhibitor (KAN0439834 (530 Da targeting the TK domain of ROR1 was developed and the activity in ROR1 expressing human PC cell lines (n = 8 evaluated. The effects were compared to a murine mAb against the external part of ROR1, gemcitabine, erlotinib and ibrutinib. KAN0439834 induced significant apoptosis of the tumor cells. EC50 values for KAN0439834 varied between 250-650 nM depending on the cell line. The corresponding values for erlotinib and ibrutinib were 10-40 folds higher. KAN0439834 was much more effective in inducing tumor cell death than the ROR1 mAb although both inhibited ROR1 phosphorylation and downstream non-canonical Wnt pathway molecules. Combination of KAN0439834 with erlotinib or ibrutinib had significant additive effects on tumor cell death. A first-in-class small molecule ROR1 inhibitor (KAN0439834 showed promising in vitro activity against a number of human PC cell lines. Interesting is the additive effects of erlotinib and ibrutinib which warrants further studies as both these agents are in clinical trials for pancreatic carcinoma.

  13. The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

    Science.gov (United States)

    Valero, E; Gómez-Milanés, I; Almela, P; Ribeiro Do Couto, B; Laorden, M L; Milanés, M V; Núñez, C

    2018-06-08

    Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse

  14. Peripheral microcirculation during pregnancy and in women with pregnancy induced hypertension.

    Science.gov (United States)

    Ohlmann, P; Jung, F; Mrowietz, C; Alt, T; Alt, S; Schmidt, W

    2001-01-01

    During pregnancy the cardiovascular system undergoes several changes so as to adapt the maternal organism to the strains of pregnancy. These adaptations can assume a pathological development in persons with a previous history of cardiovascular problems. On the other hand the absence of these adaptations may lead to a pathological course of pregnancy. Pregnancy induced hypertension (PIH) may be such a pathological development due to maladaptation. The causes are for the most part unknown. For some time it has been assumed that it is due to microcirculatory disorders. Using periungual capillary microscopy the present study prospectively investigated the changes in peripheral microcirculation during pregnancy focussing on pregnancy induced hypertension. Sixty-seven women with a normal course of pregnancy and 28 women with pregnancy induced hypertension were evaluated. Throughout the prospective study 3 examinations were performed during pregnancy and one during childbed. The women who developed a PIH were registered during the third trimester. Erythrocyte velocity at rest and vascular reagibility of capillaries following a 3 minute ischaemia were evaluated. In the course of pregnancy a significant increase of approximately 30% in erythrocyte velocity could be observed. Interpolation to obtain the best strait line result demonstrates that it is a continuous increase. Erythrocyte velocity returns to normal in the course of 14 weeks post partum. Due to a physiological vasodilatation during pregnancy, vascular reaction to ischaemic stress significantly decreases. During childbed these changes return to normal. Examinations on women with pregnancy induced hypertension not only showed a significant reduction of microcirculation under resting conditions but also a different pattern of reaction to ischaemic stress. Erythrocyte velocity under resting conditions lies 36% below normal values. Furthermore the distinctly shortened hyperaemic period indicates a hightened

  15. Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

    Science.gov (United States)

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

  16. Character, distribution, and ecological significance of storm wave-induced scour in Rhode Island Sound, USA

    Science.gov (United States)

    McMullen, Katherine Y.; Poppe, Lawrence J.; Parker, Castle E.

    2015-01-01

    Multibeam bathymetry, collected during NOAA hydrographic surveys in 2008 and 2009, is coupled with USGS data from sampling and photographic stations to map the seabed morphology and composition of Rhode Island Sound along the US Atlantic coast, and to provide information on sediment transport and benthic habitats. Patchworks of scour depressions cover large areas on seaward-facing slopes and bathymetric highs in the sound. These depressions average 0.5-0.8 m deep and occur in water depths reaching as much as 42 m. They have relatively steep well-defined sides and coarser-grained floors, and vary strongly in shape, size, and configuration. Some individual scour depressions have apparently expanded to combine with adjacent depressions, forming larger eroded areas that commonly contain outliers of the original seafloor sediments. Where cobbles and scattered boulders are present on the depression floors, the muddy Holocene sands have been completely removed and the winnowed relict Pleistocene deposits exposed. Low tidal-current velocities and the lack of obstacle marks suggest that bidirectional tidal currents alone are not capable of forming these features. These depressions are formed and maintained under high-energy shelf conditions owing to repetitive cyclic loading imposed by high-amplitude, long-period, storm-driven waves that reduce the effective shear strength of the sediment, cause resuspension, and expose the suspended sediments to erosion by wind-driven and tidal currents. Because epifauna dominate on gravel floors of the depressions and infauna are prevalent in the finer-grained Holocene deposits, it is concluded that the resultant close juxtaposition of silty sand-, sand-, and gravel-dependent communities promotes regional faunal complexity. These findings expand on earlier interpretations, documenting how storm wave-induced scour produces sorted bedforms that control much of the benthic geologic and biologic diversity in Rhode Island Sound.

  17. Significance of exercise-induced ST segment depression in patients with myocardial infarction involving the left circumflex artery. Evaluation by exercise thallium-201 myocardial single photon emission computed tomography

    International Nuclear Information System (INIS)

    Koitabashi, Norimichi; Toyama, Takuji; Hoshizaki, Hiroshi

    2000-01-01

    The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography (Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement (angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V 2 , V 3 and V 4 leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aV F , V 5 and V 6 leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression (p<0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium. (author)

  18. High-Density Plasma-Induced Etch Damage of GaN

    International Nuclear Information System (INIS)

    Baca, A.G.; Han, J.; Lester, L.F.; Pearton, S.J.; Ren, F.; Shul, R.J.; Willison, C.G.; Zhang, L.; Zolper, J.C.

    1999-01-01

    Anisotropic, smooth etching of the group-III nitrides has been reported at relatively high rates in high-density plasma etch systems. However, such etch results are often obtained under high de-bias and/or high plasma flux conditions where plasma induced damage can be significant. Despite the fact that the group-III nitrides have higher bonding energies than more conventional III-V compounds, plasma-induced etch damage is still a concern. Attempts to minimize such damage by reducing the ion energy or increasing the chemical activity in the plasma often result in a loss of etch rate or anisotropy which significantly limits critical dimensions and reduces the utility of the process for device applications requiring vertical etch profiles. It is therefore necessary to develop plasma etch processes which couple anisotropy for critical dimension and sidewall profile control and high etch rates with low-damage for optimum device performance. In this study we report changes in sheet resistance and contact resistance for n- and p-type GaN samples exposed to an Ar inductively coupled plasma (ICP). In general, plasma-induced damage was more sensitive to ion bombardment energies as compared to plasma flux. In addition, p-GaN was typically more sensitive to plasma-induced damage as compared to n-GaN

  19. Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions.

    Science.gov (United States)

    Han, Ting-Li; Tumanov, Sergey; Cannon, Richard D; Villas-Boas, Silas G

    2013-01-01

    Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis.

  20. Mechanisms of Radiation-Induced Conditioned Taste Aversion Learning

    Science.gov (United States)

    1986-01-01

    impairment of the synthesis of these cells, especially those in In addition to emesis. exposure to lower doses of ionizing bone marrow. However. since...pretreatment with fluoxetine in gustatory conditioning. 629-635. 1983. Pharmnat l Bioc/n-a 8,4,ui 17: 431-443. 1982. 100. Rabin. B. M. and J. S. Rabin

  1. Preference conditioning in healthy individuals: correlates with hazardous drinking.

    Science.gov (United States)

    Balodis, Iris M; Lockwood, Kathleen P; Magrys, Sylvia A; Olmstead, Mary C

    2010-06-01

    Conditioned reward is a classic measure of drug-induced brain changes in animal models of addiction. The process can be examined in humans using the Conditioned Pattern Preference (CPP) task, in which participants associate nonverbal cues with reward but demonstrate low awareness of this conditioning. Previously, we reported that alcohol intoxication does not affect CPP acquisition in humans, but our data indicated that prior drug use may impact conditioning scores. To test this possibility, the current study examined the relationship between self-reported alcohol use and preference conditioning in the CPP task. Working memory was assessed during conditioning by asking participants to count the cues that appeared at each location on a computer screen. Participants (69 female and 23 male undergraduate students) completed the Alcohol Use Disorders Identification Test (AUDIT) and the Rutgers Alcohol Problem Index (RAPI) as measures of hazardous drinking. Self-reported hazardous drinking was significantly correlated with preference conditioning in that individuals who scored higher on these scales exhibited an increased preference for the reward-paired cues. In contrast, hazardous drinking did not affect working memory errors on the CPP task. These findings support evidence that repeated drug use sensitizes neural pathways mediating conditioned reward and point to a neurocognitive disposition linking substance misuse and responses to reward-paired stimuli. The relationship between hazardous drinking and conditioned reward is independent of changes in cognitive function, such as working memory.

