Science.gov

Sample records for action possibly involving

  1. Antinociceptive action of Ocimum sanctum (Tulsi) in mice: possible mechanisms involved.

    PubMed

    Khanna, N; Bhatia, Jagriti

    2003-10-01

    The alcoholic leaf extract of Ocimum sanctum (OS, Tulsi) was tested for analgesic activity in mice. In the glacial acetic acid (GAA)-induced writhing test, OS (50, 100 mg/kg, i.p.; and 50, 100, 200 mg/kg, p.o.) reduced the number of writhes. OS (50, 100 mg/kg, i.p.) also increased the tail withdrawal latency in mice. Naloxone (1 mg/kg, i.p.), an opioid antagonist, and DSP-4 (50 mg/kg, i.p.), a central noradrenaline depletor, attenuated the analgesic effect of OS in both the experimental models, whereas, PCPA (300 mg/kg, i.p.), a serotonin synthesis inhibitor, potentiated the action of OS on tail flick response in mice. The results of our study suggest that the analgesic action of OS is exerted both centrally as well as peripherally and involves an interplay between various neurotransmitter systems. PMID:12963158

  2. Possible involvement of K+-conductance in the action of gamma-aminobutyric acid in the guinea-pig hippocampus.

    PubMed Central

    Inoue, M.; Matsuo, T.; Ogata, N.

    1985-01-01

    The mechanism underlying the action of gamma-aminobutyric acid (GABA) in the hippocampus was investigated using guinea-pig brain slices. GABA either superfused or applied directly by microiontophoresis produced a biphasic response in pyramidal cells, comprising hyperpolarizing and depolarizing components. When different concentrations of GABA were applied to the same neurone, the lower concentrations generally produced a hyperpolarization-predominant response, while higher concentrations resulted in a depolarization-predominant response. The depolarizing component of the response to GABA was augmented in a medium containing a low concentration of Cl-, relatively unaffected by a change in external K+ concentration, and blocked by picrotoxin (2 X 10(-5) M). The depolarizing response to GABA persisted in a Ca2+-free medium in which the concentration of Na+ was reduced to 13 mM. Combined application of low doses of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response to GABA and produced a relatively pure hyperpolarizing response. The reversal potential of this pharmacologically 'isolated' hyperpolarizing response to GABA was estimated, from the current-voltage relationships, to be about -90 mV and was the same as that of the hyperpolarization induced by baclofen. When the membrane was successively hyperpolarized by inward direct current (d.c.) injections, the reversal point of the 'pharmacologically isolated' hyperpolarizing response to GABA coincided with that of the post-burst hyperpolarization. Low concentrations of Cl- in the bathing medium had no noticeable effect on the hyperpolarizing component of the response to GABA, whereas it markedly increased the amplitude of the depolarizing component. These results suggest that the action of GABA in the hippocampus may involve an activation of K+ conductance. PMID:2413946

  3. Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.

    PubMed

    Watanabe, T; Yuki, S; Egawa, M; Nishi, H

    1994-03-01

    The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and prolonged survival time in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and energy failure in hemispheric embolization of rats. Postischemic treatment with MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate (maximal inhibition, 40.2%), but at 100 microM it did not influence O2- generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron-dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0 microM). These findings suggest that MCI-186 has potent anti-ischemic actions and that its mechanism may be closely associated with beneficial antioxidant activities. PMID:8138971

  4. Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

    PubMed Central

    Wang, Chen; Qiu, Wenying; Zheng, Yiqing; Li, Hui; Li, Yijia; Feng, Bing; Guo, Shu; Yan, Li; Cao, Ji-Min

    2013-01-01

    Cortisol, a member of glucocorticoids, could potentiate the action of catecholamine by a non-genomic mechanism. Although this permissive effect has been well appreciated in the anti-asthmatic medication, the underlying signaling pathway has remained mysterious. Here, we show that extraneuronal monoamine transporter (EMT), a membraneous reuptake transporter for circulating catecholamine clearance, is the direct target of cortisol in its permissive effect. We found that BSA-conjugated cortisol, which functions as a cortisol but cannot penetrate cell membrane, enhanced the spasmolytic effect of β-adrenoceptor agonist (isoprenaline) in histamine-sensitized tracheal spirals of guinea pigs, and pharmacological inhibition of EMT with famotidine was powerful enough to imitate the permissive action of cortisol. To our surprise, EMT protein expression was high in the chondrocytes of tracheal cartilage, but was undetectable in tracheal smooth muscle cells. The functionality of EMT was further confirmed with measurement of catecholamine uptake by tracheal chondrocytes. Moreover, cortisol-initiated membrane signaling could activate protein kinase C (PKC), which phosphorylates EMT and induces its internalization via a lipid raft-dependent pathway. Both of the mechanisms slow down the reuptake process by chondrocytes, leading to extracellular catecholamine accumulation and results in a more profound adrenergic signaling activation in tracheal smooth muscle cells. Thus, an EMT-centered pathway was proposed to explain the permissive action of cortisol. Collectively, our results highlight the role of EMT in the crosstalk between glucocorticoid and catecholamine. EMT may represent a promising target for adrenergic signaling modulation. PMID:24098439

  5. Actions of pinacidil at a reduced potassium concentration: a direct cardiac effect possibly involving the ATP-dependent potassium channel.

    PubMed

    Chi, L; Black, S C; Kuo, P I; Fagbemi, S O; Lucchesi, B R

    1993-02-01

    We investigated the effects of the ATP-dependent K+ channel antagonist glyburide and the ATP-dependent K+ channel agonist pinacidil in a Langendorff-perfused rabbit isolated heart subjected to a period of global hypoxia. A class III antiarrhythmic drug, E-4031, also was studied in this model. These studies aimed to define the mechanism of action of putative profibrillatory actions of pinacidil and the mechanism for the antifibrillatory effect of the class III antiarrhythmic drug, E-4031, in the hypoxic heart. After stabilization and determination of baseline functional parameters under normoxic perfusion conditions (95% O2/5% CO2), hearts were subjected to global hypoxia by switching to a 95% N2/5% CO2 saturated perfusion medium for a period of 12 min. After the hypoxic period, normoxia was re-established by switching to the oxygen-carbon dioxide saturated buffer medium for a period of 40 min. The oxygen tension of the perfusion buffer was reduced from approximately 400 mm Hg to below 50 mm Hg during the hypoxic period. All hearts subjected to hypoxia had reduced function: the left ventricular developed pressure and +/- dP/dt were reduced significantly. Myocardial tissue ATP concentrations were reduced (> 50%) in hearts subjected to hypoxia. Under conditions of hypoxic/reoxygenation and in the presence of a low (2.5 mM) potassium concentration ([K+]0), pinacidil (1.25 microM) facilitated the induction of ventricular fibrillation (80% fibrillation in the presence of pinacidil vs. 20% in the absence of pinacidil). Glyburide (10 microM) and E-4031 (1 and 10 microM) significantly reduced the incidence of ventricular fibrillation associated with pinacidil (20% fibrillation in the presence of hypoxia, pinacidil, and glyburide or 10 microM E-4031). Opening of the ATP-dependent K+ channel by pinacidil under normoxia and low K+ also facilitated the induction of ventricular fibrillation (60% ventricular fibrillation). Pinacidil failed to induce ventricular fibrillation under

  6. Anxiolytic-like actions of the hexane extract from leaves of Annona cherimolia in two anxiety paradigms: possible involvement of the GABA/benzodiazepine receptor complex.

    PubMed

    López-Rubalcava, C; Piña-Medina, B; Estrada-Reyes, R; Heinze, G; Martínez-Vázquez, M

    2006-01-11

    A hexane extract of leaves of Annona cherimolia produced anxiolytic-like actions when administered to mice and tested in two animal models of anxiety: the mouse avoidance exploratory behavior and the burying behavior tests. In order to discard unspecific drug-actions on general activity, all treatments studied in the anxiety paradigms were also analyzed in the open field test. Results showed that A. cherimolia induced anxiolytic-like actions at the doses of 6.25, 12.5, 25.0 and 50.0 mg/kg. Picrotoxin (0.25 mg/kg), a GABA-gated chloride ion channel blocker, antagonized the anxiolytic-like actions of A. cherimolia, while a sub-effective dose of muscimol (0.5 mg/kg), a selective GABA(A) receptor agonist, facilitated the effects of a sub-optimal dose of A. cherimolia (3.12 mg/kg). Thus, the involvement of the GABA(A) receptor complex in the anxiolytic-like actions of A. cherimolia hexane extract is suggested. In addition the extract was also able to enhance the duration of sodium pentobarbital induced sleeping time. Taken together, results indicate that the hexane extract of A. cherimolia has depressant activity on the Central Nervous System and could interact with the GABA(A) receptor complex. On the other hand, the chromatographic separation of this extract led to the isolation of palmitone, and beta-sitosterol as major constituents. In addition a GC-MS study of some fractions revealed the presence of several compounds such beta-cariophyllene, beta-selinene, alpha-cubebene, and linalool that have been reported to show effects on behavior that could explain some of the extract effects. PMID:16122763

  7. In vitro screening of major neurotransmitter systems possibly involved in the mechanism of action of antibodies to S100 protein in released-active form

    PubMed Central

    Gorbunov, Evgeniy A; Ertuzun, Irina A; Kachaeva, Evgeniya V; Tarasov, Sergey A; Epstein, Oleg I

    2015-01-01

    Experimentally and clinically, it was shown that released-active form of antibodies to S100 protein (RAF of Abs to S100) exerts a wide range of pharmacological activities: anxiolytic, antiasthenic, antiaggressive, stress-protective, antihypoxic, antiischemic, neuroprotective, and nootropic. The purpose of this study was to determine the influence of RAF of Abs to S100 on major neurotransmitter systems (serotoninergic, GABAergic, dopaminergic, and on sigma receptors as well) which are possibly involved in its mechanism of pharmacological activity. Radioligand binding assays were used for assessment of the drug influence on ligand–receptor interaction. [35S]GTPγS binding assay, cyclic adenosine monophosphate HTRF™, cellular dielectric spectroscopy assays, and assays based on measurement of intracellular concentration of Ca2+ ions were used for assessment of agonist or antagonist properties of the drug toward receptors. RAF of Abs to S100 increased radioligand binding to 5-HT1F, 5-HT2B, 5-HT2Cedited, 5-HT3, and to D3 receptors by 142.0%, 131.9%, 149.3%, 120.7%, and 126.3%, respectively. Also, the drug significantly inhibited specific binding of radioligands to GABAB1A/B2 receptors by 25.8%, and to both native and recombinant human sigma1 receptors by 75.3% and 40.32%, respectively. In the functional assays, it was shown that the drug exerted antagonism at 5-HT1B, D3, and GABAB1A/B2 receptors inhibiting agonist-induced responses by 23.24%, 32.76%, and 30.2%, respectively. On the contrary, the drug exerted an agonist effect at 5-HT1A receptors enhancing receptor functional activity by 28.0%. The pharmacological profiling of RAF of Abs to S100 among 27 receptor provides evidence for drug-related modification of major neurotransmitter systems. PMID:26604768

  8. Possible involvement of phospholipase C and protein kinase C in stimulatory actions of L-leucine and its keto acid, alpha-ketoisocaproic acid, on protein synthesis in RLC-16 hepatocytes.

    PubMed

    Yagasaki, Kazumi; Morisaki-Tsuji, Naoko; Miura, Atsuhito; Funabiki, Ryuhei

    2002-11-01

    Effects of leucine and related compounds on protein synthesis were studied in RLC-16 hepatocytes. The incorporation of [(3)H] tyrosine into cellular protein was measured as an indexof protein synthesis. In leucine-depleted RLC-16 cells, L-leucineand its keto acid, alpha-ketoisocaproic acid (KIC), stimulated protein synthesis, while D-leucine did not. Mepacrine, an inhibitor of both phospholipase A(2) and C canceled stimulatory actions of L-leucine and KIC on protein synthesis, suggesting a possible involvement of either arachidonic acid metabolism by phospholipase A(2), cyclooxygenase or lipoxygenase, or phosphatidylinositol degradation by phospholipase C in the stimulatory actions of L-leucine and KIC.Neither indomethacin, an inhibitor of cyclooxygenase, nor caffeic acid, an inhibitor of lipoxygenase, diminished their stimulatory actions, suggesting no involvement of arachidonic acid metabolism. Conversely, 1-O-hexadecyl-2-O-methylglycerol, an inhibitor of protein kinase C, significantly canceled the stimulatory actions of L-leucine and KIC on protein synthesis, suggesting an involvement of phosphatidylinositol degradation and activation of protein kinase C. These results strongly suggest that both L-leucine and KIC stimulate protein synthesis in RLC-16 cells via activation of phospholipase C and production of diacylglycerol and inositol triphosphate from phosphatidylinositol, which in turn activate protein kinase C. PMID:19003115

  9. Possible Involvement of the Inhibition of NF-κB Factor in Anti-Inflammatory Actions That Melatonin Exerts on Mast Cells.

    PubMed

    Maldonado, M D; García-Moreno, H; González-Yanes, C; Calvo, J R

    2016-08-01

    Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL-2H3). It exhibits immunomodulatory, anti-inflammatory and anti-apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti-inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL-2H3 were pre-treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12-myristate 13-acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre-treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF-α and IL-6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF-κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down-regulation of mast cell activation. J. Cell. Biochem. 117: 1926-1933, 2016. © 2016 Wiley Periodicals, Inc. PMID:26756719

  10. Comprehension of action negation involves inhibitory simulation.

    PubMed

    Foroni, Francesco; Semin, Gün R

    2013-01-01

    Previous research suggests that action language is comprehended by activating the motor system. We report a study, investigating a critical question in this research field: do negative sentences activate the motor system? Participants were exposed to sentences in the affirmation and negation forms while the zygomatic muscle activity on the left side of the face was continuously measured (Electromyography technique: EMG). Sentences were descriptions of emotional expressions that mapped either directly upon the zygomatic muscle (e.g., "I am smiling") or did not (e.g., "I am frowning"). Reading sentences involving the negation of the activity of a specific muscle (zygomatic major-"I am not smiling") is shown to lead to the inhibition of this muscle. Reading sentences involving the affirmative form instead ("I am smiling") leads to the activation of zygomatic mucle. In contrast, sentences describing an activity that is irrelevant to the zygomatic muscle (e.g., "I am frowning" or "I am not frowning") produce no muscle activity. These results extend the range of simulation models to negation and by implication to an abstract domain. We discuss how this research contributes to the grounding of abstract and concrete concepts. PMID:23754996

  11. [A doctor's action within possible crime scene].

    PubMed

    Sowizdraniuk, Joanna

    2016-01-01

    Every doctor regardless of specialization in his practice may meet the need to provide assistance to victims of crime-related action. In this article there were disscused the issues of informing the investigative authorities about the crime, ensuring the safety of themselves and the environment at the scene. It also shows the specific elements of necessary procedures and practice to deal with the victims designed to securing any evidence present of potential or committed crime in proper manner. Special attention has been given to medical operation and other, necessary in case of certain criminal groups, among the latter we need to underline: actions against sexual freedom and decency, bodily integrity, life and well-being of human, and specially homicide, infanticide and suicide. PMID:27164285

  12. Principle of least action; some possible generalizations

    SciTech Connect

    Broucke, R.

    1982-08-01

    In this article we draw the attention to an important variational principle in dynamics: the Maupertuis-Jacobi Least Action Principle (MJLAP). This principle compares varied paths with the same energy h. We give two new proofs of the MJLAP (Sections 3 and 8) as well as a new unified variational principle which contains both Hamilton's Principle (HP) and the MJLAP as particular cases (Sections 4 and 9). The article also shows several new methods for the construction of a Lagrangian for a conservative dynamical system. As an example, we illustrate the theory with the classical Harmonic Oscillator Problem (Section 10). Our method is based on the theory of changes of independent variables in a dynamical system. It indirectly shows how a change of independent variable affects the self-adjointness of a dynamical system (Sections 5, 6, 7). Our new Lagrangians contain an arbitrary constant ..cap alpha.., whose meaning needs to be studied, eventually in relation to the concepts of quantification or gauge transformations. The two important values of the constant ..cap alpha.. are 1 (Hamilton's principle) and 1/2 (Maupertuis-Jacobi Least Action Principle).

  13. Factors that affect action possibility judgements: recent experience with the action and the current body state.

    PubMed

    Chandrasekharan, Sanjay; Binsted, Gordon; Ayres, Fabio; Higgins, Laura; Welsh, Timothy N

    2012-01-01

    It has been suggested that action possibility judgements are formed through a covert simulation of the to-be-executed action. We sought to determine whether the motor system (via a common coding mechanism) influences this simulation, by investigating whether action possibility judgements are influenced by experience with the movement task (Experiments 1 and 2) and current body states (Experiment 3). The judgement task in each experiment involved judging whether it was possible for a person's hand to accurately move between two targets at presented speeds. In Experiment 1, participants completed the action judgements before and after executing the movement they were required to judge. Results were that judged movement times after execution were closer to the actual execution time than those prior to execution. The results of Experiment 2 suggest that the effects of execution on judgements were not due to motor activation or perceptual task experience-alternative explanations of the execution-mediated judgement effects. Experiment 3 examined how judged movement times were influenced by participants wearing weights. Results revealed that wearing weights increased judged movement times. These results suggest that the simulation underlying the judgement process is connected to the motor system, and that simulations are dynamically generated, taking into account recent experience and current body state. PMID:22348464

  14. 4 CFR 28.140 - Personnel actions involving SES members.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Personnel actions involving SES members. 28.140 Section... ACCOUNTABILITY OFFICE Appeals by Members of the Senior Executive Service § 28.140 Personnel actions involving SES members. Members of the GAO Senior Executive Service (SES) may appeal adverse actions relating...

  15. GHB for cataplexy: Possible mode of action.

    PubMed

    Szabadi, Elemer

    2015-06-01

    The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (γ-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to 'heterologous denervation supersensitivity' resulting from the loss/weakening of the orexinergic input to the LC. This would lead to the sensitization of the autoinhibition mechanism of LC neurones mediated by inhibitory alpha-2 adrenoceptors ('autoreceptors'). Thus the excitatory input from the amygdala to the LC, activated by an emotional stimulus, would lead to the 'switching off' of LC activity via the supersensitive auto-inhibition mechanism. GHB is an agonist at both γ-aminobutyric acid (GABA) GABA (B) and GHB receptors that may be a subtype of an extrasynaptic GABA(A) receptor. GHB may prevent a cataplectic attack by dampening the tone of LC neurones via the stimulation of inhibitory extrasynaptic GABA receptors in the LC, and thus increasing the threshold for autoinhibition. PMID:25735989

  16. 40 CFR 300.525 - State involvement in removal actions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... accordance with § 300.415 on removal actions, and 40 CFR part 35, subpart O. (b) States are not required... 40 Protection of Environment 28 2011-07-01 2011-07-01 false State involvement in removal actions... POLLUTION CONTINGENCY PLAN State Involvement in Hazardous Substance Response § 300.525 State involvement...

  17. The influence of action possibility and end-state comfort on motor imagery of manual action sequences.

    PubMed

    Seegelke, Christian; Hughes, Charmayne M L

    2015-12-01

    It has been proposed that the preparation of goal-direct actions involves internal movement simulation, or motor imagery. Evidence suggests that motor imagery is critically involved in the prediction of action consequences and contributes heavily to movement planning processes. The present study examined whether the sensitivity towards end-state comfort and the possibility/impossibility to perform an action sequence are considered during motor imagery. Participants performed a mental rotation task in which two images were simultaneously presented. The image on the left depicted the start posture of a right hand when grasping a bar, while the right image depicted the hand posture at the end of the action sequence. The right image displayed the bar in a vertical orientation with the hand in a comfortable (thumb-up) or in an uncomfortable (thumb-down) posture, while the bar in the left image was rotated in picture plane in steps of 45°. Crucially, the two images formed either a physically possible or physically impossible to perform action sequence. Results revealed strikingly different response time patterns for the two action sequence conditions. In general, response times increased almost monotonically with increasing angular disparity for the possible to perform action sequences. However, slight deviations from this monotonicity were apparent when the sequences contained an uncomfortable as opposed to a comfortable final posture. In contrast, for the impossible sequences, response times did not follow a typical mental rotation function, but instead were uniformly very slow. These findings suggest that both biomechanical constraints (i.e., end-state comfort) and the awareness of the possibility/impossibility to perform an action sequence are considered during motor imagery. We conclude that motor representations contain information about the spatiotemporal movement organization and the possibility of performing an action, which are crucially involved in

  18. Joint action modulates motor system involvement during action observation in 3-year-olds.

    PubMed

    Meyer, Marlene; Hunnius, Sabine; van Elk, Michiel; van Ede, Freek; Bekkering, Harold

    2011-06-01

    When we are engaged in a joint action, we need to integrate our partner's actions with our own actions. Previous research has shown that in adults the involvement of one's own motor system is enhanced during observation of an action partner as compared to during observation of an individual actor. The aim of this study was to investigate whether similar motor system involvement is present at early stages of joint action development and whether it is related to joint action performance. In an EEG experiment with 3-year-old children, we assessed the children's brain activity and performance during a joint game with an adult experimenter. We used a simple button-pressing game in which the two players acted in turns. Power in the mu- and beta-frequency bands was compared when children were not actively moving but observing the experimenter's actions when (1) they were engaged in the joint action game and (2) when they were not engaged. Enhanced motor involvement during action observation as indicated by attenuated sensorimotor mu- and beta-power was found when the 3-year-olds were engaged in the joint action. This enhanced motor activation during action observation was associated with better joint action performance. The findings suggest that already in early childhood the motor system is differentially activated during action observation depending on the involvement in a joint action. This motor system involvement might play an important role for children's joint action performance. PMID:21479943

  19. Collaborative Action Research Involving Fiji and Solomon Islands Teachers.

    ERIC Educational Resources Information Center

    Singh, Gurmit

    2000-01-01

    Reviews the Basic Education and Life Skills program, which involves University of the South Pacific member countries, highlighting teacher involvement in collaborative action research to promote professional development at the school level. The paper describes the nature of teachers' involvement and shares insights from their experiences as…

  20. 5 CFR 9701.709 - Actions involving discrimination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....709 Section 9701.709 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM (DEPARTMENT OF HOMELAND SECURITY-OFFICE OF PERSONNEL MANAGEMENT) DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM Appeals § 9701.709 Actions involving discrimination....

  1. Environmental Volunteers: Factors Influencing Their Involvement in Environmental Action

    ERIC Educational Resources Information Center

    Liarakou, Georgia; Kostelou, Eleni; Gavrilakis, Costas

    2011-01-01

    The aim of the present study was to investigate the factors that influence volunteers to become involved in environmental action. The research focused on volunteers undertaking action in summer camps organised by an environmental non-governmental organisation (NGO) in Greece. The results suggest that the environmental issues addressed in volunteer…

  2. Hair follicle biology and topical minoxidil: possible mechanisms of action.

    PubMed

    Headington, J T

    1987-01-01

    The mechanism by which minoxidil, whether given orally or applied topically, stimulates hair growth remains undetermined. Possible indirect drug action, such as vasodilatation and increased blood flow to the dermal papilla, or possible local irritation related to minoxidil or to one or more components of the vehicle used for topical application has been suggested. Possible sites of direct drug action include either the dermal papilla of the follicle or hair matrix cells or possibly both. Morphometric studies of control scalp biopsies taken from young male patients with androgenetic alopecia reveal that the primary morphologic event in androgenetic alopecia is miniaturization of terminal hair follicles. Shortening and diminution of follicle size is undoubtedly accompanied by shortening of the hair growth cycle (decreased anagen time). Morphometric evaluation of scalp biopsies of patients receiving topical minoxidil in a vehicle composed of propylene glycol, water and ethanol has revealed growth of larger normally formed follicles when compared with pretreatment biopsies from the same individual. There has been no suggestion in any morphologic studies of minoxidil-treated patients for development of new follicles (follicular neogenesis). Because the dermal papilla of the hair follicle apparently controls both growth and differentiation of hair matrix cells and because there are no observable dysplastic or atypical changes in follicular germinal epithelium during or after application of topical minoxidil, it is concluded that the most probable site for the action of minoxidil is on the specialized mesenchymal cells of the follicular dermal papilla. PMID:3319729

  3. Computations involving differential operators and their actions on functions

    NASA Technical Reports Server (NTRS)

    Crouch, Peter E.; Grossman, Robert; Larson, Richard

    1991-01-01

    The algorithms derived by Grossmann and Larson (1989) are further developed for rewriting expressions involving differential operators. The differential operators involved arise in the local analysis of nonlinear dynamical systems. These algorithms are extended in two different directions: the algorithms are generalized so that they apply to differential operators on groups and the data structures and algorithms are developed to compute symbolically the action of differential operators on functions. Both of these generalizations are needed for applications.

  4. Alpha adrenoceptor subtypes involved in the emetic action in dogs.

    PubMed

    Hikasa, Y; Ogasawara, S; Takase, K

    1992-05-01

    In order to assess the involvement of alpha-1 and alpha-2 adrenoceptors in emesis, the emetic effect of eight alpha agonists was studied in dogs. The i.m. administration of each agonist elicited dose-dependent emesis. The order of potency in inducing emesis was: clonidine greater than oxymetazoline greater than tramazoline greater than naphazoline greater than xylazine greater than epinephrine greater than methoxamine = phenylephrine. The clonidine-induced emesis was antagonized by adrenoceptor antagonists showing alpha-2 blocking activity, yohimbine, tolazoline and phentolamine. Among these antagonists, yohimbine was the most effective. The alpha-1 and beta adrenergic, cholinergic, dopaminergic, histaminergic, serotonergic and opioid receptor antagonists did not prevent the clonidine-induced emesis. The emesis induced by oxymetazoline, tramazoline, xylazine, naphazoline and epinephrine was also antagonized by a selective alpha-2 adrenoceptor antagonist, yohimbine, but not by a selective alpha-1 adrenoceptor antagonist, prazosin. In contrast, methoxamine and phenylephrine-induced emesis was antagonized by prazosin, but not by yohimbine. Neither yohimbine nor prazosin prevented the morphine- and histamine-induced emesis. These results indicate that alpha-2 adrenoceptors are involved in the mediation of emetic action, and that the alpha adrenoceptor-mediated emesis does not involve beta adrenergic, cholinergic, dopaminergic, histaminergic, serotonergic and opioid receptors in the emetic pathway. This study further suggests that alpha adrenoceptors involved in the emesis are mainly of the alpha-2 type, although the involvement of alpha-1 adrenoceptors cannot be ruled out. PMID:1349647

  5. Evidence suggesting possible SCA1 gene involvement in schizophrenia

    SciTech Connect

    Diehl, S.R.; Wange, S.; Sun, C.

    1994-09-01

    Several findings suggest a possible role for the SCA1 gene on chromosome 6p in some cases of schizophrenia. First, linkage analyses in Irish pedigrees provided LOD scores up to 3.0 for one model tested using microsatellites closely linked to SCA1. Reanalysis of these data using affected sibpair methods yielded a significant result (p = 0.01) for one marker. An attempt to replicate this linkage finding was made using 44 NIMH families (206 individuals, 80 affected) and 12 Utah families (120 individuals, 49 affected). LOD scores were negative in these new families, even allowing for heterogeneity, as were results using affected sibpair methods. However, one Utah family provided a LOD score of 1.3. We also screened the SCA1 trinucleotide repeat to search for expansions characteristic of this disorder in these families and in 38 additional unrelated schizophrenics. We found 1 schizophrenic with 41 repeats, which is substantially larger than the maximum size of 36 repeats observed in previous studies of several hundred controls. We are now assessing whether the distribution of SCA1 repeats differs significantly in schizophrenia versus controls. Recent reports suggest possible anticipation in schizophrenia (also characteristic of SCA1) and a few cases of psychiatric symptoms suggesting schizophrenia have been observed in the highly related disorder DRPLA (SCA2), which is also based on trinucleotide repeat expansion. These findings suggest that further investigations of this gene and chromosome region may be a priority.

  6. Various Possible Toxicants Involved in Thyroid Dysfunction: A Review

    PubMed Central

    Bajaj, Jagminder K.; Salwan, Poonam

    2016-01-01

    About 300 million people across the world suffer from thyroid gland dysfunction. Environmental factors play an important role in causation of autoimmune thyroid diseases in susceptible individuals. Genetics contributes to 70% of the risk. In order to reduce the risk, we need to understand the association of environmental agents with thyroid dysfunction. These factors are especially relevant for those at increased risk due to positive family history. The ideal study to see the impact of a thyroid toxicant consists of directly measuring the degree of exposure to toxicant in an individual with his thyroid status. Knowledge of various factors influencing thyroid dysfunction can help in interpreting the results of such studies in a better way. This article is an attempt to highlight the various possible toxicants affecting thyroid function so that adequate measures can be undertaken to control excessive exposure in future to reduce the prevalence of thyroid disorders. PMID:26894086

  7. Various Possible Toxicants Involved in Thyroid Dysfunction: A Review.

    PubMed

    Bajaj, Jagminder K; Salwan, Poonam; Salwan, Shalini

    2016-01-01

    About 300 million people across the world suffer from thyroid gland dysfunction. Environmental factors play an important role in causation of autoimmune thyroid diseases in susceptible individuals. Genetics contributes to 70% of the risk. In order to reduce the risk, we need to understand the association of environmental agents with thyroid dysfunction. These factors are especially relevant for those at increased risk due to positive family history. The ideal study to see the impact of a thyroid toxicant consists of directly measuring the degree of exposure to toxicant in an individual with his thyroid status. Knowledge of various factors influencing thyroid dysfunction can help in interpreting the results of such studies in a better way. This article is an attempt to highlight the various possible toxicants affecting thyroid function so that adequate measures can be undertaken to control excessive exposure in future to reduce the prevalence of thyroid disorders. PMID:26894086

  8. Action Learning: The Possibility of Differing Hierarchies in Learning Sets

    ERIC Educational Resources Information Center

    Yeadon-Lee, Annie

    2013-01-01

    This paper presents the proposition that a variety of differing hierarchies exist in an action learning set at any one time, and each hierarchy has the potential to affect an individual's behaviour within the set. An interpretivist philosophy underpins the research framework adopted in this paper. Data were captured by means of 11 in-depth…

  9. An Action Learning Project on Diversity: Pitfalls and Possibilities.

    ERIC Educational Resources Information Center

    Hite, Linda M.

    1997-01-01

    In a college course on diversity in the workplace, students' experiences with conducting a cultural audit of the university as a workplace illustrate the dilemmas that can arise when students conduct action research in a real client system. Despite the inherent problems, the project resulted in significant student learning about the subject and…

  10. 10 CFR 26.77 - Management actions regarding possible impairment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Section 26.77 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Management Actions and... competently perform his or her duties. (b) If an individual appears to be impaired or the individual's fitness... perform drug and alcohol tests or implement the determination of fitness process otherwise required...

  11. 10 CFR 26.77 - Management actions regarding possible impairment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 26.77 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Management Actions and... competently perform his or her duties. (b) If an individual appears to be impaired or the individual's fitness... perform drug and alcohol tests or implement the determination of fitness process otherwise required...

  12. 10 CFR 26.77 - Management actions regarding possible impairment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Section 26.77 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Management Actions and... competently perform his or her duties. (b) If an individual appears to be impaired or the individual's fitness... perform drug and alcohol tests or implement the determination of fitness process otherwise required...

  13. 10 CFR 26.77 - Management actions regarding possible impairment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Section 26.77 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Management Actions and... competently perform his or her duties. (b) If an individual appears to be impaired or the individual's fitness... perform drug and alcohol tests or implement the determination of fitness process otherwise required...

  14. 10 CFR 26.77 - Management actions regarding possible impairment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Section 26.77 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Management Actions and... competently perform his or her duties. (b) If an individual appears to be impaired or the individual's fitness... perform drug and alcohol tests or implement the determination of fitness process otherwise required...

  15. Husband and wife with sarcoidosis: possible environmental factors involved

    PubMed Central

    2013-01-01

    Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that involves any organ, most commonly the lung and the lymph nodes. It is hypothesized that the disease derives from the interaction between single or multiple environmental factors and genetically determined host factors. Multiple potential etiologic agents for sarcoidosis have been proposed without any definitive demonstration of causality. We report the case of two patients, husband (57 years old) and wife (55 years old), both suffering from sarcoidosis. They underwent a lymph node biopsy by mediastinoscopy which showed a “granulomatous epithelioid giant cell non-necrotising chronic lymphadenitis”. They had lived up to 3 years ago in the country in a farm, in contact with organic dusts, animals such as dogs, chickens, rabbits, pigeons; now they have lived since about 3 years in an urban area where there are numerous chemical industries and stone quarries. The aim of this case report was to focus on environmental factors that might be related to the pathogenesis of the sarcoidosis. PMID:23351275

  16. 40 CFR 300.525 - State involvement in removal actions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... accordance with § 300.415 on removal actions, and 40 CFR part 35, subpart O. (b) States are not required under section 104(c)(3) of CERCLA to share in the cost of a Fund-financed removal action, unless the... disposal of hazardous substances therein and a Fund-financed remedial action is ultimately undertaken...

  17. 40 CFR 300.525 - State involvement in removal actions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... accordance with § 300.415 on removal actions, and 40 CFR part 35, subpart O. (b) States are not required under section 104(c)(3) of CERCLA to share in the cost of a Fund-financed removal action, unless the... disposal of hazardous substances therein and a Fund-financed remedial action is ultimately undertaken...

  18. 40 CFR 300.525 - State involvement in removal actions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... accordance with § 300.415 on removal actions, and 40 CFR part 35, subpart O. (b) States are not required under section 104(c)(3) of CERCLA to share in the cost of a Fund-financed removal action, unless the... disposal of hazardous substances therein and a Fund-financed remedial action is ultimately undertaken...

  19. 40 CFR 300.525 - State involvement in removal actions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... accordance with § 300.415 on removal actions, and 40 CFR part 35, subpart O. (b) States are not required under section 104(c)(3) of CERCLA to share in the cost of a Fund-financed removal action, unless the... disposal of hazardous substances therein and a Fund-financed remedial action is ultimately undertaken...