  2. Drought-Induced Leaf Proteome Changes in Switchgrass Seedlings

    Directory of Open Access Journals (Sweden)

    Zhujia Ye

    2016-08-01

    Full Text Available Switchgrass (Panicum virgatum is a perennial crop producing deep roots and thus highly tolerant to soil water deficit conditions. However, seedling establishment in the field is very susceptible to prolonged and periodic drought stress. In this study, a “sandwich” system simulating a gradual water deletion process was developed. Switchgrass seedlings were subjected to a 20-day gradual drought treatment process when soil water tension was increased to 0.05 MPa (moderate drought stress and leaf physiological properties had expressed significant alteration. Drought-induced changes in leaf proteomes were identified using the isobaric tags for relative and absolute quantitation (iTRAQ labeling method followed by nano-scale liquid chromatography mass spectrometry (nano-LC-MS/MS analysis. Additionally, total leaf proteins were processed using a combinatorial library of peptide ligands to enrich for lower abundance proteins. Both total proteins and those enriched samples were analyzed to increase the coverage of the quantitative proteomics analysis. A total of 7006 leaf proteins were identified, and 257 (4% of the leaf proteome expressed a significant difference (p < 0.05, fold change <0.6 or >1.7 from the non-treated control to drought-treated conditions. These proteins are involved in the regulation of transcription and translation, cell division, cell wall modification, phyto-hormone metabolism and signaling transduction pathways, and metabolic pathways of carbohydrates, amino acids, and fatty acids. A scheme of abscisic acid (ABA-biosynthesis and ABA responsive signal transduction pathway was reconstructed using these drought-induced significant proteins, showing systemic regulation at protein level to deploy the respective mechanism. Results from this study, in addition to revealing molecular responses to drought stress, provide a large number of proteins (candidate genes that can be employed to improve switchgrass seedling growth and

  3. An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis Conditions, with or without Active Dry Yeast Supplementation

    Directory of Open Access Journals (Sweden)

    Suzanne L. Ishaq

    2017-10-01

    Full Text Available Sub-acute ruminal acidosis (SARA is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs but not diversity (Inverse Simpson, Shannon, but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly (P < 0.05 affected the abundance of numerous fungal genera as seen in the high-fiber diet: Lewia, Neocallimastix, and Phoma were increased, while Alternaria, Candida Orpinomyces, and Piromyces spp. were decreased. Likewise, for protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium furca spp. Multivariate analyses showed diet type was most significant in driving diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac. Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor (P = 0.001, Monte Carlo correction for protozoa

  4. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women.

    Science.gov (United States)

    Heinrich, Ulrike; Neukam, Karin; Tronnier, Hagen; Sies, Helmut; Stahl, Wilhelm

    2006-06-01

    Dietary antioxidants contribute to endogenous photoprotection and are important for the maintenance of skin health. In the present study, 2 groups of women consumed either a high flavanol (326 mg/d) or low flavanol (27 mg/d) cocoa powder dissolved in 100 mL water for 12 wk. Epicatechin (61 mg/d) and catechin (20 mg/d) were the major flavanol monomers in the high flavanol drink, whereas the low flavanol drink contained 6.6 mg epicatechin and 1.6 mg catechin as the daily dose. Photoprotection and indicators of skin condition were assayed before and during the intervention. Following exposure of selected skin areas to 1.25 x minimal erythemal dose (MED) of radiation from a solar simulator, UV-induced erythema was significantly decreased in the high flavanol group, by 15 and 25%, after 6 and 12 wk of treatment, respectively, whereas no change occurred in the low flavanol group. The ingestion of high flavanol cocoa led to increases in blood flow of cutaneous and subcutaneous tissues, and to increases in skin density and skin hydration. Skin thickness was elevated from 1.11 +/- 0.11 mm at wk 0 to 1.24 +/- 0.13 mm at wk 12; transepidermal water loss was diminished from 8.7 +/- 3.7 to 6.3 +/- 2.2 g/(h x m2) within the same time frame. Neither of these variables was affected in the low flavanol cocoa group. Evaluation of the skin surface showed a significant decrease of skin roughness and scaling in the high flavanol cocoa group compared with those at wk 12. Dietary flavanols from cocoa contribute to endogenous photoprotection, improve dermal blood circulation, and affect cosmetically relevant skin surface and hydration variables.

  5. Memory accessibility and medical decision-making for significant others: The role of socially-shared retrieval induced forgetting

    Directory of Open Access Journals (Sweden)

    Dora M Coman

    2013-06-01

    Full Text Available Medical decisions will often entail a broad search for relevant information. No sources alone may offer a complete picture, and many may be selective in their presentation. This selectivity may induce forgetting for previously learned material, thereby adversely affecting medical decision-making. In the study phase of two experiments, participants learned information about a fictitious disease and advantages and disadvantages of four treatment options. In the subsequent practice phase, they read a pamphlet selectively presenting either relevant (Experiment 1 or irrelevant (Experiment 2 advantages or disadvantages. A final cued recall followed and, in Experiment 2, a decision as to the best treatment for a patient. Not only did reading the pamphlet induce forgetting for related and unmentioned information, the induced forgetting adversely affected decision-making. The research provides a cautionary note about the risks of searching through selectively presented information when making a medical decision.

  6. Inhibitory Effect of Endostar on Specific Angiogenesis Induced by Human Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Qing Ye

    2015-01-01

    Full Text Available To investigate the effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma, this research systematically elucidated the inhibitory effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We employed fluorescence quantitative Boyden chamber analysis, wound-healing assay, flow cytometry examination using a coculture system, quantitative analysis of tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media (HCM and HepG2 compared with normal hepatocyte conditioned media (NCM and L02. Then, we found that endostar as a tumor angiogenesis inhibitor could potently inhibit human umbilical vein endothelial cell (HUVEC migration in response to HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24 hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In vivo Matrigel plug formation was also significantly reduced by endostar in HepG2 inducing system rather than in L02 inducing system. It could be concluded that, at cell level, endostar inhibited the angiogenesis-related biological behaviors of HUVEC in response to HCC, including migration, adhesion proliferation, and tube formation. At animal level, endostar inhibited the angiogenesis in response to HCC in Matrigel matrix.

  7. Protein S-glutathionylation induced by hypoxia increases hypoxia-inducible factor-1α in human colon cancer cells.

    Science.gov (United States)

    Jeon, Daun; Park, Heon Joo; Kim, Hong Seok

    2018-01-01

    Hypoxia is a common characteristic of many types of solid tumors. Intratumoral hypoxia selects for tumor cells that survive in a low oxygen environment, undergo epithelial-mesenchymal transition, are more motile and invasive, and show gene expression changes driven by hypoxia-inducible factor-1α (HIF-1α) activation. Therefore, targeting HIF-1α is an attractive strategy for disrupting multiple pathways crucial for tumor growth. In the present study, we demonstrated that hypoxia increases the S-glutathionylation of HIF-1α and its protein levels in colon cancer cells. This effect is significantly prevented by decreasing oxidized glutathione as well as glutathione depletion, indicating that S-glutathionylation and the formation of protein-glutathione mixed disulfides is related to HIF-1α protein levels. Moreover, colon cancer cells expressing glutaredoxin 1 are resistant to inducing HIF-1α and expressing hypoxia-responsive genes under hypoxic conditions. Therefore, S-glutathionylation of HIF-1α induced by tumor hypoxia may be a novel therapeutic target for the development of new drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Clinicopathologic significance of fascin, extracellular matrix metalloproteinase inducer, and ezrin expressions in colorectal adenocarcinoma

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    Eun-Joo Jung

    2011-01-01

    Full Text Available Background: The over expression of fascin, extracellular matrix metalloproteinase inducer (EMMPRIN, and ezrin proteins has been associated with poor prognosis in various carcinomas and sarcomas. However, very few studies have reported the relationship between the expression of fascin, EMMPRIN, and ezrin proteins and the clinico-pathologic parameters of colorectal carcinomas. Aims: The aim was to investigate the relationship between fascin, EMMPRIN, and ezrin proteins in colorectal adenocarcinomas and their correlation with clinico-pathologic parameters. Settings and Design: The expression of fascin, EMMPRIN, and ezrin proteins was studied in 210 colorectal adenocarcinoma patients through immunohistochemical staining. Materials and Methods: Immunohistochemical staining by the avidin-biotin peroxidase method was done. The scoring of each protein expression was done and divided into three groups (negative, low-, and high-expression groups. Statistical Analysis: A chi-square test, and Kendall′s tau-b correlation test were used for comparing. Survival analysis was performed using the Kaplan-Meier method with log-rank tests and the Cox proportional hazard model. Results: The percentages of the high-expression group of fascin, EMMPRIN, and ezrin proteins in colorectal adenocarcinomas were 24%, 73%, and 62%, respectively. Weak positive correlations were observed among these protein expressions. An increased expression of the fascin protein was significantly associated with advanced tumor depth and shorter survival times, and a high expression of fascin protein was an independent prognostic factor in univariate and multivariate survival analyses. EMMPRIN and ezrin protein expressions were not associated with the clinico-pathologic parameters. Conclusions: The high expression of fascin protein may be an unfavorable prognostic marker for individual colorectal cancer patients.

  9. Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

    Science.gov (United States)

    Shang, Xueliang; Shang, Yingchun; Fu, Jingxuan; Zhang, Tao

    2017-08-01

    The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

  10. An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis Conditions, with or without Active Dry Yeast Supplementation.

    Science.gov (United States)

    Ishaq, Suzanne L; AlZahal, Ousama; Walker, Nicola; McBride, Brian

    2017-01-01

    Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae ) supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly ( P PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor ( P = 0.001, Monte Carlo correction) for protozoa. Diet-induced SARA shifts diversity of rumen fungi and protozoa and selects against fiber-degrading species. Supplementation with ADY mitigated this reduction in protozoa, presumptively by triggering microbial diversity shifts (as seen even in the high-fiber diet) that resulted in pH stabilization. ADY did not recover the initial community structure that was seen in pre-SARA conditions.

  11. Role of crucible partition in improving Czochralski melt conditions

    Science.gov (United States)

    Jafri, I. H.; Prasad, V.; Anselmo, A. P.; Gupta, K. P.

    1995-09-01

    Many of the inhomogeneities and defects in the crystal grown from a pool of melt are because of the inherent unsteady growth kinetics and flow instabilities of the process. A scaled up version of the Czochralski process induces oscillatory and turbulent conditions in the melt, thereby resulting in the production of non-uniform silicon crystals. This numerical study reveals that a crucible partition shorter than the melt height can significantly improve the melt conditions. The obstruction at the bottom of the crucible is helpful but the variations in heat flux and flow patterns remain random. However, when the obstruction is introduced at the top of the melt, the flow conditions become much more desirable and oscillations are greatly suppressed. It is also found that a full-melt height partition or a double-crucible may not be a good choice. An optimal size of the blockage and its location to produce the most desirable process conditions will depend on the growth parameters including the melt height and the crucible diameter. These findings should be particularly useful in designing a solid polysilicon pellets-feed continuous Czochralski process for Si crystals.