  20. Anxiolytic action of neuromedin-U and neurotransmitters involved in mice.

    PubMed

    Telegdy, G; Adamik, A

    2013-09-10

    Peptide Neuromedin-U (NmU) is widely distributed in the central nervous system and the peripheral tissues. Its physiological effects include the regulation of blood pressure, heart rate, and body temperature, and the inhibition of gastric acid secretion. The action of NmU in rats is mediated by two G-protein-coupled receptors, NmU-1R and NmU-2R. NmU-2R is present mainly in the brain, and NmU-1R mainly in the periphery. Despite the great variety of the physiological action of NmU, little is known about its possible effects in different forms of behavior, such as anxiety. In the present work, NmU-23 (the rodent form of the peptide) was tested for its effect on anxiety in elevated plus maze test in mice. For detection of the possible involvement of neurotransmitters, the mice were pretreated with receptor blockers: haloperidol (a D2, dopamine receptor antagonist), propranolol (a β-adrenergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine receptor antagonist), phenoxybenzamine (a nonselective α-adrenergic receptor antagonist) or nitro-l-arginine (a nitric oxide synthase inhibitor). The peptide and nitro-l-arginine were administered into the lateral brain ventricle, while the receptor blockers were applied intraperitoneally. An NmU-23 dose 0.5μg elicited anxiolytic action, whereas this action is faded away when the dose was increased. For further testing therefore 0.5μg i.c.v. was used. Propranolol and atropine fully blocked the NmU-induced anxiolytic action, while haloperidol, phenoxybenzamine and nitro-l-arginine were ineffective. The results suggest that β-adrenergic and cholinergic mechanisms are involved in the anxiolytic action of NmU. PMID:23892031

  1. Infants Recognize Similar Goals across Dissimilar Actions Involving Object Manipulation

    ERIC Educational Resources Information Center

    Olofson, Eric L.; Baldwin, Dare

    2011-01-01

    We investigated infants' ability to recognize the similarity between observed and implied goals when actions differed in surface-level motion details. In two experiments, 10- to 12-month-olds were habituated to an actor manipulating an object and then shown test actions in which the actor contacted the object with a novel hand configuration that…

  2. Humanitarian action and military intervention: temptations and possibilities.

    PubMed

    Weissman, Fabrice

    2004-06-01

    Although the war in Liberia in July 2003 claimed hundreds of lives, the international community was reluctant to intervene. In this article, the author debates the question: does international military intervention equal protection of populations? The role of humanitarian organisations in military intervention is considered. Aid organisations cannot call for deployment of a protection force without renouncing their autonomy or appealing to references outside their own practices. Such organisations provide victims with vital assistance and contribute to ensuring that their fate becomes a stake in political debate by exposing the violence that engulfs them, without substituting their own voices for those of the victims. The political content of humanitarian action is also outlined and military intervention in the context of genocide is discussed. The author concludes that the latter is one of the rare situations in which humanitarian actors can consider calling for an armed intervention without renouncing their own logic. PMID:15186365

  3. Melatonin in humans: Possible involvement in SIDS, and use in contraceptives

    NASA Technical Reports Server (NTRS)

    Wurtman, Richard J.; Lynch, Harry J.; Sturner, William Q.

    1991-01-01

    Relatively few tools exist for assessing the possible involvement of melatonin in normal or abnormal physiologlcal and behavioral states. One cannot perform the classic ablation experiment of endocrinologists by cavalierly removing the human's pineal, nor derive the same effect pharmacologically by administering a drug which blocks the actions of the indole on its receptors (because no such drugs, demonstrated to work in humans, exist). About all that can be done is to administer the melatonin and see what happens, or measure its levels in a body fluid and determine whether its temporal patterns track those of the physiological or behavioral variable being examined. The clinical state of Sudden Infant Death Syndrome (SIDS) which apparently is associated with abnormalities in melatonin concentrations within body fluids obtained at autopsy is described. New data which suggest that exogenous melatonin has sufficient antigonadal potency to allow it to replace estrogen and, acting in combination with norethisterone, serve as a useful contraceptive agent is summarized.

  4. [Receptors involved in the mechanism of action of topical prostaglandines].

    PubMed

    Neacsu, Alina Mihaela

    2009-01-01

    Hypotensive effect to prostaglandins analogs (latanoprost, travoprost, tafluprost) means to increase uveoscleral outflow by action to FP receptors who generated extracellular matrix changes and intermuscular spaces changes. Syntetic prostamides analogs (bimatoprost) have a particulary action with a receptors most and intensive studied. The bimatoprost effect is the consequences to preferated stimulations on the specific receptors who have action only the tissue with prostaglandins activity is important to specify what the bimatoprost have dual effect: to uveoscleral outflow and classic outflow by increase hidraulic conductivity. PMID:19697832

  5. Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors

    PubMed Central

    Mathes, Alexander M

    2010-01-01

    Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin’s influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy. PMID:21182223

  6. 45 CFR 73.735-903 - Action if conflicts of interest or possible conflicts are noted.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Action if conflicts of interest or possible... GENERAL ADMINISTRATION STANDARDS OF CONDUCT Reporting Financial Interests § 73.735-903 Action if conflicts of interest or possible conflicts are noted. (a) If after reviewing a financial disclosure report...

  7. 45 CFR 73.735-903 - Action if conflicts of interest or possible conflicts are noted.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Action if conflicts of interest or possible conflicts are noted. 73.735-903 Section 73.735-903 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION STANDARDS OF CONDUCT Reporting Financial Interests § 73.735-903 Action if conflicts of interest or possible conflicts are...

  8. Possible involvement of a tetrahydrobiopterin in photoreception for UV-B-induced anthocyanin synthesis in carrot.

    PubMed

    Takeda, Junko; Nakata, Rieko; Ueno, Hiroshi; Murakami, Akio; Iseki, Mineo; Watanabe, Masakatsu

    2014-01-01

    Our previous studies of action spectra for UV-B-induced anthocyanin accumulation in cultured carrot cells indicated that a reduced form of pterin, possibly tetrahydrobiopterin, contributes to UV-B photoreception. In this report, we provide additional evidence for the involvement of pterin in UV-B light sensing. UV-B-induced phenylalanine ammonia-lyase (PAL) activity was considerably suppressed by N-acetylserotonin (an inhibitor of tetrahydrobiopterin biosynthesis), and this suppression was partially recovered by adding biopterin or tetrahydrobiobiopterin. In addition, protein(s) specifically bound to biopterin were detected by radiolabeling experiments in N-acetylserotonin-treated cells. Furthermore, diphenyleneiodonium, a potent inhibitor of electron transfer, completely suppressed UV-B-induced PAL activity. These results suggest the occurrence of an unidentified UV-B photoreceptor (other than UVR8, the tryptophan-based UV-B sensor originally identified in Arabidopsis) with reduced pterin in carrot cells. After reexamining published action spectra, we suggest that anthocyanin synthesis is coordinately regulated by these two UV-B sensors. PMID:24943195

  9. Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pterostilbene, a natural analog of resveratrol, has diverse health-beneficial properties. However, the neurological activities of this compound are largely unexplored. Here we report that pterostilbene shows anxiolytic action by downregulating phosphorylated levels of ERKs in the hippocampus of mice...

  10. Current Issues Involving Affirmative Action and Higher Education

    ERIC Educational Resources Information Center

    Sterrett, William M.

    2005-01-01

    This article examines current issues regarding affirmative action in today's institutions of higher learning. It addresses the two recent cases decided before the U.S. Supreme Court concerning the University of Michigan's policy. Two other recent and related issues, the "Hopwood" case and California's Proposition 209 approach, are also examined.…

  11. Reduce Toxic Exposures: Get Involved and Take Action!

    ERIC Educational Resources Information Center

    Exceptional Parent, 2006

    2006-01-01

    There is a growing concern about the connection between many chemical exposures and learning and other developmental disabilities (LDD). National and local groups are developing new programs around the country that are making this connection--and taking action with regard to policy, education and research efforts. They are working towards reducing…

  12. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    PubMed

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases. PMID:26497928

  13. Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action.

    PubMed Central

    Nelson, R D; Shibata, N; Podzorski, R P; Herron, M J

    1991-01-01

    The ability of Candida albicans to establish an infection involves multiple components of this fungal pathogen, but its ability to persist in host tissue may involve primarily the immunosuppressive property of a major cell wall glycoprotein, mannan. Mannan and oligosaccharide fragments of mannan are potent inhibitors of cell-mediated immunity and appear to reproduce the immune deficit of patients with the mucocutaneous form of candidiasis. However, neither the exact structures of these inhibitory species nor their mechanisms of action have yet been clearly defined. Different investigators have proposed that mannan or mannan catabolites act upon monocytes or suppressor T lymphocytes, but research from unrelated areas has provided still other possibilities for consideration. These include interference with cytokine activities, lymphocyte-monocyte interactions, and leukocyte homing. To stimulate further research of the immunosuppressive property of C. albicans mannan, we have reviewed (i) the relationship of mannan to other antigens and virulence factors of the fungus; (ii) the chemistry of mannan, together with methods for preparation of mannan and mannan fragments; and (iii) the historical evidence for immunosuppression by Candida mannan and the mechanisms currently proposed for this property; and (iv) we have speculated upon still other mechanisms by which mannan might influence host defense functions. It is possible that understanding the immunosuppressive effects of mannan will provide clues to novel therapies for candidiasis that will enhance the efficacy of both available and future anti-Candida agents. PMID:2004345

  14. 17 CFR 1.67 - Notification of final disciplinary action involving financial harm to a customer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... disciplinary action involving financial harm to a customer. 1.67 Section 1.67 Commodity and Securities... Miscellaneous § 1.67 Notification of final disciplinary action involving financial harm to a customer. (a... transaction for a customer, whether executed or not, and that resulted in financial harm to the customer:...

  15. Possible action mechanism of the electromagnetic fields in the liver cancer development: A mathematical proposal

    NASA Astrophysics Data System (ADS)

    Jiménez-García, Mónica Noemí; Godina-Nava, Juan José

    2012-02-01

    Currently it is known that electromagnetic field exposure can induce biological changes, although the precise effects and action mechanism of the interaction between the electromagnetic field and biological systems are not well understood. In this work we propose a possible action mechanism, concerning the effect that the extremely low frequency electromagnetic field exposure has on the early stage of liver cancer development. The model is developed studying the phenomena called oxidative stress that it appears after it is applied a carcinogenic agent used to induce hepatic cancer chemically in an experimental animal model. This physical-chemical process involves the movement of magnetic field dependent free charged particles, called free radicals. We will consider the use of the radical pairs theory as a framework, in which we will describe the spin density operator evolution by implementing the stochastic Liouville equation with hyperfine interaction. This describes how the selectivity of the interaction between spin states of the free radicals with the applied electromagnetic field, influences the development of pre-neoplastic lesions in the liver. AIP Publishing is retracting this article due to the substantial use of content in the Results and Conclusions section without proper citation of a previously published paper in Chemical Physics Letters 361 (2012) 219-225. This article is retracted from the scientific record with effect from 15 October 2015.

  16. Involving deprived communities in improving the quality of primary care services: does participatory action research work?

    PubMed Central

    Cawston, Peter G; Mercer, Stewart W; Barbour, Rosaline S

    2007-01-01

    Background Participation by communities in improving the quality of health services has become a feature of government policy in the United Kingdom. The aim of the study was to involve a deprived community in the UK in shaping quality improvements of local primary care services. The specific objectives were firstly to create participation by local people in evaluating the primary care services available in the area and secondly to bring about change as a result of this process. Methods The methods of participatory action research was used. The study was set in an area of high socio-economic deprivation served by a 'Local Health Care Co-operative' in a peripheral housing estate in Glasgow, Scotland. 72 local residents took part in 11 focus groups: eight of these were with community groups and three with other residents. 372 local residents completed questionnaires either by brief face-to-face interviews (114) or by self or carer completion (258). Results The study group produced recommendations on physical access to the health centre, time constraints in accessing services and problems encountered in individual relationships with health staff. They also highlighted the social gap between health service providers and the daily life of community residents. Action was taken to bring these recommendations to the attention of the Primary Care Organisation. Conclusion Participatory action research was used to involve a deprived community in the UK in a 'bottom-up' approach aimed at improving quality of local primary care services. Although successful in creating a partnership between academic researchers and lay researchers and participation by local people in evaluating the primary care services available in the area, the impact of the study in terms of immediate action taken over specific issues has been modest. The possible reasons for this are discussed. PMID:17572913

  17. Possible involvement of soluble B7-H4 in T cell-mediated inflammatory immune responses.

    PubMed

    Kamimura, Yosuke; Kobori, Hiroko; Piao, Jinhua; Hashiguchi, Masaaki; Matsumoto, Koichiro; Hirose, Sachiko; Azuma, Miyuki

    2009-11-13

    B7-H4, a newly identified B7 family molecule, is reported to regulate T cell activation. However, the expression and function of B7-H4 remain controversial. Here, we demonstrated that B7-H4 expression in immune cells was undetectable at both the transcription and cell-surface protein levels. B7-H4 transfectants augmented anti-CD3 mAb-induced re-directed cytotoxicity and this was inhibited by anti-B7-H4 mAb. In a hapten-induced contact hypersensitivity model, treatment with anti-B7-H4 mAb at sensitization, but not at challenge, efficiently suppressed the ear swelling and CD8(+) T cell activation assessed by CD25 expression and IFN-gamma production. We found that cells expressing B7-H4 secreted soluble B7-H4 and the serum B7-H4 level increased with disease progression in lupus-prone and collagen-induced arthritis autoimmune mice and after the antigen challenge in allergic inflammatory diseases. Our results suggest a different action of B7-H4 in T cell-mediated inflammatory responses and the possible involvement of soluble B7-H4 in inflammatory immune responses. PMID:19723502

  18. Antithrombotic actions of statins involve PECAM-1 signaling.

    PubMed

    Moraes, Leonardo A; Vaiyapuri, Sakthivel; Sasikumar, Parvathy; Ali, Marfoua S; Kriek, Neline; Sage, Tanya; Gibbins, Jonathan M

    2013-10-31

    Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment of coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Because several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signaling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1(-/-) platelets. Activation of PECAM-1 signaling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3K), and diminished PI3K signaling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provide evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs. PMID:24030383

  19. Antithrombotic actions of statins involve PECAM-1 signaling

    PubMed Central

    Vaiyapuri, Sakthivel; Sasikumar, Parvathy; Ali, Marfoua S.; Kriek, Neline; Sage, Tanya; Gibbins, Jonathan M.

    2013-01-01

    Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment of coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Because several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signaling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1−/− platelets. Activation of PECAM-1 signaling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3K), and diminished PI3K signaling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provide evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs. PMID:24030383

  20. Factors that affect action possibility judgments: the assumed abilities of other people.

    PubMed

    Welsh, Timothy N; Wong, Lokman; Chandrasekharan, Sanjay

    2013-06-01

    Judging what actions are possible and impossible to complete is a skill that is critical for planning and executing movements in both individual and joint actions contexts. The present experiments explored the ability to adapt action possibility judgments to the assumed characteristics of another person. Participants watched alternating pictures of a person's hand moving at different speeds between targets of different indexes of difficulty (according to Fitts' Law) and judged whether or not it was possible for individuals with different characteristics to maintain movement accuracy at the presented speed. Across four studies, the person in the pictures and the background information about the person were manipulated to determine how and under what conditions participants adapted their judgments. Results revealed that participants adjusted their possibility judgments to the assumed motor capabilities of the individual they were judging. However, these adjustments only occurred when participants were instructed to take the other person into consideration suggesting that the adaption process is a voluntary process. Further, it was observed that the slopes of the regression equations relating movement time and index of difficulty did not differ across conditions. All differences between conditions were in the y-intercept of the regression lines. This pattern of findings suggests that participants formed the action possibility judgments by first simulating their own performance, and then adjusted the "possibility" threshold by adding or subtracting a correction factor to determine what is and is not possible for the other person to perform. PMID:23644579

  1. A School Action Plan with Stakeholder Involvement: A Case Study of One Elementary School

    ERIC Educational Resources Information Center

    Getty, Jacob J., Jr.

    2011-01-01

    This case study focused on a school action plan, using a planning and implementation process that focused on improving stakeholder involvement and responsibility for student reading achievement at Eisenberg Elementary School. This study examined the impact of the school action process on the development of a new plan compared to other traditional…

  2. 25 CFR 169.21 - Condemnation actions involving individually owned lands.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... 169.21 Section 169.21 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER RIGHTS-OF-WAY OVER INDIAN LANDS § 169.21 Condemnation actions involving individually owned lands. The facts relating to any condemnation action to obtain a right-of-way over individually owned lands...

  3. 25 CFR 169.21 - Condemnation actions involving individually owned lands.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... 169.21 Section 169.21 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER RIGHTS-OF-WAY OVER INDIAN LANDS § 169.21 Condemnation actions involving individually owned lands. The facts relating to any condemnation action to obtain a right-of-way over individually owned lands...

  4. 25 CFR 169.21 - Condemnation actions involving individually owned lands.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... 169.21 Section 169.21 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER RIGHTS-OF-WAY OVER INDIAN LANDS § 169.21 Condemnation actions involving individually owned lands. The facts relating to any condemnation action to obtain a right-of-way over individually owned lands...