  12. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  13. Nutritional Interventions for Cancer-induced Cachexia

    Science.gov (United States)

    Gullett, Norleena P.; Mazurak, Vera; Hebbar, Gautam; Ziegler, Thomas R.

    2011-01-01

    Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathologic mechanisms causing cachexia resulting in well-meaning advice to increase caloric intake with minimal results. Our goal is to describe the pathologic basis of cancer-induced cachexia and to detail accompanying metabolic derangements. Understanding the causes of cachexia sheds light on the subsequent need for multi-modality therapy including clinical intervention with specialized nutrition support, drug therapy, lifestyle and diet changes. In addition to nutrition support modalities, practicing oncologists may prescribe medical therapies designed to increase body weight and lean body mass, including megestrol acetate, tetrahydrocannibinol, oxandrolone, and non-steroidal anti-inflammatory drugs. A variety of experimental therapies are also being investigated for cancer-induced cachexia including tumor necrosis factor-alpha inhibitors and ghrelin infusions. We review the available data to support nutrition-oriented interventions in cancer-induced cachexia, including omega-3 fatty acids, amino-acid loading/protein supplementation, parenteral and enteral nutrition support, and food-derived compounds such as curcumin, reservatrol, and pomegranate. PMID:21420558

  14. Quantifying the Clinical Significance of Cannabis Withdrawal

    Science.gov (United States)

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  15. Quantifying the clinical significance of cannabis withdrawal.

    Directory of Open Access Journals (Sweden)

    David J Allsop

    Full Text Available Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001.Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

  16. Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

    Science.gov (United States)

    Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

    2016-02-01

    The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (Ppannus of an AIA model. Thus, this could become a safe and effective non-viral gene transfection procedure for arthritis therapy. Copyright © 2015 Elsevier B.V. All rights

  17. Neutron induced bystander effect among zebrafish embryos

    Science.gov (United States)

    Ng, C. Y. P.; Kong, E. Y.; Kobayashi, A.; Suya, N.; Uchihori, Y.; Cheng, S. H.; Konishi, T.; Yu, K. N.

    2015-12-01

    The present paper reported the first-ever observation of neutron induced bystander effect (NIBE) using zebrafish (Danio rerio) embryos as the in vivo model. The neutron exposure in the present work was provided by the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. Two different strategies were employed to induce NIBE, namely, through directly partnering and through medium transfer. Both results agreed with a neutron-dose window (20-50 mGy) which could induce NIBE. The lower dose limit corresponded to the threshold amount of neutron-induced damages to trigger significant bystander signals, while the upper limit corresponded to the onset of gamma-ray hormesis which could mitigate the neutron-induced damages and thereby suppress the bystander signals. Failures to observe NIBE in previous studies were due to using neutron doses outside the dose-window. Strategies to enhance the chance of observing NIBE included (1) use of a mono-energetic high-energy (e.g., between 100 keV and 2 MeV) neutron source, and (2) use of a neutron source with a small gamma-ray contamination. It appeared that the NASBEE facility used in the present study fulfilled both conditions, and was thus ideal for triggering NIBE.

  18. Maturation of human dendritic cells by monocyte-conditioned medium is dependent upon trace amounts of lipopolysaccharide inducing tumour necrosis factor alpha

    DEFF Research Database (Denmark)

    Nersting, Jacob; Svenson, Morten; Andersen, Vagn

    2003-01-01

    We investigated the ability of monocyte-conditioned medium (MCM), generated by monocytes cultured on plastic-immobilised immunoglobulin, to stimulate maturation of human monocyte-derived dendritic cells (DC). Earlier reports suggest that MCM is a strong inducer of irreversible DC maturation......, whereas we find, that adding a small amount of lipopolysaccharide (LPS) to the MCM-generating cultures is required for the production of a DC-stimulatory MCM. Moreover, compared with addition of LPS directly to the DC cultures, stimulation via MCM cultures increases by several fold the DC...

  19. Extending Injury- and Disease-Resistant CNS Phenotypes by Repetitive Epigenetic Conditioning

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Gidday

    2015-03-01

    Full Text Available Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist – in effect, expanding conditioning’s therapeutic window – would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1-3 days protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances postischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neuroplasticity remain largely unstudied, accumulating empirical evidence supports the contention that all of these adaptive phenotypes are epigenetically mediated. Going forward, additional preclinical demonstrations of the ability to induce sustained beneficial phenotypes that reduce the burden of acute and chronic neurodegeneration, and experimental interrogations of the regulatory constructs responsible for these epigenetic responses, will accelerate the identification of not only efficacious, but practical, adaptive epigenetics-based treatments for individuals with neurological disease.

  20. Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking

    Science.gov (United States)

    Chaudhri, N.; Woods, C. A.; Sahuque, L.L.; Gill, T. M.; Janak, P.H.

    2014-01-01

    Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself, as well as serial connectivity between the basolateral amygdala (BLA) and nucleus accumbens core (NAC core), were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male, Long-Evans rats were trained to discriminate between two conditioned stimuli (CS) - a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 ml/CS+, 3.2 ml/session) and a CS− that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS− without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of gamma-amino-butyric-acid receptor agonists (0.1 mM muscimol and 1.0 mM baclofen; M/B; 0.3 µl/side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 µg/side), or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context. PMID:23758059

  1. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    International Nuclear Information System (INIS)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging

  2. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

  3. The Responses of Antioxidant System against the Heavy Metal-Induced Stress in Tomato

    Directory of Open Access Journals (Sweden)

    Dursun KISA

    2017-12-01

    Full Text Available Plants maintain their life cycles under the various environmental conditions such as oxidative stress induced by heavy metals. Accumulation of metal ions in plants causes the formation of free radicals and stimulates the antioxidative defense systems. In this study, the activities of APX, POD, and SOD are investigated in the leaves and roots of tomato cultivated under the heavy metal-induced stress. The activities of APX, POD, and SOD exhibited remarkable induction with the treatment of Cd, Cu and Pb (10, 20 and 50 ppm in the leaves of tomato compared to control plants except for 50 ppm Pb. In roots, APX activity changed depending on the heavy metal types and concentrations, while Cd clearly increased it with stress conditions, but Cu decreased in tomato compared to control. The activity of POD clearly exhibited that the all doses of heavy metals reduced the enzyme activity in roots polluted with heavy metals. The treatment of Cd (10, 20 and 50 ppm significantly increased the activity of SOD, however, Cu showed the opposite effect which significantly decreased with increasing doses in roots compared to uncontaminated plants. Also, roots from plants grown on the high concentration of Pb (20 and 50 ppm induced the activity of SOD. Briefly, it is clear responses which Cd significantly raised the activities of APX and SOD in leaves and roots of tomato. The decreases caused by these metals in the activity of POD and Cu in the activities of APX and SOD in roots of tomato can be clarified by the result of heavy metal-induced the over production of free radical.

  4. Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions.

    Directory of Open Access Journals (Sweden)

    Zhuo-Xin Cheng

    Full Text Available Epithelial to mesenchymal transition (EMT induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear.Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype.These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.

  5. The significance of thermohydraulic conditions for the corrosion safety of PWR steam generators

    International Nuclear Information System (INIS)

    Gulich, J.F.

    1975-04-01

    In several PWR nuclear power plants leakages have occurred in the steam generator which were caused by localised corrosion attack. While the attention of manufacturers and operators is focused on the influences of feedwater chemistry and tube material, the present work highlights the fact that the damage always occurred in those places where flow regimed are poorly defined. The investigation leads to the result that local dry out of the heating surface can be contributing cause of damage. A method is indicated for estimating the thermohydraulic conditions in the inflow region over the tube plate and measures to improve corrosion safety are discussed. (author)

  6. Modulation of Radiation responses by pre-exposure to irradiated Cell conditioned medium.

    LENUS (Irish Health Repository)

    Maguire, Paula

    2007-04-01

    The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCM-induced adaptive response in HPV-G cells "primed" with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM.

  7. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    International Nuclear Information System (INIS)

    Kyotani, Yoji; Ota, Hiroyo; Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo; Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu; Takasawa, Shin; Kimura, Hiroshi; Uno, Masayuki; Yoshizumi, Masanori

    2013-01-01

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

  8. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

    2013-11-15

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

  9. Task-induced frequency modulation features for brain-computer interfacing.

    Science.gov (United States)

    Jayaram, Vinay; Hohmann, Matthias; Just, Jennifer; Schölkopf, Bernhard; Grosse-Wentrup, Moritz

    2017-10-01

    Task-induced amplitude modulation of neural oscillations is routinely used in brain-computer interfaces (BCIs) for decoding subjects' intents, and underlies some of the most robust and common methods in the field, such as common spatial patterns and Riemannian geometry. While there has been some interest in phase-related features for classification, both techniques usually presuppose that the frequencies of neural oscillations remain stable across various tasks. We investigate here whether features based on task-induced modulation of the frequency of neural oscillations enable decoding of subjects' intents with an accuracy comparable to task-induced amplitude modulation. We compare cross-validated classification accuracies using the amplitude and frequency modulated features, as well as a joint feature space, across subjects in various paradigms and pre-processing conditions. We show results with a motor imagery task, a cognitive task, and also preliminary results in patients with amyotrophic lateral sclerosis (ALS), as well as using common spatial patterns and Laplacian filtering. The frequency features alone do not significantly out-perform traditional amplitude modulation features, and in some cases perform significantly worse. However, across both tasks and pre-processing in healthy subjects the joint space significantly out-performs either the frequency or amplitude features alone. This result only does not hold for ALS patients, for whom the dataset is of insufficient size to draw any statistically significant conclusions. Task-induced frequency modulation is robust and straight forward to compute, and increases performance when added to standard amplitude modulation features across paradigms. This allows more information to be extracted from the EEG signal cheaply and can be used throughout the field of BCIs.