  5. 25 CFR 169.21 - Condemnation actions involving individually owned lands.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... 169.21 Section 169.21 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER RIGHTS-OF-WAY OVER INDIAN LANDS § 169.21 Condemnation actions involving individually owned lands. The facts relating to any condemnation action to obtain a right-of-way over individually owned lands...

  6. 25 CFR 169.21 - Condemnation actions involving individually owned lands.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... 169.21 Section 169.21 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER RIGHTS-OF-WAY OVER INDIAN LANDS § 169.21 Condemnation actions involving individually owned lands. The facts relating to any condemnation action to obtain a right-of-way over individually owned lands...

  7. Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.)

    PubMed Central

    Duke, Stephen O.; Kenyon, William H.

    1986-01-01

    The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O2 evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I50 of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber. Images Fig. 2 PMID:16664919

  8. Possible Mechanism of Action of the Electromagnetic Fields of Ultralow Frequency on G-protein

    SciTech Connect

    Nava, J. J. Godina; Segura, M. A. Rodriguez; Garcia, M. N. Jimenez; Cadena, M. S. Reyes

    2008-08-11

    Based in several clinical achievements and mathematical simulation of the immune sytem, previously studied, permit us to establish that a possible Mechanism of Action of ultralow frequency Electromagnetic Fields (ELF) is on G-protein as it has been proposed in specialized literature.

  9. 45 CFR 73.735-903 - Action if conflicts of interest or possible conflicts are noted.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Action if conflicts of interest or possible conflicts are noted. 73.735-903 Section 73.735-903 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES... and the time by which it must be submitted. (b) If the reviewing official is of the opinion that,...

  10. 45 CFR 73.735-903 - Action if conflicts of interest or possible conflicts are noted.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Action if conflicts of interest or possible conflicts are noted. 73.735-903 Section 73.735-903 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES... and the time by which it must be submitted. (b) If the reviewing official is of the opinion that,...

  11. 45 CFR 73.735-903 - Action if conflicts of interest or possible conflicts are noted.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Action if conflicts of interest or possible conflicts are noted. 73.735-903 Section 73.735-903 Public Welfare Department of Health and Human Services... and the time by which it must be submitted. (b) If the reviewing official is of the opinion that,...

  12. Curriculum Theorizing and the Possibilities and Conditions for Social Action Toward Democratic Community and Education.

    ERIC Educational Resources Information Center

    Littleford, Michael S.

    1982-01-01

    An application of cultural psychoanalysis to the present culture, society, and its history examines insights into the conditions and possibilities for social action toward a higher form of democratic community. Such a community can work together in turning education toward the fulfillment of democracy. (CJ)

  13. Promise and Possibility for Aspiring Principals: An Emerging Leadership Identity through Learning to Do Action Research

    ERIC Educational Resources Information Center

    Batagiannis, Stella C.

    2011-01-01

    This case study explored the promise and possibility of doing action research both for aspiring principals engaged in such research and for professors using it as pedagogy for teaching educational leadership. The study of a class of graduate students aspiring to be principals had a constructivist theoretical framework. The research design…

  14. When does action comprehension need motor involvement? Evidence from upper limb aplasia.

    PubMed

    Vannuscorps, Gilles; Andres, Michael; Pillon, Agnesa

    2013-01-01

    Motor theories of action comprehension claim that comprehending the meaning of an action performed by a conspecific relies on the perceiver's own motor representation of the same action. According to this view, whether an action belongs to the motor repertoire of the perceiver should impact the ease by which this action is comprehended. We tested this prediction by assessing the ability of an individual (D.C.) born without upper limbs to comprehend actions involving hands (e.g., throwing) or other body parts (e.g., jumping). The tests used a range of different visual stimuli differing in the kind of information provided. The results showed that D.C. was as accurate and fast as control participants in comprehending natural video and photographic presentations of both manual and nonmanual actions, as well as pantomimes. However, he was selectively impaired at identifying point-light animations of manual actions. This impairment was not due to a difficulty in processing kinematic information per se. D.C. was indeed as accurate as control participants in two additional tests requiring a fine-grained analysis of an actor's arm or whole-body movements. These results challenge motor theories of action comprehension by showing that the visual analysis of body shape and motion provides sufficient input for comprehending observed actions. However, when body shape information is sparsely available, motor involvement becomes critical to interpret observed actions. We suggest that, with natural human movement stimuli, motor representations contribute to action comprehension each time visual information is incomplete or ambiguous. PMID:24215324

  15. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  16. Mediators involved in the hyperthermic action of neuromedin U in rats.

    PubMed

    Telegdy, G; Adamik, A

    2014-01-01

    Neuromedin U (NmU), first was isolated from the porcine spinal cord, has subsequently been demonstrated in a number of species, in which it is present in the periphery and also the brain. Two receptors have been identified: NmU1R is mainly present in peripheral tissues, and Nmu2R in the central nervous system. NmU, a potent endogenous anorectic, serves as a catabolic signaling molecule in the brain; it inhibits food uptake, increases locomotion, activates stress mechanism, having cardiovasscular effects and, causes hyperthermia. The mechanism of this hyperthermia is unknown. In the present experiments, the effects of NmU on the colon temperature following i.c.v administration were studied in rats. For an investigation of the possible role of receptors in mediating hyperthermia, the animals were treated simultaneously with CRF 9-41 and antalarmin, a CRH1 receptor inhibitors, astressin 2B, a CRH2 receptor antagonist, haloperidol a dopamine receptor antagonist, atropine a muscarinic cholinergic receptor antagonist, noraminophenazone a cyclooxygenase inhibitor or isatin, a prostaglandin receptor antagonist. NmU increased the colon temperature, maximal action being observed at 2-3h. CRF 9-41, antalarmin, astressin 2B haloperidol, atropine, noraminophenazone and isatin prevented the NmU-induced increase in colon temperature. The results demonstrated that, when injected into the lateral brain ventricle NmU increased the body temperature, mediated by CRHR1 and CRHR2, dopamine and muscarinic cholinergic receptors. The final pathway involves prostaglandin. PMID:25108055

  17. Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine.

    PubMed

    Caillier, Bertrand; Pilote, Sylvie; Patoine, Dany; Levac, Xavier; Couture, Christian; Daleau, Pascal; Simard, Chantale; Drolet, Benoit

    2012-03-01

    Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals. Male Hartley guinea pigs were fed with either the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides, urea and glucose tolerance were regularly monitored. Histopathological evolution was also evaluated in target organs such as pancreas, heart, liver and kidneys. Ex vivo experiments using the Langendorff retroperfusion technique, isolated hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet were exposed to dofetilide 20 nM (D), chromanol 293B 10 μM (C) and amlodipine 100 nM (A) in different drug combinations and monophasic action potential duration was measured at 90% repolarization (MAPD₉₀). Our data show that it is possible to generate a guinea pig model of metabolic syndrome by chronic exposure to diabetogenic diets. Minor histopathological abnormalities were observed, mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD-prolonging actions of I(Kr)-blocking (dofetilide) and I(Ks)-blocking (chromanol 293B) drugs, an effect that is reversible upon administration of the calcium channel blocker amlodipine. PMID:22154802

  18. Antidepressant-like action of the hydromethanolic flower extract of Tagetes erecta L. in mice and its possible mechanism of action

    PubMed Central

    Khulbe, Aarti; Pandey, Savita; Sah, Sangeeta Pilkhwal

    2013-01-01

    Objective: Tagetes erecta, the marigold, has commercial and ethnomedicinal use; however, reports concerning its efficacy for the treatment of depression are lacking. This study was carried out to elucidate the antidepressant effect of hydromethanolic flower extract of T. erecta. Materials and Methods: Hydromethanolic extract of flowers of Tagetes erecta was subjected to preliminary phytochemical screening. The extract (12.5, 25, and 50 mg/kg, i.p.) was evaluated for antidepressant effect using forced swim test in mice. The mechanism of antidepressant action was further examined using different drugs and imipramine was used as standard drug. Results: T. erecta significantly inhibited the immobility period in forced swim test in mice P<0.05). T. erecta (25 mg/kg, i.p.) enhanced the anti-immobility effect of antidepressant drugs like imipramine, fluoxetine, and p-chlorophenylalanine, an inhibitor of serotonin synthesis significantly attenuated its antidepressant effect. The antidepressant effect of T. erecta in the forced swim test was prevented by pretreatment with L-arginine and sildenafil, whereas pretreatment of mice with nitric oxide synthase inhibitors potentiated the action. Pentazocine, a high-affinity sigma receptor agonist, produced synergism with effective dose of T. erecta while progesterone, a sigma receptor antagonist, reversed the antidepressant effect of T. erecta. However, the locomotor activity was not affected at tested doses. Conclusions: Serotonergic, nitrergic pathway, and sigma receptors are possibly involved in mediating antidepressant action of T. erecta in mouse forced swim test. PMID:24014916

  19. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools

    PubMed Central

    Frey, Scott H.; Povinelli, Daniel J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use. PMID:22106426

  20. Additional Evidence of the Trypanocidal Action of (−)-Elatol on Amastigote Forms through the Involvement of Reactive Oxygen Species

    PubMed Central

    Desoti, Vânia Cristina; Lazarin-Bidóia, Danielle; Sudatti, Daniela Bueno; Pereira, Renato Crespo; Ueda-Nakamura, Tania; Nakamura, Celso Vataru; de Oliveira Silva, Sueli

    2014-01-01

    Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action of (−)-elatol, extracted from the macroalga Laurencia dendroidea. However, nothing has been described about the mechanism of action of this compound on amastigotes that are involved in the chronic phase of Chagas’ disease. The goal of the present study was to evaluate the effect of (−)-elatol on the formation of superoxide anions (O2•−), DNA fragmentation, and autophagy in amastigotes of T. cruzi to elucidate the possible mechanism of the trypanocidal action of (−)-elatol. Treatment of the amastigotes with (−)-elatol increased the formation of O2•− at all concentrations of (−)-elatol assayed compared with untreated parasites. Increased fluorescence was observed in parasites treated with (−)-elatol, indicating DNA fragmentation and the formation of autophagic compartments. The results suggest that the trypanocidal action of (−)-elatol might involve the induction of the autophagic and apoptotic death pathways triggered by an imbalance of the parasite’s redox metabolism. PMID:25257785

  1. Imitation and observational learning of hand actions: prefrontal involvement and connectivity.

    PubMed

    Higuchi, S; Holle, H; Roberts, N; Eickhoff, S B; Vogt, S

    2012-01-16

    The first aim of this event-related fMRI study was to identify the neural circuits involved in imitation learning. We used a rapid imitation task where participants directly imitated pictures of guitar chords. The results provide clear evidence for the involvement of dorsolateral prefrontal cortex, as well as the fronto-parietal mirror circuit (FPMC) during action imitation when the requirements for working memory are low. Connectivity analyses further indicated a robust connectivity between left prefrontal cortex and the components of the FPMC bilaterally. We conclude that a mechanism of automatic perception-action matching alone is insufficient to account for imitation learning. Rather, the motor representation of an observed, complex action, as provided by the FPMC, only serves as the 'raw material' for higher-order supervisory and monitoring operations associated with the prefrontal cortex. The second aim of this study was to assess whether these neural circuits are also recruited during observational practice (OP, without motor execution), or only during physical practice (PP). Whereas prefrontal cortex was not consistently activated in action observation across all participants, prefrontal activation intensities did predict the behavioural practice effects, thus indicating a crucial role of prefrontal cortex also in OP. In addition, whilst OP and PP produced similar activation intensities in the FPMC when assessed during action observation, during imitative execution, the practice-related activation decreases were significantly more pronounced for PP than for OP. This dissociation indicates a lack of execution-related resources in observationally practised actions. More specifically, we found neural efficiency effects in the right motor cingulate-basal ganglia circuit and the FPMC that were only observed after PP but not after OP. Finally, we confirmed that practice generally induced activation decreases in the FPMC during both action observation and

  2. Motor control hierarchy in joint action that involves bimanual force production

    PubMed Central

    Masumoto, Junya

    2015-01-01

    The concept of hierarchical motor control has been viewed as a means of progressively decreasing the number of variables manipulated by each higher control level. We tested the hypothesis that turning an individual bimanual force-production task into a joint (two-participant) force-production task would lead to positive correlation between forces produced by the two hands of the individual participant (symmetric strategy) to enable negative correlation between forces produced by two participants (complementary strategy). The present study consisted of individual and joint tasks that involved both unimanual and bimanual conditions. In the joint task, 10 pairs of participants produced periodic isometric forces, such that the sum of forces that they produced matched a target force cycling between 5% and 10% of maximum voluntary contraction at 1 Hz. In the individual task, individuals attempted to match the same target force. In the joint bimanual condition, the two hands of each participant adopted a symmetric strategy of force, whereas the two participants adopted a complementary strategy of force, highlighting that the bimanual action behaved as a low level of a hierarchy, whereas the joint action behaved as an upper level. The complementary force production was greater interpersonally than intrapersonally. However, whereas the coherence was highest at 1 Hz in all conditions, the frequency synchrony was stronger intrapersonally than interpersonally. Moreover, whereas the bimanual action exhibited a smaller error and variability of force than the unimanual action, the joint action exhibited a less-variable interval and force than the individual action. PMID:25904710

  3. The involvement of the left motor cortex in learning of a novel action word lexicon.

    PubMed

    Liuzzi, Gianpiero; Freundlieb, Nils; Ridder, Volker; Hoppe, Julia; Heise, Kirstin; Zimerman, Maximo; Dobel, Christian; Enriquez-Geppert, Stefanie; Gerloff, Christian; Zwitserlood, Pienie; Hummel, Friedhelm C

    2010-10-12

    Current theoretical positions assume that action-related word meanings are established by functional connections between perisylvian language areas and the motor cortex (MC) according to Hebb's associative learning principle. To test this assumption, we probed the functional relevance of the left MC for learning of a novel action word vocabulary by disturbing neural plasticity in the MC with transcranial direct current stimulation (tDCS). In combination with tDCS, subjects learned a novel vocabulary of 76 concrete, body-related actions by means of an associative learning paradigm. Compared with a control condition with "sham" stimulation, cathodal tDCS reduced success rates in vocabulary acquisition, as shown by tests of novel action word translation into the native language. The analysis of learning behavior revealed a specific effect of cathodal tDCS on the ability to associatively couple actions with novel words. In contrast, we did not find these effects in control experiments, when tDCS was applied to the prefrontal cortex or when subjects learned object-related words. The present study lends direct evidence to the proposition that the left MC is causally involved in the acquisition of novel action-related words. PMID:20888226

  4. Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain.

    PubMed

    Tomohisa, Mori; Junpei, Ohya; Aki, Masumoto; Masato, Harumiya; Mika, Fukase; Kazumi, Yoshizawa; Teruo, Hayashi; Tsutomu, Suzuki

    2015-11-01

    Previous studies have shown that ligands of the sigma-1 receptor chaperone (Sig-1R) regulate pain-related behaviors. Clinical use of chemotherapeutics is often compromised due to their adverse side effects, particularly those related to neuropathy. Previous studies have shown that repeated administration of oxaliplatin and paclitaxel produces neuropathy in rodents. Therefore, the aim of the present study was to clarify the involvement of the Sig-1R in chemotherapeutic-induced neuropathy by examining the effects of oxaliplatin and paclitaxel on the Sig-1R levels in the spinal cord, and by examining the effects of Sig-1R agonist and antagonist on oxaliplatin- and paclitaxel-induced neuropathy in rats. Chemotherapeutic-induced neuropathic pain was accompanied by a significant reduction of the Sig-1R level in the spinal cord. Furthermore, the administration of paclitaxel to CHO cells that stably overexpressed Sig-1Rs induced the clustering of Sig-1Rs. We also found that the Sig-1R agonist SA4503 potently inhibited the neuropathy induced by oxaliplatin- and paclitaxel, whereas this action was abolished by the Sig-1R antagonist NE-100. These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy. PMID:26234785

  5. Location of several putative genes possibly involved in human breast cancer progression.

    PubMed

    Driouch, K; Briffod, M; Bièche, I; Champème, M H; Lidereau, R

    1998-05-15

    Cancer is a genetic disease resulting from an accumulation of genetic abnormalities in various regulatory genes. Most studies on genetic alterations in human breast cancer have involved primary tumors. The possible involvement of specific tumor suppressor genes in the later stages of cancer progression is poorly documented. We investigated allelic losses associated with breast cancer progression by analyzing 55 polymorphic markers on 11 autosomal chromosomes in a series of 49 relapses (23 local recurrences and 26 distant metastases). All of the loss of heterozygosity (LOH) regions reported in primary breast tumors were frequent in both series of relapses. These results suggest that the allelic losses that are common to the different series of samples occur very early during tumor progression. This study points to candidate metastasis-related genes targeted by LOH on chromosome arms 3p21.3, 16q22.2-23.2, and, possibly, 7q31 but provides no clear evidence of LOH affecting previously described metastasis-related genes such as NME1, MTS1, and TSG101. PMID:9605747

  6. Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System of Female Olive Flounder Paralichthys olivaceus

    PubMed Central

    Kim, Hyun Chul; Lee, Chi Hoon; Hur, Sung Pyu; Kim, Byeong Hoon; Park, Jun Young; Lee, Young Don