  10. Calcium in the Mechanism of Ammonia-Induced Astrocyte Swelling

    Science.gov (United States)

    Jayakumar, A.R.; Rao, K.V. Rama; Tong, X.Y; Norenberg, M.D.

    2016-01-01

    Brain edema, due largely to astrocyte swelling, is an important clinical problem in patients with acute liver failure. While mechanisms underlying astrocyte swelling in this condition are not fully understood, ammonia and associated oxidative/nitrosative stress (ONS) appear to be involved. Mechanisms responsible for the increase in reactive oxygen/nitrogen species (RONS) and their role in ammonia-induced astrocyte swelling, however, are poorly understood. Recent studies have demonstrated a transient increase in intracellular Ca2+ in cultured astrocytes exposed to ammonia. As Ca2+ is a known inducer of RONS, we investigated potential mechanisms by which Ca2+ may be responsible for the production of RONS and cell swelling in cultured astrocytes after treatment with ammonia. Exposure of cultured astrocytes to ammonia (5 mM) increased the formation of free radicals, including nitric oxide, and such increase was significantly diminished by treatment with the Ca2+ chelator BAPTA-AM. We then examined the activity of Ca2+-dependent enzymes that are known to generate RONS and found that ammonia significantly increased the activities of NADPH oxidase (NOX), constitutive nitric oxide synthase (cNOS) and phospholipase A2 (PLA2) and such increases in activity were significantly diminished by BAPTA. Pretreatment of cultures with 7-nitroindazole, apocyanin and quinacrine, respective inhibitors of cNOS, NOX and PLA2, all significantly diminished RONS production. Additionally, treatment of cultures with BAPTA or with inhibitors of cNOS, NOX and PLA2 reduced ammonia-induced astrocyte swelling. These studies suggest that the ammonia-induced rise in intracellular Ca2+ activates free radical producing enzymes that ultimately contribute to the mechanism of astrocyte swelling. PMID:19393035

  11. Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Masako, E-mail: n-masako@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Morita, Yoshihiro [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Department of Oral and Maxillofacial Surgery, Seichokai Hannan Municipal Hospital, Hannan, Osaka 599-0202 (Japan); Hata, Kenji [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Muragaki, Yasuteru, E-mail: ymuragak@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan)

    2016-07-15

    Local acidosis is one of the characteristic features of the cancer microenvironment. Many reports indicate that acidosis accelerates the proliferation and invasiveness of cancer cells. However, whether acidic conditions affect lymphatic metastasis is currently unknown. In the present study, we focused on the effects of acidosis on lymphatic endothelial cells (LECs) to assess the relationship between acidic microenvironments and lymph node metastasis. We demonstrated that normal human LECs express various acid receptors by immunohistochemistry and reverse transcriptase-polymerase chain reaction (PCR). Acidic stimulation with low pH medium induced morphological changes in LECs to a spindle shape, and significantly promoted cellular growth and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of interleukin (IL)-8. Acidic stimulation increased IL-8 production in LECs, whereas a selective transient receptor potential vanilloid subtype 1 (TRPV1) antagonist, 5′-iodoresiniferatoxin, decreased IL-8 production. IL-8 accelerated the proliferation of LECs, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of nuclear factor (NF)-κB was induced by acidic conditions, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironments in tumors induce lymphangiogenesis via TRPV1 activation in LECs, which in turn may promote lymphatic metastasis. - Highlights: • Acidity accelerates the growth, migration, and tube formation of LECs. • Acidic condition induces IL-8 expression in LECs. • IL-8 is critical for the changes of LECs. • IL-8 expression is induced via TRPV1 activation.

  12. Chromosomal radiosensitivity: a study of the chromosomal G2 assay in human blood lymphocytes indicating significant inter-individual variability

    International Nuclear Information System (INIS)

    Smart, V.; Curwen, G.B.; Whitehouse, C.A.; Edwards, A.; Tawn, E.J.

    2003-01-01

    The G 2 chromosomal radiosensitivity assay is a technically demanding assay. To ensure that it is reproducible in our laboratory, we have examined the effects of storage and culture conditions by applying the assay to a group of healthy controls and determined the extent of intra- and inter-individual variations. Nineteen different individuals provided one or more blood samples resulting in a total of 57 successful tests. Multiple cultures from a single blood sample showed no statistically significant difference in the number of chromatid type aberrations between cultures. A 24 h delay prior to culturing the lymphocytes did not significantly affect the induced G 2 score. Intra-individual variation was not statistically significant in seven out of nine individuals. Inter-individual variation was highly statistically significant (P<0.001), indicating that there is a real difference between individuals in the response to radiation using this assay

  13. Functional significance of metastasis-inducing S100A4(Mts1) in tumor-stroma interplay

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Birgitte; Klingelhöfer, Jörg; Grum-Schwensen, Birgitte

    2004-01-01

    Causal implication of S100A4 in inducing metastases was convincingly shown previously. However, the mechanisms that associate S100A4 with tumor progression are not well understood. S100A4 protein, as a typical member of the S100 family, exhibits dual, intracellular and extracellular, functions. T...

  14. Clinical significance of determination of changes of plasma Hcy and serum folic acid and vitamin B{sub 12} levels in patients with pregnancy induced hypertension complicated with nephr opathy

    Energy Technology Data Exchange (ETDEWEB)

    Dongxia, Zhou; Xiaoli, Pan; Fangwen, Xie; Jifeng, Fan [Shuyang County People' s Hospital, Jiangsu, Shuyang (China)

    2007-10-15

    Objective: To investigate the clinical significance of changes of plasma homocysteine (Hcy), serum folic acid and vitamin B{sub 12} levels in patients with pregnancy induced hypertension (PIH) complicated with nephropathy. Methods: Plasma Hcy levels was measured with immuno chemistry and serum folic acid and vitamin B{sub 12} levels were detected with RIA in 32 pregnant women with PIH complicated with nephrophy and 70 pregnant women with PIH but without nephrophy and 35 pregnant women without PIH (as controls). Results; The plasma Hcy levels in patients with PIH were significantly higher than those without (i.e. controls) (P<0.01), while the serum folic acid, vitaminB{sub 12} levels decreased markedly (P<0.01). Among the pregnant women with PIH, plasma Hcy levels were significantly higher and serum folic acid, B{sub 12} levels were significantly lower in the patients complicated with nepropathy than those in patients without nephropathy (P<0.01). conclusion: Determination of plasma Hcy and serum folic acid and vitaminB{sub 12} levels is clinically useful in the management in patients with pregnancy induced hypertension complicated with nephropthy. (authors)

  15. Recombinant adeno-associated virus-delivered hypoxia-inducible stanniocalcin-1 expression effectively inhibits hypoxia-induced cell apoptosis in cardiomyocytes.

    Science.gov (United States)

    Shi, Xin; Wang, Jianzhong; Qin, Yan

    2014-12-01

    Ischemia/hypoxia-induced oxidative stress is detrimental for the survival of cardiomyocytes and cardiac function. Stanniocalcin-1 (STC-1), a glycoprotein, has been found to play an inhibitory role in the production of reactive oxygen species (ROS). Here, we speculated that the overexpression of STC-1 might alleviate oxidative damage in cardiomyocytes under conditions of hypoxia. To control the expression of STC-1 in hypoxia, we constructed a recombinant adeno-associated virus (AAV) carrying the hypoxia-responsive element (HRE) to mediate hypoxia induction. Cardiomyocytes were infected with AAV-HRE-STC-1 and cultured in normoxic or hypoxic conditions, and STC-1 overexpression was only detected in hypoxic cultured cardiomyocytes by using quantitative real-time polymerase chain reaction and Western blot analysis. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, AAV-HRE-STC-1 infection was shown to significantly enhance cell survival under hypoxia. Hypoxia-induced cell apoptosis was inhibited by AAV-HRE-STC-1 infection by using the Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide apoptosis assay. Moreover, the proapoptotic protein Caspase-3 and anti-apoptotic protein Bcl-2, which were dysregulated by hypoxia, were reversed by AAV-HRE-STC-1 infection. AAV-HRE-STC-1-mediated STC-1 overexpression markedly inhibited ROS production in cardiomyocytes cultured under hypoxic conditions. AAV-HRE-STC-1 infection significantly upregulated uncoupled protein 3 (UCP3), whereas silencing of UCP3 blocked the inhibitory effect of AAV-HRE-STC-1 on ROS production. In contrast, AAV-HRE-STC-1 infection had no effect on UCP2, and knockdown of UCP2 did not block the inhibitory effect of AAV-HRE-STC-1 on ROS production in the cardiomyocytes cultured under hypoxic conditions. Taken together, STC1 activates antioxidant pathway in cardiomyocytes through the induction of UCP3, implying that AAV-HRE-STC-1 has potential in the treatment of ischemic

  16. Physical renormalization condition for de Sitter QED

    Science.gov (United States)

    Hayashinaka, Takahiro; Xue, She-Sheng

    2018-05-01

    We considered a new renormalization condition for the vacuum expectation values of the scalar and spinor currents induced by a homogeneous and constant electric field background in de Sitter spacetime. Following a semiclassical argument, the condition named maximal subtraction imposes the exponential suppression on the massive charged particle limit of the renormalized currents. The maximal subtraction changes the behaviors of the induced currents previously obtained by the conventional minimal subtraction scheme. The maximal subtraction is favored for a couple of physically decent predictions including the identical asymptotic behavior of the scalar and spinor currents, the removal of the IR hyperconductivity from the scalar current, and the finite current for the massless fermion.