    2015-01-01

    This study investigated possible involvement of photoperiodic regulation in reproductive endocrine system of female olive flounder. To investigate the influence on brain-pituitary axis in endocrine system by regulating photoperiod, compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-β, LH-β and GH mRNA in pituitary before and after spawning. Photoperiod was treated natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase) was inhibited gonadal development of female olive flounder. In natural photoperiod group, the Kiss2 expression level a significant declined in Mar. (spawning period). And also, FSH-β, LH-β and GH mRNA expression levels were increasing at this period. However, in long photoperiod group, hypothalamic Kiss2, FSH-β, LH-β and GH mRNA expression levels did not show any significant fluctuation. These results suggest that expression of hypothalamic Kiss2, GtH and GH in the pituitary would change in response to photoperiod and their possible involvement of photoperiodic regulation in reproductive endocrine system of the BPG axis. PMID:25949205

  7. Sparteine as an anticonvulsant drug: Evidence and possible mechanism of action.

    PubMed

    Villalpando-Vargas, Fridha; Medina-Ceja, Laura

    2016-07-01

    Sparteine is a quinolizidine alkaloid extracted from Lupinus that has numerous pharmacological properties both in humans and animal models. In the central nervous system, sparteine reduces locomotor activity, has light analgesic effects, also has no effects on short-term memory or spatial learning and does not induce changes in behavior or electroencephalographic (EEG) activity. However, the anticonvulsant profile of sparteine is not fully characterized in experimental animals and there are no data in humans. Therefore, the present review focuses on the experimental evidence supporting the anticonvulsant action of sparteine in models of acute seizures and status epilepticus (SE), as well as its possible mechanisms of action. The evidence that supports the anticonvulsant effect of (-)-Sparteine sulfate includes the inhibition of seizures induced by maximal electro-stimulation, a delay in the onset of convulsive behavior and the prolongation of survival time in mice treated with pentylenetetrazole (PTZ). Additionally, sparteine delays the onset of convulsive behavior and decreases the severity and mortality of rats treated with PTZ and pilocarpine. Sparteine decreases amplitude and frequency or blocks the epileptiform activity induced by PTZ, pilocarpine and kainic acid. Sparteine may decrease hyperexcitability through the activation of the M2 and M4 subtypes of mAChRs, which is a probable mechanism of action that together with its systemic effects may favor its anticonvulsant effects against seizures and SE. PMID:27262285

  8. Glucagon actions on the kidney revisited: possible role in potassium homeostasis.

    PubMed

    Bankir, Lise; Bouby, Nadine; Blondeau, Bertrand; Crambert, Gilles

    2016-08-01

    It is now recognized that the metabolic disorders observed in diabetes are not, or not only due to the lack of insulin or insulin resistance, but also to elevated glucagon secretion. Accordingly, selective glucagon receptor antagonists are now proposed as a novel strategy for the treatment of diabetes. However, besides its metabolic actions, glucagon also influences kidney function. The glucagon receptor is expressed in the thick ascending limb, distal tubule, and collecting duct, and glucagon regulates the transepithelial transport of several solutes in these nephron segments. Moreover, it also influences solute transport in the proximal tubule, possibly by an indirect mechanism. This review summarizes the knowledge accumulated over the last 30 years about the influence of glucagon on the renal handling of electrolytes and urea. It also describes a possible novel role of glucagon in the short-term regulation of potassium homeostasis. Several original findings suggest that pancreatic α-cells may express a "potassium sensor" sensitive to changes in plasma K concentration and could respond by adapting glucagon secretion that, in turn, would regulate urinary K excretion. By their combined actions, glucagon and insulin, working in a combinatory mode, could ensure an independent regulation of both plasma glucose and plasma K concentrations. The results and hypotheses reviewed here suggest that the use of glucagon receptor antagonists for the treatment of diabetes should take into account their potential consequences on electrolyte handling by the kidney. PMID:27194722

  9. Possible involvement of eEF1A in Tomato spotted wilt virus RNA synthesis.

    PubMed

    Komoda, Keisuke; Ishibashi, Kazuhiro; Kawamura-Nagaya, Kazue; Ishikawa, Masayuki

    2014-11-01

    Tomato spotted wilt virus (TSWV) is a negative-strand RNA virus in the family Bunyaviridae and propagates in both insects and plants. Although TSWV can infect a wide range of plant species, host factors involved in viral RNA synthesis of TSWV in plants have not been characterized. In this report, we demonstrate that the cell-free extract derived from one of the host plants can activate mRNA transcriptional activity of TSWV. Based on activity-guided fractionation of the cell-free extract, we identified eukaryotic elongation factor (eEF) 1A as a possible host factor facilitating TSWV transcription and replication. The RNA synthesis-supporting activity decreased in the presence of an eEF1A inhibitor, suggesting that eEF1A plays an important role in RNA synthesis of TSWV. PMID:25151062

  10. On the possible involvement of bovine serum albumin precursor in lipofection pathway.

    PubMed

    Mukherjee, Anubhab; Bhattacharyya, Jayanta; Chaudhuri, Arabinda

    2014-03-01

    Protein factors involved in lipofection pathways remain elusive. Using avidin-biotin affinity chromatography and mass finger printing analysis technique, herein we report the identification of a 70 kDa size protein (bovine serum albumin precursor, BSAP) which binds strongly with lipoplexes and may play role in lipofection pathway. Using multiple cultured animal cells and three structurally different cationic transfection lipids, we show that the efficiencies of liposomal transfection vectors get significantly enhanced (by ~2.5- to 5.0-fold) in cells pre-transfected with lipoplexes of reporter plasmid construct encoding BSAP. Findings in the cellular uptake experiments in A549 cells cultured in DMEM supplemented with 10 percent (w/w) BODIPY-labelled BSAP are consistent with the supposition that BSAP enters cell cytoplasm from the cell culture medium (DMEM supplemented with 10 percent FBS) used in lipofection. Cellular uptake studies by confocal microscopy using BODIPY-labelled BSAP and FITC-labelled plasmid DNA revealed co-localization of plasmid DNA and BSAP within the cell cytoplasm and nucleus. In summary, the present findings hint at the possible involvement of BSAP in lipofection pathway. PMID:24499789

  11. Possible involvement of Epstein-Barr virus in the pathogenesis of Sjogren's syndrome.

    PubMed

    Miyasaka, N; Saito, I; Haruta, J

    1994-08-01

    We examined the possible involvement of Epstein-Barr virus (EBV) in the pathogenesis of Sjogren's syndrome (SS) using B cell lines (BCLs) spontaneously established from the peripheral blood. These BCLs were positive for EBNA and produced a large amount of infecting EBV in culture, a feature unique to SS-BCLs. Polymerase chain reaction analysis revealed that EBV with a B95-8-like U2 region was dominant in SS-BCLs. The nucleotide sequences of the U2 region of SS-EBV obtained so far have shown high homology to those of B95-8 EBV. However, there was a substantial amount of deletion and substitution of nucleotides within the U2 region of SS-EBV when compared with B95-8 EBV. This might enable SS-BCLs to escape immune recognition by cytotoxic T cells specific to EBNA-2. In addition, SS-EBV contains the sequence that spans the B95-8-deleted region. Furthermore, transfer of SS-BCLs to SCID mice induced monoclonal lymphoproliferative disorders that resembled those arising in SS. These data further support the motion that reactivation of EBV is deeply involved in polyclonal B cell activation and the development of B cell malignancies in SS. PMID:8050188

  12. Estrogenic activity of procymidone in rainbow trout (Oncorhynchus mykiss) hepatocytes: a possible mechanism of action.

    PubMed

    Radice, Sonia; Fumagalli, Roberta; Chiesara, Enzo; Ferraris, Michela; Frigerio, Silvia; Marabini, Laura

    2004-03-15

    It is known that procymidone modifies sexual differentiation in vivo and in vitro, and that it induces vitellogenin (Vtg) synthesis in primary cultured rainbow trout hepatocytes. The aim of this study was to evaluate the mechanism underlying this latter in vitro estrogenic action. The cells were treated for 24 h with procymidone 150 microM (with 17beta-estradiol [E2] 20 microM as a positive control) combined with an estrogen receptor (ER) antagonist (tamoxifen 20 microM or ICI 182,780 1 microM) or, given the drug toxic action on the production of reactive oxygen species (ROS), a free radical scavenger (alpha-tocopherol 30 microM). The results from ELISA experiments provided evidence that procymidone Vtg-induction is inhibited by ER antagonists and by alpha-tocopherol suggesting that both ER and ROS are involved in this effect. The ROS detection revealed that the treatment with alpha-tocopherol and tamoxifen completely prevented ROS induction by procymidone, that was not inhibited by ICI 182,780. In exploring the mechanism mediating these events and its timing, we found that procymidone induced mitogen-activated protein kinase (MAPK) at 30 and 60 min, and that this effect was blocked by co-treatment with alpha-tocopherol. In summary, the results of the study clearly support the idea that the estrogenic activity of procymidone in primary cultured trout hepatocytes is mediated by ROS production, and that this activity is similar to that of the ligand-independent ER activation involving MAPK. PMID:15013820

  13. 31 CFR 363.45 - What are the rules for judicial and administrative actions involving securities held in...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... administrative actions involving securities held in TreasuryDirect ®? 363.45 Section 363.45 Money and Finance... Governing Securities Held in TreasuryDirect § 363.45 What are the rules for judicial and administrative actions involving securities held in TreasuryDirect ®? (a) Notice of adverse claim or pending...

  14. 31 CFR 363.45 - What are the rules for judicial and administrative actions involving securities held in...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... administrative actions involving securities held in TreasuryDirect ®? 363.45 Section 363.45 Money and Finance... Governing Securities Held in TreasuryDirect § 363.45 What are the rules for judicial and administrative actions involving securities held in TreasuryDirect ®? (a) Notice of adverse claim or pending...

  15. 31 CFR 363.45 - What are the rules for judicial and administrative actions involving securities held in...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... administrative actions involving securities held in TreasuryDirect ®? 363.45 Section 363.45 Money and Finance... Governing Securities Held in TreasuryDirect § 363.45 What are the rules for judicial and administrative actions involving securities held in TreasuryDirect ®? (a) Notice of adverse claim or pending...

  16. 31 CFR 363.45 - What are the rules for judicial and administrative actions involving securities held in...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... administrative actions involving securities held in TreasuryDirect ®? 363.45 Section 363.45 Money and Finance... Governing Securities Held in TreasuryDirect § 363.45 What are the rules for judicial and administrative actions involving securities held in TreasuryDirect ®? (a) Notice of adverse claim or pending...

  17. Is patient involvement possible when decisions involve scarce resources? A qualitative study of decision-making in primary care.

    PubMed

    Jones, Ian Rees; Berney, Lee; Kelly, Moira; Doyal, Len; Griffiths, Chris; Feder, Gene; Hillier, Sheila; Rowlands, Gillian; Curtis, Sarah

    2004-07-01

    Greater patient involvement has become a key goal of health care provision. This study explored the way in which general practitioners (GPs) in the UK manage the dual responsibilities of treating individual patients and making the most equitable use of National Health Service (NHS) resources in the context of the policy of greater patient involvement in decision-making. We undertook a qualitative study incorporating a series of interviews and focus groups with a sample of 24 GPs. We analysed GP accounts of decision-making by relating these to substantive ethical principles and the key procedural principle of explicitness in decision-making. GPs saw patient involvement in positive terms but for some GPs involvement served an instrumental purpose, for instance improving patient 'compliance'. GPs identified strongly with the role of patient advocate but experienced role tensions particularly with respect to wider responsibilities for budgets, populations, and society in general. GPs had an implicit understanding of the key ethical principle of explicitness and of other substantive ethical principles but there was incongruence between these and their interpretation in practice. Limited availability of GP time played an important role in this theory/practice gap. GPs engaged in implicit categorisation of patients, legitimating this process by reference to the diversity and complexity of general practice. If patient involvement in health care decision-making is to be increased, then questions of scarcity of resources, including time, will need to be taken into account. If strategies for greater patient involvement are to be pursued then this will have significant implications for funding primary care, particularly in terms of addressing the demands made on consultation time. Good ethics and good professional practice cost money and must be budgeted for. More explicit decision-making in primary care will need to be accompanied by greater explicitness at the national level

  18. Antinociceptive action of mitragynine in mice: evidence for the involvement of supraspinal opioid receptors.

    PubMed

    Matsumoto, K; Mizowaki, M; Suchitra, T; Takayama, H; Sakai, S; Aimi, N; Watanabe, H

    1996-01-01

    Mitragynine is a major alkaloidal constituent extracted from the young leaves of Mitragyna speciosa Korth. (Rubiaceae). We investigated an antinociceptive activity of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection of this alkaloid by the tail-pinch and hot-plate tests in mice, and evaluated the mechanisms of the action using naloxone, an opioid receptor antagonist. Mitragynine (5.0-30 mg/kg, i.p. and 1.0-10 micrograms/mouse, i.c.v.) exerted a dose-dependent antinociceptive activity which was maximal at 15-45 min after injection in the tail-pinch and hot-plate tests, but it did not induce a morphine-like behavioral change. the antinociceptive actions of i.p. mitragynine were completely abolished by both s.c. (2 mg/kg) and i.c.v (10 micrograms/mouse) naloxone. The action of i.c.v. mitragynine (10 micrograms/mouse) was also antagonized by i.c.v. naloxone (10 micrograms/mouse). These results indicate that mitragynine itself can induce antinociception by acting in the brain, and that the supraspinal opioid systems are at least partly involved in the antinociceptive action of mitragynine in mice. PMID:8831802

  19. Trypanocidal Action of (−)-Elatol Involves an Oxidative Stress Triggered by Mitochondria Dysfunction

    PubMed Central

    Desoti, Vânia Cristina; Lazarin-Bidóia, Danielle; Sudatti, Daniela Bueno; Pereira, Renato Crespo; Alonso, Antonio; Ueda-Nakamura, Tania; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; Silva, Sueli de Oliveira

    2012-01-01

    Natural compounds have shown good potential for the discovery of new chemotherapeutics for the treatment of Chagas’ disease. Recently, our group reported the effective trypanocidal activity of (−)-elatol, extracted from the red macroalgae Laurencia dendroidea present in the Brazilian coast against Trypanosoma cruzi. However, the mechanism of action of this compound has remained unclear. There are only hypotheses concerning its action on mitochondrial function. Here, we further investigated the mechanisms of action of (−)-elatol on trypomastigotes of T. cruzi. For this, we evaluated some biochemical alterations in trypomastigotes treated with (−)-elatol. Our results show that (−)-elatol induced depolarization of the mitochondrial membrane, an increase in the formation of mitochondrial superoxide anion and loss of cell membrane and DNA integrity. Additionally, (−)-elatol induced formation of autophagic vacuoles and a decrease in cell volume. All together, these results suggest that the trypanocidal action of (−)-elatol involves multiple events and mitochondria might be the initial target organelle. Our hypothesis is that the mitochondrial dysfunction leads to an increase of ROS production through the electron transport chain, which affects cell membrane and DNA integrity leading to different types of parasite death. PMID:23015766

  20. Involvement of cell wall beta-glucan in the action of HM-1 killer toxin.

    PubMed

    Kasahara, S; Ben Inoue, S; Mio, T; Yamada, T; Nakajima, T; Ichishima, E; Furuichi, Y; Yamada, H

    1994-07-01

    HM-1 killer toxin secreted from Hansenula mrakii inhibits the growth of Saccharomyces cerevisiae cells by interfering with beta-1,3-glucan synthesis. We found that HM-1 killer toxin killed intact cells but not protoplasts. In addition, cells lacking the functional KRE6 allele (kre6 delta) became resistant to higher concentration of HM-1 killer toxin. As reported by Roemer and Bussey [(1991) Proc. Natl. Acad. Sci. 88 11295-11299], cells lacking functional KRE6 had a reduced level of the cell wall beta-1,6-glucan compared to that in cells harboring the normal KRE6. These results suggest that the cell wall beta-glucan is involved in the action of HM-1 killer toxin. Addition of HM-1 killer toxin with several kinds of oligosaccharides revealed that either beta-1,3- or beta-1,6-glucan blocked the cytocidal action of HM-1 killer toxin whereas alpha-1,4-glucan and chitin did not. Mannan also interfered with HM-1 killer toxin action, but this inhibitory effect was much weaker than that observed with beta-1,3- or beta-1,6-glucans. Thus, it appears that the cell wall beta-glucan interacts with HM-1 killer toxin, and that this toxin-beta-glucan commitment is required for the action of HM-1 killer toxin. PMID:8026578

  1. Ledge and wedge: younger and older adults' perception of action possibilities

    PubMed Central

    Comalli, David; Franchak, John; Char, Angela

    2013-01-01

    The current study investigated whether younger (college-age) and older adults (60+ years) differ in their ability to perceive safe and unsafe motor actions. Participants decided whether to walk through openings varying in width in two penalty conditions: In the doorway condition, if participants attempted to squeeze through impossibly narrow openings, the penalty for error was entrapment. In the ledge condition, if participants attempted to inch along impossibly narrow ledges, the penalty for error was falling. Results showed that across the lifespan, people consider falling to be a more severe penalty than getting stuck: Both younger and older adults made more conservative decisions when the penalty for error was falling, and older women were especially leery of falling. In both age groups, abilities and decisions were based on dynamic properties of the body, such as compressed body size in the doorway condition and balance in the ledge condition. Findings indicate that failure to perceive possibilities for action is unlikely to be the cause of the increased prevalence of falling in older adults. PMID:23660744

  2. Use of active extracts of poplar buds against Penicillium italicum and possible modes of action.

    PubMed

    Yang, Shuzhen; Liu, Limei; Li, Dongmei; Xia, Huan; Su, Xiaojun; Peng, Litao; Pan, Siyi

    2016-04-01

    Antifungal components, from poplar buds active fraction (PBAF) against Penicillium italicum, the causal agent of blue mold in citrus fruits, were identified and possible action modes were investigated. Pinocembrin, chrysin and galangin were determined as active components in PBAF, using HPLC and HPLC-MS analysis. The antifungal activity is stable at temperatures ranging from 4 °C to 100 °C and pH levels ranging from 4 to 8. In the presence of PBAF, the hyphae become shriveled, wrinkled and the cell membrane became seriously disrupted. Further investigation on cell permeability, nucleic acid content and alkaline phosphatase suggest that the cell membrane might be the target. Mycelial oxygen consumption and the respiration-related enzymatic activity of succinate dehydrogenase, malate dehydrogenase and ATPase were all inhibited by PBAF. We propose that PBAF is a potentially useful alternative for blue mold control and may act against P. italicum by interfering with respiration and disrupting the cell membrane. PMID:26593534

  3. A phenomenographic analysis of first-year engineering students' experiences with problems involving multiple possible solutions

    NASA Astrophysics Data System (ADS)

    Dringenberg, Emily A.