  17. A comparison of hydrogen vs. helium glow discharge effects on fusion device first-wall conditioning

    International Nuclear Information System (INIS)

    Dylla, H.F.

    1989-09-01

    Hydrogen- and deuterium-fueled glow discharges are used for the initial conditioning of magnetic fusion device vacuum vessels following evacuation from atmospheric pressure. Hydrogenic glow discharge conditioning (GDC) significantly reduces the near-surface concentration of simple adsorbates, such as H 2 O, CO, and CH 4 , and lowers ion-induced desorption coefficients by typically three orders of magnitude. The time evolution of the residual gas production observed during hydrogen-glow discharge conditioning of the carbon first-wall structure of the TFTR device is similar to the time evolution observed during hydrogen GDC of the initial first-wall configuration in TFTR, which was primarily stainless steel. Recently, helium GDC has been investigated for several wall-conditioning tasks on a number of tokamaks including TFTR. Helium GDC shows negligible impurity removal with stainless steel walls. For impurity conditioning with carbon walls, helium GDC shows significant desorption of H 2 O, CO, and CO 2 ; however, the total desorption yield is limited to the monolayer range. In addition, helium GDC can be used to displace hydrogen isotopes from the near-surface region of carbon first-walls in order to lower hydrogenic retention and recycling. 38 refs., 6 figs

  18. Radiation-induced inhibition of human lymphocyte blastogenesis: the effect of superoxide dismutase and catalase

    International Nuclear Information System (INIS)

    Knox, S.; Misra, H.P.; Shifrine, M.

    1982-01-01

    Mitogen-induced lymphocyte blastogenesis was measured following X-irradiation (0-4 Gy) in the presence or absence of superoxide dismutase (SOD), under aerobic and anaerobic conditions. There were no significant differences between radiation survival curves under these different conditions, nor did SOD have any radioprotective effect. This demonstrates lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following X-irradiation at 2 Gy, neither SOD nor catalase, alone or together, added before or after irradiation, were radioprotective. In comparison to controls, both enzymes depressed lymphocyte proliferation when added at levels as low as 25 μg catalase or 100 μg SOD/ml media. When SOD and catalase were added together, the greatest depression of blastogenesis was obtained with increasing levels of SOD relative to increasing levels of catalase, indicating that SOD was largely responsible for this depression. The suppressive effect of administration of SOD (p 2 - and/or H 2 O 2 are not involved in radiation-induced inhibition of lymphocyte blastogenesis. (author)

  19. γ-radiation induced corrosion of copper in bentonite-water systems under anaerobic conditions

    Science.gov (United States)

    Karin Norrfors, K.; Björkbacka, Åsa; Kessler, Amanda; Wold, Susanna; Jonsson, Mats

    2018-03-01

    In this work we have experimentally studied the impact of bentonite clay on the process of radiation-induced copper corrosion in anoxic water. The motivation for this is to further develop our understanding of radiation-driven processes occurring in deep geological repositories for spent nuclear fuel where copper canisters containing the spent nuclear fuel will be embedded in compacted bentonite. Experiments on radiation-induced corrosion in the presence and absence of bentonite were performed along with experiments elucidating the impact irradiation on the Cu2+ adsorption capacity of bentonite. The experiments presented in this work show that the presence of bentonite clay has no or very little effect on the magnitude of radiation-induced corrosion of copper in anoxic aqueous systems. The absence of a protective effect similar to that observed for radiation-induced dissolution of UO2 is attributed to differences in the corrosion mechanism. This provides further support for the previously proposed mechanism where the hydroxyl radical is the key radiolytic oxidant responsible for the corrosion of copper. The radiation effect on the bentonite sorption capacity of Cu2+ (reduced capacity) is in line with what has previously been reported for other cations. The reduced cation sorption capacity is partly attributed to a loss of Al-OH sites upon irradiation.

  20. Racemization of Valine by Impact-Induced Heating

    Science.gov (United States)

    Furukawa, Yoshihiro; Takase, Atsushi; Sekine, Toshimori; Kakegawa, Takeshi; Kobayashi, Takamichi

    2018-03-01

    Homochirality plays an important role in all living organisms but its origin remains unclear. It also remains unclear whether such chiral molecules survived terrestrial heavy impact events. Impacts of extraterrestrial objects on early oceans were frequent and could have affected the chirality of oceanic amino acids when such amino acids accumulated during impacts. This study investigated the effects of shock-induced heating on enantiomeric change of valine with minerals such as olivine ([Mg0.9, Fe0.1]2SiO4), hematite (Fe2O3), and calcite (CaCO3). With a shock wave generated by an impact at 0.8 km/s, both d- and l-enriched valine were significantly decomposed and partially racemized under all experimental conditions. Different minerals had different shock impedances; therefore, they provided different P-T conditions for identical impacts. Furthermore, the high pH of calcite promoted the racemization of valine. The results indicate that in natural hypervelocity impacts, amino acids in shocked oceanic water would have decomposed completely, since impact velocity and the duration of shock compression and heating are typically greater in hypervelocity impact events than those in experiments. Even with the shock wave by the impact of small and decelerated projectiles in which amino acids survive, the shock heating may generate sufficient heat for significant racemization in shocked oceanic water. However, the duration of shock induced heating by small projectiles is limited and the population of such decelerated projectiles would be limited. Therefore, even though impacts of asteroids and meteorites were frequent on the prebiotic Earth, impact events would not have significantly changed the ee of proteinogenic amino acids accumulated in the entire ocean.

  1. Geranylgeranylacetone prevents stress-induced decline of leptin secretion in mice.

    Science.gov (United States)

    Itai, Miki; Kuwano, Yuki; Nishikawa, Tatsuya; Rokutan, Kazuhito; Kensei, Nishida

    2018-01-01

    Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

  2. Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

    Science.gov (United States)

    Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

    2003-05-01

    Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance

  3. Ion-induced aerosol formation in a H20-H2S04 system

    International Nuclear Information System (INIS)

    Raes, F.; Janssens, A.

    1986-01-01

    The results of an experiment that was set up to demonstrate the occurrence of ion-induced aerosol formation (see Part I of this paper, Raes and Janssens, 1985) are analysed quantitatively by modelling the dynamics of aerosol formation and growth under different irradiation conditions. The model calculations indicate that ion-induced aerosol formation may contribute significantly to the total particle formation in a gas mixture that is simultaneously being irradiated with u.v. and γ irradiation. However, the measurements do not appear to be accurate enough to support these calculations. A qualitative comparison of the experiments with the calculations suggests that ion-induced nucleation is actually occurring in the experiments and that the classical theory of ion-induced aerosol formation may underestimate the actual rate of aerosol formation around ions. (author)

  4. An insert-based enzymatic cell culture system to rapidly and reversibly induce hypoxia: investigations of hypoxia-induced cell damage, protein expression and phosphorylation in neuronal IMR-32 cells

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2013-11-01

    Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. A semipermeable membrane insert system in combination with the hypoxia-inducing enzymes glucose oxidase and catalase was employed to rapidly and reversibly generate hypoxic conditions in the culture medium. Hydrogen peroxide assays, glucose measurements and western blotting were performed to validate the system and to evaluate the effects of the generated hypoxia on neuronal IMR-32 cells. Using the insert-based two-enzyme model, hypoxic conditions were rapidly induced in the culture medium. Glucose concentrations gradually decreased, whereas levels of hydrogen peroxide were not altered. Moreover, a rapid and reversible (onoff generation of hypoxia could be performed by the addition and subsequent removal of the enzyme-containing inserts. Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage. Hypoxic conditions also increased the amounts of cellular procaspase-3 and catalase as well as phosphorylation of the pro-survival kinase Akt, but not Erk1/2 or STAT5. In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. We claim that the model, the first of its kind, enables researchers to rapidly and

  5. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions

    International Nuclear Information System (INIS)

    Ren Hongying; Cao Ying; Zhao, Qinjun; Li Jing; Zhou Cixiang; Liao Lianming; Jia Mingyue; Zhao Qian; Cai Huiguo; Han Zhongchao; Yang Renchi; Chen Guoqiang; Zhao, R.C.

    2006-01-01

    Low oxygen tension is a potent differentiation inducer of numerous cell types and an effective stimulus of many gene expressions. Here, we described that under 8% O 2 , bone marrow stromal cells (MSCs) exhibited proliferative and morphologic changes. The level of differentiated antigen H-2Dd and the number of G 2 /S/M phase cells increased evidently under 8% O 2 condition. Also, the proportion of wide, flattened, and epithelial-like cells (which were alkaline phosphatase staining positive) in MSCs increased significantly. When cultured in adipogenic medium, there was a 5- to 6-fold increase in the number of lipid droplets under hypoxic conditions compared with that in normoxic culture. We also demonstrated the existence of MSC differentiation under hypoxic conditions by electron microscopy. Expression of Oct4 was inhibited under 8% O 2 condition, but after adipocyte differentiation in normoxic culture and hypoxia-mimicking agents cobalt chloride (CoCl 2 ) and deferoxamine mesylate (DFX) treatments, Oct4 was still expressed in MSCs. These results indicate hypoxia accelerates MSC differentiation and hypoxia and hypoxia-mimicking agents exert different effects on MSC differentiation

  6. Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.

    Directory of Open Access Journals (Sweden)

    Wei-Chun Huang

    Full Text Available Pulmonary arterial hypertension (PAH is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs and iPSC-conditioned medium (iPSC CM were explored in monocrotaline (MCT-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1β, IL-6, IL-12α, IL-12β, IL-23 and IFNγ genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-κB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-κB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF-κB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-κB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-κB phosphorylation.