    Engineers are expected to solve problems that are ill-structured. These problems are presented with a lack of necessary information and allow for different ways of engaging with the problem; they are open-ended and involve multiple possible solutions with multiple means of evaluation. In order to allow maximum time for students to develop skills for solving such problems, undergraduate engineering programs can introduce such problems during the first year of students' education, in the form of cornerstone design tasks. This provides students with more opportunities to develop their ability to engage with ill-structured problems, which are characteristic of engineering work. Researchers have documented variation within both the behavior and perceptions of students' early experiences with design problems. General themes include novice-like design behavior, discomfort with lack of information, difficulty with problem scoping, and resistance to ambiguity. To build on these generalizations of students' experiences, a more thorough understanding of the variation in how students experience this phenomenon of engaging with ill-structured problems is needed to design effective learning environments. This work presents the qualitatively different ways that engineering students experience problems with multiple possible solutions during their first year of engineering studies. Using phenomenography as the methodological framework, data were collected through in-depth, semi-structured interviews with 27 first-year engineering students. The iterative, phenomenographic analysis resulted in seven descriptive categories for the ways participants experienced problems involving multiple possible solutions. The names of these categories represent the different foci of the students' experiences: completion, transition, iteration, organization, collaboration, reasoning, and growth. These categories are organized along two crucial dimensions of variation: reaction to ambiguity and role

  4. Cinnamic Acid Is Partially Involved in Propolis Immunomodulatory Action on Human Monocytes

    PubMed Central

    Conti, Bruno José; Búfalo, Michelle Cristiane; Golim, Marjorie de Assis; Sforcin, José Maurício

    2013-01-01

    Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci). The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs), HLA-DR, and CD80. Cytokine production (TNF-α and IL-10) and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF-α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF-α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities. PMID:23762102

  5. Cinnamic Acid is partially involved in propolis immunomodulatory action on human monocytes.

    PubMed

    Conti, Bruno José; Búfalo, Michelle Cristiane; Golim, Marjorie de Assis; Bankova, Vassya; Sforcin, José Maurício

    2013-01-01

    Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci). The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs), HLA-DR, and CD80. Cytokine production (TNF- α and IL-10) and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF- α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF- α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities. PMID:23762102

  6. The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex.

    PubMed

    Spencer, Robert C; Devilbiss, David M; Berridge, Craig W

    2015-06-01

    Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. In contrast, while the striatum is a critical participant in PFC-dependent cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g., working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation. PMID:25499957

  7. The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex

    PubMed Central

    Spencer, Robert C.; Devilbiss, David M.; Berridge, Craig W.

    2014-01-01

    Psychostimulants are highly effective in the treatment of attention deficit hyperactivity disorder (ADHD). The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2- and dopamine D1 receptors. In contrast, while the striatum is a critical participant in ‘PFC-dependent’ cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g. working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 vs. α1 receptors. Collectively, this evidence indicates that at low, clinically-relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacological treatments for ADHD and other conditions associated with PFC dysregulation. PMID:25499957

  8. It may be possible to construct a Chemical Synthesizing Computer based on Capillary Action

    NASA Astrophysics Data System (ADS)

    Kriske, Richard

    2013-03-01

    This author had previously proposed that Capillary Action has a Quantum Mechanical Model. This model can be easily constructed by noting that when a photon of the heat wavelength evaporates one molecule of water at the top of a capillary column, a ``hole'' is transmitted from the top of the column to the roots and into the water reservoir sustaining the capillary tube. This ``hole'' is a true hole (a true particle) in that it is transmitted as a quantized unit through the capillary tube. The mathematics of this process are the same as used in Quantum Field Theory, with the capillary acting as a perfect spring (like the spring used on a ``stack'' of dishes). When the external field using a force to pull the water molecule off the stack, an equal and opposite spring force (which is quantized), is transmitted down the column to the reservoir. When the water is not pure, this author proposes that each of the elements in the unpure water act linearly, each with its own quantized spring constant that does not interact with the other quantized spring constants, so it is possible to pull a single electron off the top of the water stack, yet the water in the stack is undisturbed (the reservoir is disturbed). Likewise it is possible to pull a sugar molecule off and balance chemical equations.

  9. Dioxin risk assessment: mechanisms of action and possible toxicity in human health.

    PubMed

    Tavakoly Sany, Seyedeh Belin; Hashim, Rosli; Salleh, Aishah; Rezayi, Majid; Karlen, David J; Razavizadeh, Bi Bi Marzieh; Abouzari-Lotf, Ebrahim

    2015-12-01

    Dioxin-like compounds (DLCs) have been classified by the World Health Organization (WHO) as one of the most persistent toxic chemical substances in the environment, and they are associated with several occupational activities and industrial accidents around the world. Since the end of the 1970s, these toxic chemicals have been banned because of their human toxicity potential, long half-life, wide dispersion, and they bioaccumulate in the food web. This review serves as a primer for environmental health professionals to provide guidance on short-term risk assessment of dioxin and to identify key findings for health and exposure assessment based on policies of different agencies. It also presents possible health effects of dioxins, mechanisms of action, toxic equivalency factors (TEFs), and dose-response characterization. Key studies related to toxicity values of dioxin-like compounds and their possible human health risk were identified through PubMed and supplemented with relevant studies characterized by reviewing the reference lists in the review articles and primary literature. Existing data decreases the scope of analyses and models in relevant studies to a manageable size by focusing on the set of important studies related to the perspective of developing toxicity values of DLCs. PMID:26514567

  10. Genistein as an inducer of tumor cell differentiation : possible mechanisms of action.

    SciTech Connect

    Constantinou, A.; Huberman, E.; Center for Mechanistic Biology and Biotechnology; Univ. of Illinois at Chicago

    1995-01-01

    Decreased activity of either topoisomerases or tyrosine kinases has been implicated in the differentiation of a number of cell types. It is therefore conceivable that genistein, because of its reported ability to inhibit these activities in vitro, may be an inducer of cellular differentiation. We investigated this possibility in human promyelocytic HL-60 and erythroid K-562 leukemia cells and in human SK-MEL-131 melanoma cells. Our results indicated that genistein, in a dose-dependent manner, inhibited cell multiplication and induced cell differentiation. The maturing HL-60 cells acquired granulocytic and monocytic markers. The differentiating K-562 cells stained positively with benzidine, which indicates the production of hemoglobin, an erythroid marker. Following genistein treatment, maturing SK-MEL-131 melanoma cells formed dendrite-like structures and exhibited increased tyrosinase activity and melanin content. Experiments were designed to identify the molecular mechanism of genistein's action. Data from our laboratory suggest that this isoflavone triggers the pathway that leads to cellular differentiation by stabilizing protein-linked DNA strand breakage. Other possible mechanisms reported in the literature are discussed.

  11. Differential effects of fluoxetine and venlafaxine on memory recognition: possible mechanisms of action.

    PubMed

    Carlini, Valeria Paola; Poretti, María Belén; Rask-Andersen, Mathias; Chavan, Rohit A; Ponzio, Marina F; Sawant, Rahul S; de Barioglio, Susana Rubiales; Schiöth, Helgi B; de Cuneo, Marta Fiol

    2012-08-01

    Serotonin-specific reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are antidepressant drugs commonly used to treat a wide spectrum of mood disorders (Wong and Licinio, 2001). Although they have been clinically used for more than 50 years, the molecular and cellular basis for the action of SSRIs and SNRIs is not clear. Considering that the changes in gene expression involved in the action of antidepressant drugs on memory have not been identified, in this study we investigated the impact of chronic treatment with a SSRI (fluoxetine) and a SNRI (venlafaxine) on the mRNA expression of genes related to memory cascade in the mouse hippocampus, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), nitric oxide synthase 1 (NOS1), neurotrophic tyrosine kinase receptor type 2 (TrKB), mitogen-activated protein kinases (MAPK/ERK) and serotonin transporter (SERT). Animals treated with fluoxetine 10 mg/Kg/day for 28 days showed a significant decrease in the percentage of time spent in the novel object recognition test (p≤0.005) and induced MAPK1/ERK2 down-regulation (p=0.005). Our results suggest that the effect on cognition could probably be explained by fluoxetine interference in the MAPK/ERK memory pathway. In contrast, chronic treatment with venlafaxine did not reduce MAPK1/ERK2 expression, suggesting that MAPK1/ERK2 down-regulation is not a common effect of all antidepressant drugs. Further studies are needed to examine the effect of chronic fluoxetine treatment on the ERK-CREB system, and to determine whether there is a causal relationship between the disruption of the ERK-CREB system and the effect of this antidepressant on memory performance. PMID:22449479

  12. Possible involvement of lipoic acid in binding protein-dependent transport systems in Escherichia coli.

    PubMed

    Richarme, G

    1985-04-01

    We describe the properties of the binding protein dependent-transport of ribose, galactose, and maltose and of the lactose permease, and the phosphoenolpyruvate-glucose phosphotransferase transport systems in a strain of Escherichia coli which is deficient in the synthesis of lipoic acid, a cofactor involved in alpha-keto acid dehydrogenation. Such a strain can grow in the absence of lipoic acid in minimal medium supplemented with acetate and succinate. Although the lactose permease and the phosphoenolypyruvate-glucose phosphotransferase are not affected by lipoic acid deprivation, the binding protein-dependent transports are reduced by 70% in conditions of lipoic acid deprivation when compared with their activity in conditions of lipoic acid supply. The remaining transport is not affected by arsenate but is inhibited by the uncoupler carbonylcyanide-m-chlorophenylhydrazone; however the lipoic acid-dependent transport is completely inhibited by arsenate and only weakly inhibited by carbonylcyanide-m-chlorophenylhydrazone. The known inhibitor of alpha-keto acid dehydrogenases, 5-methoxyindole-2-carboxylic acid, completely inhibits all binding protein-dependent transports whether in conditions of lipoic supply or deprivation; the results suggest a possible relation between binding protein-dependent transport and alpha-keto acid dehydrogenases and shed light on the inhibition of these transports by arsenicals and uncouplers. PMID:3920206

  13. Possible Involvement of Insulin Resistance in the Progression of Cancer Cachexia in Mice.

    PubMed

    Ohsawa, Masahiro; Murakami, Tomoyasu; Kume, Kazuhiko

    2016-01-01

    Malnutrition is a common problem among cancer patients, affecting up to 85% of patients with certain cancers. In severe cases, malnutrition can progress to cachexia, a specific form of malnutrition characterized by loss of lean body mass and muscle wasting. Although this muscle wasting might be a product of enhanced protein degradation, the precise mechanisms of cancer cachexia are not fully elucidated. Based on basic and clinical research, glucose intolerance and insulin resistance have been postulated to be associated with cancer cachexia. Since insulin in the skeletal muscle inhibits protein degradation and promotes protein synthesis, insulin resistance could be a possible cause of cancer cachexia. Therefore, we investigated the involvement of insulin resistance in the development of cancer cachexia in tumor-bearing mice. The signaling protein in the insulin cascade was attenuated in the skeletal muscle and hypothalamus from tumor-bearing mice. We identified Chrysanthemum morifolium RAMAT., known as Kikuka, as a peroxisome proliferator-activated receptor γ (PPARγ) ligand. Treatment with Kikuka attenuates the skeletal muscle changes in tumor-bearing mice. These results suggest that this natural PPARγ activator might be an attractive candidate for the treatment of cancer cachexia. In the symposium, we presented the PPARγ activator-induced improvement of cancer cachexia. PMID:27150920

  14. Possible involvement of tetrodotoxin-resistant sodium channels in cough reflex.

    PubMed

    Kamei, Junzo; Nakanishi, Yuki; Ishikawa, Yoko; Hayashi, Shun-Suke; Asato, Megumi; Ohsawa, Masahiro

    2011-02-10

    We examined the involvement of tetrodotoxin (TTX)-resistant sodium channels in the peripheral mechanisms of the cough reflex in mice. We also examined the possibility of using ambroxol as an effective antitussive agent, and found that it produced antitussive effects through the inhibition of TTX-resistant sodium channels. The inhalation of fenvalerate, at concentrations of 0.3, 1 and 3μg/ml, for 5min produced coughs in a concentration-dependent manner. Pretreatment with tetrodotoxin, at a dose of 1μg/kg, s.c., slightly but significantly reduced the number of fenvalerate (3μg/ml)-induced coughs. However, the number of fenvalerate-induced coughs in tetorodotoxin-treated mice was still significantly greater than those in vehicle (0.4% DMSO) alone inhaled mice. On the other hand, pretreatment with tetrodotoxin, at a dose of 1μg/kg, s.c., almost completely reduced the number of citric acid (0.25M)-induced coughs to the level in vehicle (saline) alone inhaled mice. Pretreatment with ambroxol, at doses of 10, 30, 100 and 300mg/kg, p.o., dose-dependently and significantly reduced the number of fenvalerate (3μg/ml)-induced coughs. The present findings indicate that TTX-resistant sodium channels may play an important role in the enhancement of C-fiber-mediated cough pathways. Furthermore, ambroxol may prove to be a useful cough suppressant. PMID:21130084

  15. Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action

    PubMed Central

    Taïwe, Germain Sotoing; Bum, Elisabeth Ngo; Talla, Emmanuel; Dimo, Théophile; Weiss, Norbert; Sidiki, Neteydji; Dawe, Amadou; Okomolo Moto, Fleur Clarisse; Dzeufiet, Paul Désiré; Waard, Michel De

    2011-01-01

    Context Nauclea latifolia Smith (Rubiacea) is a small tree, found in tropical areas in Africa. It is used in traditional medicine to treat malaria, epilepsy, anxiety, pain, fever etc. Objective The aim of this study was to investigate the effects of Nauclea latifolia roots decoction on the peripheral and central nervous systems and its possible mechanisms of action. Materials and methods The analgesic investigation was carried out against acetic acid-induced writhing, formalin-induced pain, hot-plate and tail immersion tests. The antipyretic activity was studied in Brewer’s yeast-induced pyrexia in mice. Rota-rod test and bicuculline-induced hyperactivity were used for the assessment of locomotor activity. Results Nauclea latifolia induced hypothermia and had antipyretic effects in mice. The plant decoction produced significant antinociceptive activity in all analgesia animal models used. The antinociceptive effect exhibited by the decoction in the formalin test was reversed by the systemic administration of naloxone, Nω-L-nitro-arginine methyl ester or glibenclamide. In contrast, theophylline did not reverse this effect. Nauclea latifolia (antinociceptive doses) did not exhibit significant effect on motor coordination of the mice in rota-rod performance. Nauclea latifolia protected mice against bicuculline-induced behavioural excitation. Discussion and conclusion Overall, these results demonstrate that the central and peripheral effects of Nauclea latifolia roots decoction might partially or wholly be due to the stimulation of peripheric opioid receptors through the action of the nitric oxide-cyclic GMP-ATP-sensitive K+ (NO/cGMP/ATP)-channel pathway and/or facilitation of the GABAergic transmission. PMID:20822326

  16. Cissus quadrangularis L. extract attenuates chronic ulcer by possible involvement of polyamines and proliferating cell nuclear antigen

    PubMed Central

    Jainu, Mallika; Vijaimohan, K.; Kannan, K.