  7. Does 3D produce more symptoms of visually induced motion sickness?

    Science.gov (United States)

    Naqvi, Syed Ali Arsalan; Badruddin, Nasreen; Malik, Aamir Saeed; Hazabbah, Wan; Abdullah, Baharudin

    2013-01-01

    3D stereoscopy technology with high quality images and depth perception provides entertainment to its viewers. However, the technology is not mature yet and sometimes may have adverse effects on viewers. Some viewers have reported discomfort in watching videos with 3D technology. In this research we performed an experiment showing a movie in 2D and 3D environments to participants. Subjective and objective data are recorded and compared in both conditions. Results from subjective reporting shows that Visually Induced Motion Sickness (VIMS) is significantly higher in 3D condition. For objective measurement, ECG data is recorded to find the Heart Rate Variability (HRV), where the LF/HF ratio, which is the index of sympathetic nerve activity, is analyzed to find the changes in the participants' feelings over time. The average scores of nausea, disorientation and total score of SSQ show that there is a significant difference in the 3D condition from 2D. However, LF/HF ratio is not showing significant difference throughout the experiment.

  8. The effect of post-welding conditions in friction stir welds: From weld simulation to Ductile Failure

    DEFF Research Database (Denmark)

    Hattel, Jesper Henri; Nielsen, Kim Lau; Tutum, Cem Celal

    2012-01-01

    software ANSYS, a thermo-mechanical model is employed to predict the thermally induced stresses and strains during welding, while an in-house finite element code is used to study the plastic flow localization and failure in a subsequent structural analysis. The coupling between the two models is made......The post-welding stress state, strain history and material conditions of friction stir welded joints are often strongly idealized when used in subsequent modeling analyses, typically by neglecting one or more of the features above. But, it is obvious that the conditions after welding do influence......, showed the largest influence of the post-welding conditions, even though significant relaxation of the residual stress state was predicted....

  9. Measurement of Survival Time in Brachionus Rotifers: Synchronization of Maternal Conditions.

    Science.gov (United States)

    Kaneko, Gen; Yoshinaga, Tatsuki; Gribble, Kristin E; Welch, David M; Ushio, Hideki

    2016-07-22

    Rotifers are microscopic cosmopolitan zooplankton used as models in ecotoxicological and aging studies due to their several advantages such as short lifespan, ease of culture, and parthenogenesis that enables clonal culture. However, caution is required when measuring their survival time as it is affected by maternal age and maternal feeding conditions. Here we provide a protocol for powerful and reproducible measurement of the survival time in Brachionus rotifers following a careful synchronization of culture conditions over several generations. Empirically, poor synchronization results in early mortality and a gradual decrease in survival rate, thus resulting in weak statistical power. Indeed, under such conditions, calorie restriction (CR) failed to significantly extend the lifespan of B. plicatilis although CR-induced longevity has been demonstrated with well-synchronized rotifer samples in past and present studies. This protocol is probably useful for other invertebrate models, including the fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans, because maternal age effects have also been reported in these species.

  10. Benzocaine-Induced Methemoglobinemia: A Condition of which all Endoscopists Should Be Aware

    Directory of Open Access Journals (Sweden)

    C Armstrong

    2004-01-01

    Full Text Available Methemoglobinemia is a rare complication that can occur with the use of benzocaine-containing compounds. Two cases of methemoglobinemia are reported, and the pathophysiology and treatment of methemoglobinemia are reviewed. Both patients received topical 20% benzocaine spray before endoscopy. Immediately following the procedure, there was a reduction in O2 saturation assessed by pulse oximetry that was refractory to O2 therapy. Dramatic peripheral and central cyanosis developed. O2 saturation measured by pulse oximetry ranged from 83% to 87% on O2 by nasal prongs and 100% O2 by a nonrebreathing mask. Both patients were mildly confused and one patient complained of a significant headache. The diagnosis of methemoglobinemia was considered and arterial blood gas sampling was performed. In both patients, the arterial blood had a chocolate brown colour. A methemoglobin level of 48% and 18% was noted in patient 1 and patient 2, respectively. Both patients were treated with methylene blue, resulting in a significant improvement with gradual normalization of their O2 saturation within 10 min to 30 min. The use of benzocaine spray may not markedly alter the patient's perception of endoscopy and thus, the routine use of these agents should be questioned. If such agents are used, the physician must be aware of this association to prevent a delay in the diagnosis and management of this rare, but potentially lethal, condition.

  11. Natural circulation cooling in a PWR geometry under accident-induced conditions

    International Nuclear Information System (INIS)

    Shimeck, D.J.; Johnsen, G.W.

    1983-01-01

    The characteristics and limits of natural circulation heat rejection over a wide range of conditions were experimentally investigated in a small-scale model of a pressurized water reactor. Conditions that were varied included primary and secondary coolant inventory, decay heat power, and primary noncondensable gas content. The results have defined three distinct modes of natural circulation, their limits and transition points, and the characteristic signatures accompanying natural circulation behavior. Particular emphasis is focused on the limits of natural circulation under severely degraded primary and secondary conditions

  12. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees......Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper...

  13. Extracellular histones induce erythrocyte fragility and anemia.

    Science.gov (United States)

    Kordbacheh, Farzaneh; O'Meara, Connor H; Coupland, Lucy A; Lelliott, Patrick M; Parish, Christopher R

    2017-12-28

    Extracellular histones have been shown to play an important pathogenic role in many diseases, primarily through their cytotoxicity toward nucleated cells and their ability to promote platelet activation with resultant thrombosis and thrombocytopenia. In contrast, little is known about the effect of extracellular histones on erythrocyte function. We demonstrate in this study that histones promote erythrocyte aggregation, sedimentation, and using a novel in vitro shear stress model, we show that histones induce erythrocyte fragility and lysis in a concentration-dependent manner. Furthermore, histones impair erythrocyte deformability based on reduced passage of erythrocytes through an artificial spleen. These in vitro results were mirrored in vivo with the injection of histones inducing anemia within minutes of administration, with a concomitant increase in splenic hemoglobin content. Thrombocytopenia and leukopenia were also observed. These findings suggest that histones binding to erythrocytes may contribute to the elevated erythrocyte sedimentation rates observed in inflammatory conditions. Furthermore, histone-induced increases in red blood cell lysis and splenic clearance may be a significant factor in the unexplained anemias seen in critically ill patients. © 2017 by The American Society of Hematology.

  14. Mixed martial arts induces significant fatigue and muscle damage up to 24 hours post-combat.

    Science.gov (United States)

    Ghoul, Nihel; Tabben, Montassar; Miarka, Bianca; Tourny, Claire; Chamari, Karim; Coquart, Jeremy

    2017-06-22

    This study investigates the physiological/physical responses to a simulated mixed martial arts (MMA) competition over 24 hr. Twelve fighters performed a simulated MMA competition, consisting of three 5-min MMA matches. Physiological/physical data were assessed before (Trest), directly after round 1 (Trd1), round 2 (Trd2) and round 3 (Trd3), and then 30-min (Trecovery30min) and/or 24-hr (Trecovery24h) post-competition. Heart rate (HR), rating of perceived exertion (RPE) and blood lactate concentration ([La]) were assessed at Trest, Trd1, Trd2 and Trd3. Biological data were collected at Trest, Trd3, Trecovery30min and Trecovery24h. Physical tests were performed at Trest, Trecovery30min and Trecovery24h. HR, RPE and [La] were high during competition. Leukocytes, hemoglobin, total protein and glycemia were increased at Trd3 compared with all other time points (p<0.05). Cortisol was increased at Trd3 compared with Trest and Trecovery24h (p<0.05). Testosterone was higher at Trd3 and Trecovery30min than Trest (p<0.001). Higher values of uric acid were noted during recovery periods (p<0.001). Lactate dehydrogenase was lower at Trest compared with Trd3, Trecovery30min and Trecovery24h (p<0.05). Countermovement jump was higher at Trest than Trecovery30min (p=0.020). Consequently, MMA is a high-intensity intermittent combat sport that induces significant fatigue and muscle damage, both of which are still present 24-hr post-competition.

  15. Small river plumes off the northeastern coast of the Black Sea under average climatic and flooding discharge conditions

    Science.gov (United States)

    Osadchiev, Alexander; Korshenko, Evgeniya

    2017-06-01

    This study focuses on the impact of discharges of small rivers on the delivery and fate of fluvial water and suspended matter at the northeastern part of the Black Sea under different local precipitation conditions. Several dozens of mountainous rivers flow into the sea at the study region, and most of them, except for several of the largest, have little annual runoff and affect adjacent coastal waters to a limited extent under average climatic conditions. However, the discharges of these small rivers are characterized by a quick response to precipitation events and can significantly increase during and shortly after heavy rains, which are frequent in the considered area. The delivery and fate of fluvial water and terrigenous sediments at the study region, under average climatic and rain-induced flooding conditions, were explored and compared using in situ data, satellite imagery, and numerical modeling. It was shown that the point-source spread of continental discharge dominated by several large rivers under average climatic conditions can change to the line-source discharge from numerous small rivers situated along the coast in response to heavy rains. The intense line-source runoff of water and suspended sediments forms a geostrophic alongshore current of turbid and freshened water, which induces the intense transport of suspended and dissolved constituents discharged with river waters in a northwestern direction. This process significantly influences water quality and causes active sediment load at large segments of the narrow shelf at the northeastern part of the Black Sea compared to average climatic discharge conditions.

  16. Small river plumes off the northeastern coast of the Black Sea under average climatic and flooding discharge conditions

    Directory of Open Access Journals (Sweden)

    A. Osadchiev

    2017-06-01

    Full Text Available This study focuses on the impact of discharges of small rivers on the delivery and fate of fluvial water and suspended matter at the northeastern part of the Black Sea under different local precipitation conditions. Several dozens of mountainous rivers flow into the sea at the study region, and most of them, except for several of the largest, have little annual runoff and affect adjacent coastal waters to a limited extent under average climatic conditions. However, the discharges of these small rivers are characterized by a quick response to precipitation events and can significantly increase during and shortly after heavy rains, which are frequent in the considered area. The delivery and fate of fluvial water and terrigenous sediments at the study region, under average climatic and rain-induced flooding conditions, were explored and compared using in situ data, satellite imagery, and numerical modeling. It was shown that the point-source spread of continental discharge dominated by several large rivers under average climatic conditions can change to the line-source discharge from numerous small rivers situated along the coast in response to heavy rains. The intense line-source runoff of water and suspended sediments forms a geostrophic alongshore current of turbid and freshened water, which induces the intense transport of suspended and dissolved constituents discharged with river waters in a northwestern direction. This process significantly influences water quality and causes active sediment load at large segments of the narrow shelf at the northeastern part of the Black Sea compared to average climatic discharge conditions.

  17. How significant is the ‘significant other’? Associations between significant others’ health behaviors and attitudes and young adults’ health outcomes

    Directory of Open Access Journals (Sweden)

    Berge Jerica M

    2012-04-01

    Full Text Available Abstract Background Having a significant other has been shown to be protective against physical and psychological health conditions for adults. Less is known about the period of emerging young adulthood and associations between significant others’ weight and weight-related health behaviors (e.g. healthy dietary intake, the frequency of physical activity, weight status. This study examined the association between significant others’ health attitudes and behaviors regarding eating and physical activity and young adults’ weight status, dietary intake, and physical activity. Methods This study uses data from Project EAT-III, a population-based cohort study with emerging young adults from diverse ethnic and socioeconomic backgrounds (n = 1212. Logistic regression models examining cross-sectional associations, adjusted for sociodemographics and health behaviors five years earlier, were used to estimate predicted probabilities and calculate prevalence differences. Results Young adult women whose significant others had health promoting attitudes/behaviors were significantly less likely to be overweight/obese and were more likely to eat ≥ 5 fruits/vegetables per day and engage in ≥ 3.5 hours/week of physical activity, compared to women whose significant others did not have health promoting behaviors/attitudes. Young adult men whose significant other had health promoting behaviors/attitudes were more likely to engage in ≥ 3.5 hours/week of physical activity compared to men whose significant others did not have health promoting behaviors/attitudes. Conclusions Findings suggest the protective nature of the significant other with regard to weight-related health behaviors of young adults, particularly for young adult women. Obesity prevention efforts should consider the importance of including the significant other in intervention efforts with young adult women and potentially men.

  18. Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

    Science.gov (United States)

    Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P

    2010-12-01

    Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.

  19. Effects of nicardipine on the onset time and intubation conditions of rocuronium-induced neuromuscular blockade.

    Science.gov (United States)

    Lee, Sun-Yeul; Kim, Yoon-Hee; Ko, Young-Kwon; Park, Sang-Il; Lee, Jung-Un; Chung, Woo-Suk; Lim, Chae-Seong

    2016-08-01

    The objective of this study was to identify the effects of nicardipine on neuromuscular blockade of rocuronium, such as the onset time and intubation conditions, using a nicardipine dose that attenuates cardiovascular responses during endotracheal intubation. Randomized, double-blinded, placebo-controlled clinical comparison was used as the design of this study The study was conducted at the operating room of a university hospital. Participants of this study comprise 78 American Society of Anesthesiologists physical status 1 and 2 patients, aged 18 to 60 years who were undergoing elective surgery under general anesthesia. The nicardipine group was given an intravenous bolus of 20 μg/kg nicardipine before tracheal intubation: the control group was given an intravenous bolus of a comparable volume of normal saline before tracheal intubation. Using a TOF-Watch SX monitor, the time from the end of the injection of rocuronium to maximum depression of T1 (onset time) was measured. Intubation was performed 1 minute after rocuronium administration, and the status of the intubation conditions was assessed. The mean blood pressure and heart rate were each measured after endotracheal intubation. Rate pressure product values were also calculated. Intubation conditions were clinically acceptable in 37 (94.9%) of 39 patients in group N compared with 29 (74.4%) of 39 in group C (P rocuronium was significantly faster in group N than in group C (P .05). Pretreatment with 20 μg/kg nicardipine improves intubation conditions, shortens the onset time of rocuronium, and attenuates cardiovascular responses to tracheal intubation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Electrical in situ and post-irradiation properties of ceramics relevant to fusion irradiation conditions

    International Nuclear Information System (INIS)

    Shikama, Tatsuo; Zinkle, S.J.

    2002-01-01

    Electrical properties of ceramic candidate materials for the next-generation nuclear fusion devices under relevant irradiation conditions are reviewed. A main focal point is placed on the degradation behavior of the electrical insulating ability during and after irradiation. Several important radiation induced effects play important roles: radiation induced conductivity, thermally stimulated electrical conductivity, radiation induced electrical charge separation, and radiation induced electromotive force. These phenomena will interact with each other under fusion relevant irradiation conditions. The design of electrical components for the next-generation fusion devices should take into account these complicated interactions among the radiation induced phenomena

  1. Air conditioning systems as non-infectious health hazards inducing acute respiratory symptoms.

    Science.gov (United States)

    Gerber, Alexander; Fischer, Axel; Willig, Karl-Heinz; Groneberg, David A

    2006-04-01

    Chronic and acute exposure to toxic aerosols belongs to frequent causes of airway diseases. However, asthma attacks due to long-distance inhalative exposure to organic solvents, transmitted via an air condition system, have not been reported so far. The present case illustrates the possibility of air conditioning systems as non-infectious health hazards in occupational medicine. So far, only infectious diseases such as legionella pneumophila pneumonia have commonly been associated to air-conditioning exposures but physicians should be alert to the potential of transmission of toxic volatile substances via air conditioning systems. In view of the events of the 11th of September 2001 with a growing danger of large building terrorism which may even use air conditioning systems to transmit toxins, facility management security staff should be alerted to possible non-infectious toxic health hazards arising from air-conditioning systems.

  2. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Science.gov (United States)

    Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior. PMID:26075223

  3. Chewing prevents stress-induced hippocampal LTD formation and anxiety-related behaviors: a possible role of the dopaminergic system.

    Science.gov (United States)

    Ono, Yumie; Koizumi, So; Onozuka, Minoru

    2015-01-01

    The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  4. Arabidopsis Phosphatidic Acid Phosphohydrolases Are Essential for Growth under Nitrogen-Depleted Conditions

    Directory of Open Access Journals (Sweden)

    Yushi Yoshitake

    2017-10-01

    Full Text Available The Arabidopsis homologs of mammalian lipin, PAH1 and PAH2, are cytosolic phosphatidic acid phosphohydrolases that are involved in phospholipid biosynthesis and are essential for growth under phosphate starvation. Here, pah1 pah2 double-knockout mutants were found to be hypersensitive to nitrogen (N starvation, whereas transgenic plants overexpressing PAH1 or PAH2 in the pah1 pah2 mutant background showed a similar growth phenotype as compared with wild type (WT under N starvation. The chlorophyll content of pah1 pah2 was significantly lower than that of WT, whereas the chlorophyll content and photosynthetic activity of the transgenic plants were significantly higher than those of WT under N-depleted conditions. Membrane glycerolipid composition of the pah1 pah2 mutants showed a significant decrease in the mole percent of chloroplast lipids to other phospholipids, whereas membrane lipid composition did not differ between transgenic plants and WT plants. Pulse-chase labeling experiments using plants grown under N-depleted conditions showed that, in pah1 pah2 plants, the labeling percent of chloroplast lipids such as phosphatidylglycerol and monogalactosyldiacylglycerol in the total glycerolipids was significantly lower than in WT. Moreover, N starvation-induced degradation of chloroplast structure was enhanced in pah1 pah2 mutants, and the membrane structure was recovered by complementation with PAH1. Thus, PAH is involved in maintaining chloroplast membrane structure and is required for growth under N-depleted conditions.

  5. Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

    Science.gov (United States)

    Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

    2015-01-01

    Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

  6. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

    Science.gov (United States)

    Azzopardi, David; Patel, Kharishma; Jaunky, Tomasz; Santopietro, Simone; Camacho, Oscar M.; McAughey, John; Gaça, Marianna

    2016-01-01

    Abstract Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm2) and nicotine (0.89 vs. 0.27 μg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products. PMID:27690199

  7. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Lee Na-Young

    2010-08-01

    Full Text Available Abstract Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells, as in vitro blood-placental barrier (BPB model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC activator in TR-TBT cells. Also, calcium ion (Ca2+ was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α, lipopolysaccharide (LPS and diethyl maleate (DEM significantly increased taurine uptake, but H2O2 and nitric oxide (NO donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus.

  8. Radiation conditions in the ring hall of the IHEP proton synchrotron

    International Nuclear Information System (INIS)

    Borodin, V.E.; Ermolenko, L.S.; Obryashchikova, L.P.

    1975-01-01

    The paper presents the results on studying the radiation conditions caused by induced radioactivity of the accelerator units in the ring hall. The data on the induced radioactivity level just on the ring vacuum chamber are reported. Radiation conditions in the most characteristic areas of the hall are considered. The changes in time of the dose rate at the internal target and at the entrance to the hall are shown

  9. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  10. Significance of aerophytotherapy in complex sanatorial-climatic treatment of patients with pneumoconiosis and dust-induced bronchitis

    Energy Technology Data Exchange (ETDEWEB)

    Ostapchuk, I.F.; Dubrovina, R.M.; Akimov, Yu.A.; Kalinina, T.F.; Protsko, G.V.; Kudzi, Eh.K.; Soboleva, O.S.