    2010-01-01

    The present study was designed to investigate whether Cissus quandrangularis extract (CQE) had healing effects on gastric ulcer, through modulation of polyamines and proliferating cell nuclear antigen (PCNA) in rats. Administration of acetic acid (AA) was accompanied by reduced PCNA which was determined by immunohistochemical staining, 3H-thymidine incorporation using liquid scintillation spectrometry, mitochondrial marker enzymes, polyamine contents and transforming growth factor-alpha (TGF-α) expression in gastric mucosa of rats. Administration of CQE after the application of AA to the stomach enhanced the reduction of ulcer area in a dose-dependent manner which was confirmed by histoarchitecture. Moreover, CQE significantly increased the 3H-thymidine incorporation and the levels of polyamines such as putrescine, spermine and spermidine in ulcerated rats. In addition, the extract offers gastroprotection in the ulcerated area by increased expression of TGF-α and also reversed the changes in the gastric mucosa of ulcerated rats with significant elevation in mitochondrial tricarboxylic acid (TCA) cycle enzymes and PCNA levels. Based on these results, the healing effect of CQE on AA induced gastric mucosal injury in rats may be attributed to its growth promoting and cytoprotective actions, possibly involving an increase in tissue polyamine contents and cell proliferation. PMID:20931084

  17. Involvement of interleukin-1 in glial responses to lipopolysaccharide: endogenous versus exogenous interleukin-1 actions.

    PubMed

    Molina-Holgado, F; Toulmond, S; Rothwell, N J

    2000-11-01

    Interleukin-1beta (IL-1beta) participates in neuroinflammation and neurodegeneration. Its mechanisms of action are not fully understood, but appear to involve complex interactions between neurons and glia. The objective of this study was to determine the involvement of endogenous IL-1beta in inflammatory responses to LPS in cultured mouse glial cells, and compare this to the effects of exogenous IL-1beta. Activation of primary mixed glial cultures by incubation with LPS (1 microgram/ml, 24 h), caused marked (approximately ten-fold) increases in release of NO, twenty-fold increases in PGE(2) and ninety-fold increases of IL-6 release. Incubation with human recombinant IL-1beta (100 ng/ml) also stimulated NO and IL-6 release to a similar extent to LPS, but IL-1beta (1 or 100 ng/ml) caused only modest increases (approximately seven-fold) in PGE(2) release. Co-incubation with IL-1ra inhibited the effects of LPS on NO release (-65%) and IL-6 production (-30%), but failed to reduce PGE(2) release. These results indicate that exogenous IL-1beta induces release of NO, PGE(2) and IL-6 in mixed glial cultures, and that endogenous IL-1beta mediates inflammatory actions of LPS on NO and to a lesser extent IL-6, but not on PGE(2) release in mixed glial cultures. Indeed endogenous IL-1beta appears to inhibit LPS-induced PGE(2) release. PMID:11063815

  18. The action of neuropeptide AF on passive avoidance learning. Involvement of neurotransmitters.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Bagosi, Zsolt; Jászberényi, Miklós

    2016-01-01

    Neuropeptide AF (NPAF) is an amidated octadecapeptide, which is member of the RFamide peptide family. NPAF is encoded by the farp-1 gene and acts through the G protein coupled NPFF-1 and NPFF-2 receptors. NPAF is involved in several physiological functions of the central nervous system, however we have little evidence about the involvement of NPAF in learning and memory. Therefore, the aim of the present study was to investigate the action of NPAF on consolidation of memory in a passive avoidance learning paradigm in mice. We have also investigated the underlying neurotransmissions and the action of NPAF on β-amyloid-induced memory impairment. Accordingly, mice were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a non-selective opioid receptor antagonist, naloxone, a nitric oxide synthase inhibitor, nitro-l-arginine, a α1/α2β-adrenergic receptor antagonist, prazosin, a nonselective β-adrenergic receptor antagonist, propranolol or β-amyloid 25-35 in combination with NPAF administration. Our results demonstrate for the first time that NPAF improves the consolidation of passive avoidance learning. This effect is mediated through muscarinic cholinergic, 5HT1- and 5HT2-serotoninergic, dopaminergic, nitrergic and α- and β-adrenergic neurotransmissions, but not by opioid transmission, since atropine, cyproheptadine, methysergide, haloperidol, nitro-l-arginine, prazosin and propranolol reversed the action of NPAF, whereas naloxone was ineffective. The present study also shows that NPAF reverses the β-amyloid 25-35-induced memory impairment. PMID:26639667

  19. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors.

    PubMed

    Campos, Alline Cristina; Ferreira, Frederico Rogério; Guimarães, Francisco Silveira

    2012-11-01

    Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD. Male Wistar rats exposed to a predator (cat) received, 1 h later, singled or repeated i.p. administration of vehicle or CBD. Seven days after the stress animals were submitted to the elevated plus maze. To investigate the involvement of 5HT1A receptors in CBD effects animals were pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore possible neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and BDNF protein expression were measured in the hippocampus, frontal cortex, amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure. Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator exposure 5HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder. PMID:22979992

  20. Suppression of cell membrane permeability by suramin: involvement of its inhibitory actions on connexin 43 hemichannels

    PubMed Central

    Chi, Yuan; Gao, Kun; Zhang, Hui; Takeda, Masayuki; Yao, Jian

    2014-01-01

    BACKGROUND AND PURPOSE Suramin is a clinically prescribed drug for treatment of human African trypanosomiasis, cancer and infection. It is also a well-known pharmacological antagonist of P2 purinoceptors. Despite its clinical use and use in research, the biological actions of this molecule are still incompletely understood. Here, we investigated the effects of suramin on membrane channels, as exemplified by its actions on non-junctional connexin43 (Cx43) hemichannels, pore-forming α-haemolysin and channels involved in ATP release under hypotonic conditions. EXPERIMENTAL APPROACH Hemichannels were activated by removing extracellular Ca2+. The influences of suramin on hemichannel activities were evaluated by its effects on influx of fluorescent dyes and efflux of ATP. The membrane permeability and integrity were assessed through cellular retention of preloaded calcein and LDH release. KEY RESULTS Suramin blocked Cx43 hemichannel permeability induced by removal of extracellular Ca2+ without much effect on Cx43 expression and gap junctional intercellular communication. This action of suramin was mimicked by its analogue NF023 and NF449 but not by another P2 purinoceptor antagonist PPADS. Besides hemichannels, suramin also significantly blocked intracellular and extracellular exchanges of small molecules caused by α-haemolysin from Staphylococcus aureus and by exposure of cells to hypotonic solution. Furthermore, it prevented α-haemolysin- and hypotonic stress-elicited cell injury. CONCLUSION AND IMPLICATIONS Suramin blocked membrane channels and protected cells against toxin- and hypotonic stress-elicited injury. Our finding provides novel mechanistic insights into the pharmacological actions of suramin. Suramin might be therapeutically exploited to protect membrane integrity under certain pathological situations. PMID:24641330

  1. Aldrin-induced locomotor activity: possible involvement of the central GABAergic-cholinergic-dopaminergic interaction.

    PubMed

    Jamaluddin, S; Poddar, M K

    2001-01-01

    Aldrin (5 mg/kg/day, p.o.) under nontolerant condition, administered either for a single day or for 12 consecutive days, enhanced locomotor activity (LA) of rats. The increase in LA was greater in rats treated with aldrin for 12 consecutive days than that observed with a single dose. The aim of the present study is to evaluate the involvement of possible interactions of central GABAergic, cholinergic and dopaminergic systems using their agonist(s) and antagonist(s) in the regulation of LA in aldrin nontolerant rats. Administration of either L-DOPA along with carbidopa or bicuculline potentiated aldrin-induced increase in LA under nontolerant condition as well as LA of the control rats. Treatment with muscimol, haloperidol, atropine or physostigmine all decreased the LA of both aldrin nontolerant and control rats. Further, the application of (a) haloperidol along with bicuculline, atropine or physostigmine and (b) physostigmine along with bicuculline or L-DOPA + carbidopa significantly reduced LA but L-DOPA + carbidopa along with atropine or bicuculline increased LA of the control rats. These agonist(s)/antagonist(s)-induced decrease or increase in LA of the control rats were attenuated or potentiated, respectively, when those agonist(s)/antagonist(s) under abovementioned condition were administered to aldrin nontolerant rats. The attenuating or potentiating effects of aldrin on agonist(s)/antagonist(s) (either individually or in different combinations)-induced change in LA were greater in rats treated with aldrin for 12 consecutive days than that observed with a single-dose aldrin treatment. These results suggest that aldrin, under nontolerant condition, reduces central GABAergic activity and increases LA by activating dopaminergic system via inhibition of cholinergic activity. The treatment with aldrin for 12 consecutive days produces greater effect than that caused by a single-day treatment. PMID:11785907

  2. The enzymatic hydrolysis of pretreated pulp fibers predominantly involves “peeling/erosion” modes of action

    PubMed Central

    2014-01-01

    Background There is still considerable debate regarding the actual mechanism by which a “cellulase mixture” deconstructs cellulosic materials, with accessibility to the substrate at the microscopic level being one of the major restrictions that limits fast, complete cellulose hydrolysis. In the work reported here we tried to determine the predominant mode of action, at the fiber level, of how a cellulase mixture deconstructs pretreated softwood and hardwood pulp fibers. Quantitative changes in the pulp fibers derived from different pretreated biomass substrates were monitored throughout the course of enzymatic hydrolysis to see if the dominant mechanisms involved either the fragmentation/cutting of longer fibers to shorter fibers or their “peeling/delamination/erosion,” or if both cutting and peeling mechanisms occurred simultaneously. Results Regardless of the source of biomass, the type of pretreatment and the chemical composition of the substrate, under typical hydrolysis conditions (50°C, pH 4.8, mixing) longer pulp fibers (fiber length >200 μm) were rapidly broken down until a relatively constant fiber length of 130 to 160 μm was reached. In contrast, shorter fibers with an initial average fiber length of 130 to 160 μm showed no significant change in length despite their substantial hydrolysis. The fragmentation/cutting mode of deconstruction was only observed on longer fibers at early stages of hydrolysis. Although the fiber fragmentation mode of deconstruction was not greatly influenced by enzyme loading, it was significantly inhibited by glucose and was mainly observed during initial mixing of the enzyme and substrate. In contrast, significant changes in the fiber width occurred throughout the course of hydrolysis for all of the substrates, suggesting that fiber width may limit the rate and extent of cellulose hydrolysis. Conclusion It appears that, at the fiber level, pretreated pulp fibers are hydrolyzed through a two-step mode of action

  3. Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria.

    PubMed

    Perdigón, G; Vintiñi, E; Alvarez, S; Medina, M; Medici, M

    1999-06-01

    The induction of a mucosal immune response is not easy due to the development of oral tolerance, but under some conditions, bacteria can activate this immune system. Antigens administered orally can interact with M cells of Peyer's patches or bind to the epithelial cells. We have demonstrated that certain lactic acid bacteria are able to induce specific secretory immunity, and others will enhance the gut inflammatory immune response. The aim of this work was to establish the reason for these different behaviors and to define possible mechanisms involved in the interaction of lactic acid bacteria at the intestinal level. We studied IgA+ and IgM+ B cells comparatively in bronchus and intestine and CD4+ T cells and IgA anti-lactic acid bacteria antibodies in the intestinal fluid, induced by oral administration of Lactobacillus casei, Lb. delbrueckii ssp. bulgaricus, Lb. acidophilus, Lb. plantarum, Lb. rhamnosus, Lactococcus lactis, and Streptococcus salivarius ssp. thermophilus. The increase in the IgA+ B cells in the bronchus means that these lactic acid bacteria were able to induce the IgA cycle by interaction with M cells from Peyer's patches or intestinal epithelial cells. The IgM+ cells increased when the stimulus did not induce the switch from IgM+ to IgA+. The increase in the CD4+ cells suggests interaction of Peyer's patches and enhancement of the B- and T-cell migration. The anti-lactic acid bacteria antibody is related to the processing and presentation of the microorganisms to the immune cells. We demonstrated that Lb. casei and Lb. plantarum were able to interact with Peyer's patch cells and showed an increase in IgA-, CD4+ cells, and antibodies specific for the stimulating strain. Lactobacillus acidophilus induced gut mucosal activation by interaction with the epithelial cells without increase in the immune cells associated with the bronchus. Although Lb. rhamnosus and Strep. salivarius ssp. thermophilus interact with epithelial cells, they also induced

  4. Neuronal adaptation involves rapid expansion of the action potential initiation site.

    PubMed

    Scott, Ricardo S; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P; Rusakov, Dmitri A

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma-axon recordings combined with axonal Na(+) and Ca(2+) imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na(+) channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  5. Neuronal adaptation involves rapid expansion of the action potential initiation site

    PubMed Central

    Scott, Ricardo S.; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma–axon recordings combined with axonal Na+ and Ca2+ imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na+ channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  6. Immigrant Parent Involvement in U.S. Schools: Current Practices and Future Possibilities

    ERIC Educational Resources Information Center

    Aleixo, Marina Bandeira

    2012-01-01

    This dissertation examines how parent involvement expectations are communicated and enacted in interactions at one small urban high school. Through detailed descriptions of school interactions between supporting staff and immigrant parents, this study examines how parent involvement expectations are understood and perceived. Although scholarly…

  7. True User Involvement by People Living With HIV is Possible: Description of a User-driven HIV Clinic in Norway.

    PubMed

    Berg, Rigmor C; Gamst, Are; Said, Maryan; Aas, Kristin Bårdsen; Songe, Solveig Helene; Fangen, Kim; Rysstad, Ole

    2015-01-01

    The Greater Involvement of People Living with or Affected by HIV principle highlights the various contributions HIV-infected people can make in HIV program development and implementation. We present a unique example of how service users' involvement led to a complete organizational redesign of an outpatient HIV clinic in Southern Norway. We applied a user-driven, case study method, which showed that establishing a user board laid the foundation for the redesign process, as the board provided a clear infrastructure of user involvement and developed a set of user-defined targets for services. The main targets-optimal health, holistic care and treatment, and empowerment-were operationalized as a set of action points, such as establishing HIV nurse coordinators. While there is no single method for user involvement, we offer useful ideas that can help others develop an involvement project that is effective and sustainable. PMID:26255897

  8. Epigenetic regulation of the expression of genes involved in steroid hormone biosynthesis and action

    PubMed Central

    Martinez-Arguelles, Daniel B.; Papadopoulos, Vassilios

    2010-01-01

    Steroid hormones participate in organ development, reproduction, body homeostasis, and stress responses. The steroid machinery is expressed in a development- and tissue-specific manner, with the expression of these factors being tightly regulated by an array of transcription factors (TFs). Epigenetics provides an additional layer of gene regulation through DNA methylation and histone tail modifications. Evidence of epigenetic regulation of key steroidogenic enzymes is increasing, though this does not seem to be a predominant regulatory pathway. Steroid hormones exert their action in target tissues through steroid nuclear receptors belonging to the NR3A and NR3C families. Nuclear receptor expression levels and post-translational modifications regulate their function and dictate their sensitivity to steroid ligands. Nuclear receptors and TFs are more likely to be epigenetically regulated than proteins involved in steroidogenesis and have secondary impact on the expression of these steroidogenic enzymes. Here we review evidence for epigenetic regulation of enzymes, transcription factors, and nuclear receptors related to steroid biogenesis and action. PMID:20156469

  9. Involvement of μ-opioid receptors in antinociceptive action of botulinum toxin type A.

    PubMed

    Drinovac, V; Bach-Rojecky, L; Matak, I; Lacković, Z

    2013-07-01

    Botulinum toxin A (BTX-A) is approved for treatment of chronic migraine and has been investigated in various other painful conditions. Recent evidence demonstrated retrograde axonal transport and suggested the involvement of CNS in antinociceptive effect of BTX-A. However, the mechanism of BTX-A central antinociceptive action is unknown. In this study we investigated the potential role of opioid receptors in BTX-A's antinociceptive activity. In formalin-induced inflammatory pain we assessed the effect of opioid antagonists on antinociceptive activity of BTX-A. Naltrexone was injected subcutaneously (0.02-2 mg/kg) or intrathecally (0.07 μg/10 μl-350 μg/10 μl), while selective μ-antagonist naloxonazine was administered intraperitoneally (5 mg/kg) prior to nociceptive testing. The influence of naltrexone (2 mg/kg s.c.) on BTX-A antinociceptive activity was examined additionally in an experimental neuropathy induced by partial sciatic nerve transection. To investigate the effects of naltrexone and BTX-A on neuronal activation in spinal cord, c-Fos expression was immunohistochemically examined in a model of formalin-induced pain. Antinociceptive effects of BTX-A in formalin and sciatic nerve transection-induced pain were prevented by non-selective opioid antagonist naltrexone. Similarly, BTX-A-induced pain reduction was abolished by low dose of intrathecal naltrexone and by selective μ-antagonist naloxonazine. BTX-A-induced decrease in dorsal horn c-Fos expression was prevented by naltrexone. Prevention of BTX-A effects on pain and c-Fos expression by opioid antagonists suggest that the central antinociceptive action of BTX-A might be associated with the activity of endogenous opioid system (involving μ-opioid receptor). These results provide first insights into the mechanism of BTX-A's central antinociceptive activity. PMID:23499661

  10. Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways.