    1986-09-01

    Investigation is conducted to examine effectiveness of sanatorial-climatic treatment of patients with pneumoconiosis and dust-induced bronchitis while including aerophytotherapy. Patients with both lung diseases received sanatorial, gymnastic and climatic procedures. Experimental group also received aerophytotherapy - inhalation of ester oils of lavender, anise, mint, and salvia in form of spray corresponding to their molecular composition in air. Control group did not receive aerophytotherapy. Tables present results of experiment showing changes in parameters of external breathing in patients with pneumoconiosis and in patients with dust-induced bronchitis. Tables show greater improvement in characteristics of external breathing of patients treated with inclusion of aerophytotherapy and confirm effectiveness of combined sanatorial-climatic treatment with aerophytotherapy. Patients with chronic bronchitis also experienced reduction of bronchospasm and improvement in bronchial passability. Method does not require special equipment and is economical. 9 refs.

  11. Corona discharge induced snow formation in a cloud chamber.

    Science.gov (United States)

    Ju, Jingjing; Wang, Tie-Jun; Li, Ruxin; Du, Shengzhe; Sun, Haiyi; Liu, Yonghong; Tian, Ye; Bai, Yafeng; Liu, Yaoxiang; Chen, Na; Wang, Jingwei; Wang, Cheng; Liu, Jiansheng; Chin, S L; Xu, Zhizhan

    2017-09-18

    Artificial rainmaking is in strong demand especially in arid regions. Traditional methods of seeding various Cloud Condensation Nuclei (CCN) into the clouds are costly and not environment friendly. Possible solutions based on ionization were proposed more than 100 years ago but there is still a lack of convincing verification or evidence. In this report, we demonstrated for the first time the condensation and precipitation (or snowfall) induced by a corona discharge inside a cloud chamber. Ionic wind was found to have played a more significant role than ions as extra CCN. In comparison with another newly emerging femtosecond laser filamentation ionization method, the snow precipitation induced by the corona discharge has about 4 orders of magnitude higher wall-plug efficiency under similar conditions.

  12. Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis

    Science.gov (United States)

    Fan, Tingting; Zhang, Changsong; Zong, Ming; Fan, Lieying

    2018-01-01

    Impaired apoptosis of rheumatoid arthritis (RA)-fibroblast-like synoviocytes (FLS) is pivotal in the process of RA. Peptidyl arginine deiminase type IV (PADI4) is associated with autoantibody regulation via histone citrullination in RA. The present study aimed to investigate the role of PADI4 in the apoptosis of RA-FLS. FLS were isolated from patients with RA and a rat model. The effects of PADI4 on RA-FLS were investigated in vitro and in vivo. Hypoxia-induced autophagy was induced by 1% O2 and was detected by immunohistochemical and immunofluorescence analysis; in addition, apoptosis was detected by flow cytometry. RA-FLS obtained from RA rat model exhibited significant proliferation under severe hypoxia conditions. Hypoxia also significantly induced autophagy and elevated the expression of PADI4. Subsequently, short hairpin RNA-mediated PADI4 knockdown was demonstrated to significantly inhibit hypoxia-induced autophagy and promote apoptosis in RA-FLS. The results of these in vitro and in vivo studies suggested that PADI4 may be closely associated with hypoxia-induced autophagy, and the inhibition of hypoxia-induced autophagy by PADI4 knockdown may contribute to an increase in the apoptosis of RA-FLS. PMID:29393388

  13. Attention-induced deactivations in very low frequency EEG oscillations: differential localisation according to ADHD symptom status.

    Directory of Open Access Journals (Sweden)

    Samantha J Broyd

    Full Text Available BACKGROUND: The default-mode network (DMN is characterised by coherent very low frequency (VLF brain oscillations. The cognitive significance of this VLF profile remains unclear, partly because of the temporally constrained nature of the blood oxygen-level dependent (BOLD signal. Previously we have identified a VLF EEG network of scalp locations that shares many features of the DMN. Here we explore the intracranial sources of VLF EEG and examine their overlap with the DMN in adults with high and low ADHD ratings. METHODOLOGY/PRINCIPAL FINDINGS: DC-EEG was recorded using an equidistant 66 channel electrode montage in 25 adult participants with high- and 25 participants with low-ratings of ADHD symptoms during a rest condition and an attention demanding Eriksen task. VLF EEG power was calculated in the VLF band (0.02 to 0.2 Hz for the rest and task condition and compared for high and low ADHD participants. sLORETA was used to identify brain sources associated with the attention-induced deactivation of VLF EEG power, and to examine these sources in relation to ADHD symptoms. There was significant deactivation of VLF EEG power between the rest and task condition for the whole sample. Using s-LORETA the sources of this deactivation were localised to medial prefrontal regions, posterior cingulate cortex/precuneus and temporal regions. However, deactivation sources were different for high and low ADHD groups: In the low ADHD group attention-induced VLF EEG deactivation was most significant in medial prefrontal regions while for the high ADHD group this deactivation was predominantly localised to the temporal lobes. CONCLUSIONS/SIGNIFICANCE: Attention-induced VLF EEG deactivations have intracranial sources that appear to overlap with those of the DMN. Furthermore, these seem to be related to ADHD symptom status, with high ADHD adults failing to significantly deactivate medial prefrontal regions while at the same time showing significant attenuation of

  14. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

    2017-01-01

    Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

  15. Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development.

    Science.gov (United States)

    Tsuji, Kenji; Kitamura, Shinji; Makino, Hirofumi

    2014-04-25

    The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. In this study, we examined whether HIF regulates kidney development. We harvested kidneys from day 13 rat embryos (E13Ks) and cultured the organs under normoxic (20% O2/5% CO2) or hypoxic (5% O2/5% CO2) conditions. We evaluated the kidneys based on morphology and gene expression. E13Ks cultured under hypoxic conditions had significantly more ureteric bud (UB) branching than the E13Ks cultured under normoxic conditions. In addition, the mRNA levels of GDNF and GDNF receptor (GFR-α1), increased under hypoxic conditions in E13Ks. When we cultured E13Ks with the HIF-1α inhibitor digoxin or with siRNA targeting HIF-1α under hypoxic conditions, we did not observe increased UB branching. In addition, the expression of GDNF and GFR-α1 was inhibited under hypoxic conditions when the kidneys were treated with siRNA targeting HIF-1α. We also elucidated that hypoxia inhibited UB cell apoptosis and promoted the expression of FGF7 mRNA levels in metanephric mesenchymal (MM) cells in vitro. These findings suggest that hypoxic condition has important roles in inducing branching morphogenesis during kidney development. Hypoxia might mediate branching morphogenesis via not only GDNF/Ret but also FGF signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Flow-induced elastic anisotropy of metallic glasses

    International Nuclear Information System (INIS)

    Sun, Y.H.; Concustell, A.; Carpenter, M.A.; Qiao, J.C.; Rayment, A.W.; Greer, A.L.

    2016-01-01

    As-cast bulk metallic glasses are isotropic, but anisotropy can be induced by thermomechanical treatments. For example, the diffraction halo in the structure function S(Q) observed in transmission becomes elliptical (rather than circular) after creep in uniaxial tension or compression. Published studies associate this with frozen-in anelastic strain and bond-orientational anisotropy. Results so far are inconsistent on whether viscoplastic flow of metallic glasses can induce anisotropy. Preliminary diffraction data suggest that the anisotropy, if any, is very low, while measurements of the elastic properties suggest that there is induced anisotropy, opposite in sign to that due to anelastic strain. We study three bulk metallic glasses, Ce 65 Al 10 Cu 20 Co 5 , La 55 Ni 10 Al 35 , and Pd 40 Ni 30 Cu 10 P 20 . By using resonant ultrasound spectroscopy to determine the full elasticity tensor, the effects of relaxation and rejuvenation can be reliably separated from uniaxial anisotropy (of either sign). The effects of viscoplastic flow in tension are reported for the first time. We find that viscoplastic flow of bulk metallic glasses, particularly in tension, can induce significant anisotropy that is distinct from that associated with frozen-in anelastic strain. The conditions for inducing such anisotropy are explored in terms of the Weissenberg number (ratio of relaxation times for primary relaxation and for shear strain rate). There is a clear need for further work to characterize the structural origins of flow-induced anisotropy and to explore the prospects for improved mechanical and other properties through induced anisotropy.

  17. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    Science.gov (United States)

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Faye M. Drawnel

    2014-11-01

    Full Text Available Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.

  19. Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

    Science.gov (United States)

    Lindquist, Derick H

    2013-04-01

    Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. An organization of visual and auditory fear conditioning in the lateral amygdala.

    Science.gov (United States)

    Bergstrom, Hadley C; Johnson, Luke R

    2014-12-01

    Pavlovian fear conditioning is an evolutionary conserved and extensively studied form of associative learning and memory. In mammals, the lateral amygdala (LA) is an essential locus for Pavlovian fear learning and memory. Despite significant progress unraveling the cellular mechanisms responsible for fear conditioning, very little is known about the anatomical organization of neurons encoding fear conditioning in the LA. One key question is how fear conditioning to different sensory stimuli is organized in LA neuronal ensembles. Here we show that Pavlovian fear conditioning, formed through either the auditory or visual sensory modality, activates a similar density of LA neurons expressing a learning-induced phosphorylated extracellular signal-regulated kinase (p-ERK1/2). While the size of the neuron population specific to either memory was similar, the anatomical distribution differed. Several discrete sites in the LA contained a small but significant number of p-ERK1/2-expressing neurons specific to either sensory modality. The sites were anatomically localized to different levels of the longitudinal plane and were independent of both memory strength and the relative size of the activated neuronal population, suggesting some portion of the memory trace for auditory and visually cued fear conditioning is allocated differently in the LA. Presenting the visual stimulus by itself did not activate the same p-ERK1/2 neuron density or pattern, confirming the novelty of light alone cannot account for the specific pattern of activated neurons after visual fear conditioning. Together, these findings reveal an anatomical distribution of visual and auditory fear conditioning at the level of neuronal ensembles in the LA. Copyright © 2014. Published by Elsevier Inc.