    PubMed

    Furukawa, K; Estus, S; Fu, W; Mark, R J; Mattson, M P

    1997-03-10

    The ability of the protein synthesis inhibitor cycloheximide (CHX) to prevent neuronal death in different paradigms has been interpreted to indicate that the cell death process requires synthesis of "killer" proteins. On the other hand, data indicate that neurotrophic factors protect neurons in the same death paradigms by inducing expression of neuroprotective gene products. We now provide evidence that in embryonic rat hippocampal cell cultures, CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including the antiapoptotic gene bcl-2 and antioxidant enzymes. Neuronal survival after exposure to glutamate, FeSO4, and amyloid beta-peptide was increased in cultures pretreated with CHX at concentrations of 50-500 nM; higher and lower concentrations were ineffective. Neuroprotective concentrations of CHX caused only a moderate (20-40%) reduction in overall protein synthesis, and induced an increase in c-fos, c-jun, and bcl-2 mRNAs and protein levels as determined by reverse transcription-PCR analysis and immunocytochemistry, respectively. At neuroprotective CHX concentrations, levels of c-fos heteronuclear RNA increased in parallel with c-fos mRNA, indicating that CHX acts by inducing transcription. Neuroprotective concentrations of CHX suppressed accumulation of H2O2 induced by FeSO4, suggesting activation of antioxidant pathways. Treatment of cultures with an antisense oligodeoxynucleotide directed against bcl-2 mRNA decreased Bcl-2 protein levels and significantly reduced the neuroprotective action of CHX, suggesting that induction of Bcl-2 expression was mechanistically involved in the neuroprotective actions of CHX. In addition, activity levels of the antioxidant enzymes Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and catalase were significantly increased in cultures exposed to neuroprotective levels of CHX. Our data suggest that low concentrations of CHX can promote neuron survival by

  11. Antimicrobial Activity of Ferulic Acid Against Cronobacter sakazakii and Possible Mechanism of Action.

    PubMed

    Shi, Chao; Zhang, Xiaorong; Sun, Yi; Yang, Miaochun; Song, Kaikuo; Zheng, Zhiwei; Chen, Yifei; Liu, Xin; Jia, Zhenyu; Dong, Rui; Cui, Lu; Xia, Xiaodong

    2016-04-01

    Cronobacter sakazakii is an opportunistic pathogen transmitted by food that affects mainly newborns, infants, and immune-compromised adults. In this study, the antibacterial activity of ferulic acid was tested against C. sakazakii strains. Minimum inhibitory concentration of ferulic acid against C. sakazakii strains was determined using the agar dilution method. Changes in intracellular pH, membrane potential and intracellular ATP concentration were measured to elucidate the possible antibacterial mechanism. Moreover, SYTO 9 nucleic acid staining was used to assess the effect of ferulic acid on bacterial membrane integrity. Cell morphology changes were observed under a field emission scanning electron microscope. The minimum inhibitory concentrations of ferulic acid against C. sakazakii strains ranged from 2.5 to 5.0 mg/mL. Addition of ferulic acid exerted an immediate and sustained inhibition of C. sakazakii proliferation. Ferulic acid affected the membrane integrity of C. sakazakii, as evidenced by intracellular ATP concentration decrease. Moreover, reduction of intracellular pH and cell membrane hyperpolarization were detected in C. sakazakii after exposure to ferulic acid. Reduction of green fluorescence indicated the injury of cell membrane. Electronic microscopy confirmed that cell membrane of C. sakazakii was damaged by ferulic acid. Our results demonstrate that ferulic acid has moderate antimicrobial activity against C. sakazakii. It exerts its antimicrobial action partly through causing cell membrane dysfunction and changes in cellular morphology. Considering its antimicrobial properties, together with its well-known nutritional functions, ferulic acid has potential to be developed as a supplement in infant formula or other foods to control C. sakazakii. PMID:26919471

  12. Parental Involvement in the Habilitation Process Following Children's Cochlear Implantation: An Action Theory Perspective

    ERIC Educational Resources Information Center

    Zaidman-Zait, Anat; Young, Richard A.

    2008-01-01

    Action theory and the qualitative action-project method are used in this study to address and illustrate the complexity of parenting children who have received cochlear implants (CIs) as well as the intentionality of parents engaged in that process. "Action" refers to individual and joint goal-directed and intentional behaviors. Action theory has…

  13. Genetic evidence for involvement of membrane trafficking in the action of 5-fluorouracil.

    PubMed

    Hu, Lingling; Yao, Fan; Ma, Yan; Liu, Qiannan; Chen, Si; Hayafuji, Tsutomu; Kuno, Takayoshi; Fang, Yue

    2016-08-01

    To identify novel genes that mediate cellular sensitivity and resistance to 5-fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Δryh1, Δric1, and Δaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action. PMID:27255861

  14. Involvement of the Motor System in Comprehension of Non-Literal Action Language: A Meta-Analysis Study.

    PubMed

    Yang, Jie; Shu, Hua

    2016-01-01

    Although numerous studies have shown that the sensory-motor system is involved in semantic processing of language stimuli, it is still unclear whether comprehension of abstract concepts is embodied, and whether the involvement of the sensory-motor system is context-dependent. Investigation of how the motor system is activated during comprehension of non-literal action languages can help address these issues. So far several studies have reported brain activations during non-literal action language comprehension, but the findings are highly inconsistent because of different types of non-literal action language stimuli. To clarify how the motor system is involved in comprehension of different types of non-literal languages, the current study conducted quantitative meta-analyses on fMRI findings about comprehension of sentences describing fictive motions, metaphoric actions, and idiomatic actions. Results showed that fictive motion sentences elicited activation in the right parahippocampal gyrus, an area important for spatial processing. For metaphoric actions, the left precentral gyrus (BA 6) was strongly activated, suggesting a link between metaphoric and literal meanings. For idiomatic actions, activity was found in the left inferior frontal gyrus (BA 44/45), highlighting semantic selection and inhibition. No premotor or motor activity was found in idiom condition. These results together suggest that the involvement of the sensory-motor system in abstract concepts processing is flexible, depending on semantic features of the language stimuli and links between abstract and literal meanings. PMID:25681159

  15. Participation of citral in the bronchodilatory effect of ginger oil and possible mechanism of action.

    PubMed

    Mangprayool, Thitiya; Kupittayanant, Sajeera; Chudapongse, Nuannoi

    2013-09-01

    The extract of ginger, the rhizomes of Zingiber officinale Roscoe (Zingiberaceae), has been reported to possess anti-hyperactivity and anti-inflammation on airway. The present study described brochodilatory activity of ginger oil and identified its active compound. Ginger oil was extracted by hydro-distillation. The compositions of ginger oil were analyzed by gas chromatography and mass spectrometer. Citral, eucalyptol and camphene were found to be the major components. Ginger oil and citral, but not camphene, suppressed rat tracheal contraction induced by carbachol (CCh). Consistent with previous report, eucalyptol showed a relaxing effect on rat airway. Since the content of eucalyptol in ginger oil was relatively low, the contribution of eucalyptol to the bronchodilatory effect of ginger oil was small. To elucidate the mechanisms responsible for the myorelaxing effect, propranolol (a β-adrenergic receptor antagonist), indomethacin (a COX inhibitor) and L-NAME (a NOS inhibitor) were used to block the inhibitory effects of ginger oil and citral. It was found that propranolol, but not indomethacin and L-NAME, reversed bronchodilatory effects of both ginger oil and citral, suggesting that a possible mechanism involved β-adrenergic receptor. This study provides the pharmacological basis supporting the therapeutic potential of Z. officinale rhizomes as a bronchodilator. PMID:23685048

  16. Δ9-Tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

    PubMed

    Takeda, Shuso

    2014-01-01

    Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects). Among Δ(9)-THC's biological activities, its recognized anti-estrogenic activity has been the subject of investigations. Since Δ(9)-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy in the United States and other countries (synthesized Δ(9)-THC; dronabinol), it is important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC. Since Δ(9)-THC has "no" binding potential for estrogen receptor α (ERα) which can be activated by estrogen (E2), the question of how Δ(9)-THC exerts its inhibitory effect on ERα is not resolved. We have recently reported that ERβ, a second type of ER, is involved in the Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well. PMID:25177025

  17. Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

    PubMed

    Acker, Corey D; Antic, Srdjan D

    2009-03-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  18. Involvement of the endogenous opioid system in the psychopharmacological actions of ethanol: the role of acetaldehyde

    PubMed Central

    Font, Laura; Luján, Miguel Á.; Pastor, Raúl

    2013-01-01

    Significant evidence implicates the endogenous opioid system (EOS) (opioid peptides and receptors) in the mechanisms underlying the psychopharmacological effects of ethanol. Ethanol modulates opioidergic signaling and function at different levels, including biosynthesis, release, and degradation of opioid peptides, as well as binding of endogenous ligands to opioid receptors. The role of β-endorphin and µ-opioid receptors (OR) have been suggested to be of particular importance in mediating some of the behavioral effects of ethanol, including psychomotor stimulation and sensitization, consumption and conditioned place preference (CPP). Ethanol increases the release of β-endorphin from the hypothalamic arcuate nucleus (NArc), which can modulate activity of other neurotransmitter systems such as mesolimbic dopamine (DA). The precise mechanism by which ethanol induces a release of β-endorphin, thereby inducing behavioral responses, remains to be elucidated. The present review summarizes accumulative data suggesting that the first metabolite of ethanol, the psychoactive compound acetaldehyde, could participate in such mechanism. Two lines of research involving acetaldehyde are reviewed: (1) implications of the formation of acetaldehyde in brain areas such as the NArc, with high expression of ethanol metabolizing enzymes and presence of cell bodies of endorphinic neurons and (2) the formation of condensation products between DA and acetaldehyde such as salsolinol, which exerts its actions via OR. PMID:23914161

  19. Social choice functions: A tool for ranking variables involved in action plans against road noise.

    PubMed

    Ruiz-Padillo, Alejandro; de Oliveira, Thiago B F; Alves, Matheus; Bazzan, Ana L C; Ruiz, Diego P

    2016-08-01

    Traffic noise is gaining importance in planning and operation of roads in developing countries, and particularly in Europe and Latin America. Many variables with different degrees of importance influence the perception of noise from roads. Thus, the problem of prioritizing road stretches for action against such noise is an important issue in environmental noise management. For example, it can be addressed using multicriteria methods. However, these methodologies require criteria or suitable variables to be ranked according to their relative importance. In the present study, for this ranking, a list of nine variables involved in the decision-making process (called "road stretch priority variables") was presented in the form of questionnaires to high-level experts from Andalusia, southern Spain. These experts ranked the variables by relevance. Using the same data, seven social choice functions (Plurality, Raynaud, Kemeny-Young, Copeland, Simpson, Schulze, and Borda) were used in order to rank the variables. The results indicate that the most important variables were those that take into account the parameters of greatest exposure for the citizens, followed by variables related to the intensity of the problem analyzed. The results show that a combination of the use of social choice functions on aggregated information from expert panels can provide a consensus for ranking priority variables related to road stretches. PMID:27127892

  20. Possible mechanism of psoralen phototoxicity not involving direct interaction with DNA

    SciTech Connect

    Laskin, J.D.; Lee, E.; Yurkow, E.J.; Laskin, D.L.; Gallo, M.A.

    1985-09-01

    Psoralens in combination with ultraviolet light (UVA; 320-400 nm) are used in the photochemical treatment of a variety of skin diseases including vitiligo, a skin depigmentational disorder, and psoriasis, a disease of accelerated epidermal cell proliferation. Although it is generally assumed that the major site of action of the psoralens is DNA, the authors have obtained evidence that another site may be the primary target for these compounds. They have identified specific, saturable, high-affinity binding sites for 8-methoxypsoralen on HeLa cells and have detected specific binding of 8-methoxypsoralen to four other human cell lines and five mouse cell lines. In HeLa cells, specific binding is reversible and independent of the ability of the compound to intercalate into DNA. In addition, binding sites become covalently modified by the psoralen after UVA exposure. Specific binding of 8-(methyoxy-/sup 3/H)methoxypsoralen constitutes 79% of the label bound to the cells. Scatchard analysis indicated two classes of psoralen binding sites. Based on these findings, the authors hypothesize that specific binding sites for psoralens on mammalian cells mediate, at least in part, psoralen-induced phototoxicity.

  1. Problems Teachers Face When Doing Action Research and Finding Possible Solutions: Three Cases

    ERIC Educational Resources Information Center

    Zhou, Jun

    2012-01-01

    Through case studies, this paper explores problems teachers face when doing action research: for instance, teachers may misunderstand the research, mistrust university researchers, lack the time or adequate library resources to conduct research, lack theoretical guidance or knowledge of research methodology, and feel pressure or frustration during…

  2. Automatic Imitation of Biomechanically Possible and Impossible Actions: Effects of Priming Movements versus Goals

    ERIC Educational Resources Information Center

    Longo, Matthew R.; Kosobud, Adam; Bertenthal, Bennett I.

    2008-01-01

    Recent behavioral, neuroimaging, and neurophysiological research suggests a common representational code mediating the observation and execution of actions; yet, the nature of this representational code is not well understood. The authors address this question by investigating (a) whether this observation-execution matching system (or mirror…

  3. OXIDATIVE STRESS AS A POSSIBLE MODE OF ACTION FOR ARSENIC CARCINOGENESIS

    EPA Science Inventory

    Abstract

    Many modes of action for arsenic carcinogenesis have been proposed, but few theories have a substantial mass of supporting data. Three stronger theories of arsenic carcinogenesis are production of chromosomal abnormalities, promotion of carcinogenesis and oxidati...

  4. Effect of diet and fenfluramine on thermogenesis in the rat: possible involvement of serotonergic mechanisms.

    PubMed

    Rothwell, N J; Stock, M J

    1987-01-01

    A single injection of 5-hydroxytryptamine (5HT, 1 mg/kg, s.c.) in rats stimulated resting oxygen consumption (Vo2) by 21 percent; this was reduced (to 8 percent) by pretreatment with hexamethonium (5 mg/kg, s.c.). DL-fenfluramine injection (20 mg/kg, s.c.) stimulated metabolic rate (Vo2) by about 40 percent, but caused only 11 and 15 per cent increases in animals pretreated with hexamethonium or metergoline (5 mg/kg, s.c.), respectively. Interscapular brown adipose tissue (BAT) activity, assessed from mitochondrial GDP-binding, was increased by 96 per cent in intact tissue 1 h after fenfluramine injection; this response was completely prevented by surgical sympathectomy of interscapular BAT. Metergoline significantly inhibited (by 46 percent) the acute thermic response (postprandial rise in Vo2) to a 40-kJ meal in normal rats, and depressed resting Vo2 in protein-deficient rats by 18 percent, but did not affect resting Vo2 in control animals. BAT activity (mitochondrial GDP-binding) was elevated by 56 per cent in rats fed the low-protein diet, but this difference was almost completely abolished by prior treatment with metergoline. These data demonstrate a potent thermogenic effect of fenfluramine which apparently involves serotonergic pathways and activation of sympathetic outflow to BAT, and indicate that acute thermic responses to food and chronic thermogenic responses to low-protein diets may also involve serotonergic mechanisms. PMID:3667065

  5. T-antigen binding lectin with antibacterial activity from marine invertebrate, sea cucumber (Holothuria scabra): possible involvement in differential recognition of bacteria.

    PubMed

    Gowda, Nagaraj M; Goswami, Usha; Khan, M Islam

    2008-10-01

    In invertebrates, cellular and humoral components are evolved to maintain their body immunity and integrity. Both these factors respond to different antigens such as microorganisms, vertebrate erythrocytes and foreign proteins. In this article, we report a study of a lectin (HSL) involved in immune response in the echinoderm, sea cucumber (Holothuria scabra). Correlative studies indicate that the expression of this defensive lectin is induced by bacterial challenge, wherein cell wall glycoconjugates of bacteria are involved in lectin induction. HSL showed strong broad spectrum antibacterial activity against both gram-positive and gram-negative bacteria. Under in vitro conditions, purified HSL mediate agglutination of the test bacteria, there by indicating a possible mode of action in physiological situation. PMID:18501924

  6. A possible collision involving the large main-belt asteroid (596) Schiela

    NASA Astrophysics Data System (ADS)

    Miles, R.

    2011-02-01

    On 2010 December 11.5, Steve Larson of the Lunar and Planetary Laboratory, University of Arizona, observing with the 0.68m f/1.8 Schmidt telescope of the Catalina Sky Survey, found that the minor planet (596) Scheila appeared to be exhibiting comet-like behaviour. This unique phenomenon is thought to be the result of a high-speed collision between Scheila (diameter ~113km) and a much smaller object, possibly some 10-100 metres across, orbiting in the outer regions of the Main Belt. The discovery was reported in Central Bureau Electronic Telegram no.2583 issued by the IAU on December 12.

  7. Biodegradation of ivory (natural apatite): possible involvement of fungal activity in biodeterioration of the Lewis Chessmen.

    PubMed

    Pinzari, Flavia; Tate, James; Bicchieri, Marina; Rhee, Young Joon; Gadd, Geoffrey Michael

    2013-04-01

    Fungal biodeterioration of ivory was investigated with in vitro inoculation of samples obtained from boar and walrus tusks with the fungi Aspergillus niger and Serpula himantioides, species of known geoactive abilities. A combination of light and scanning electron microscopy together with associated analytical techniques was used to characterize fungal interactions with the ivory, including changes in ivory composition, dissolution and tunnelling, and the formation of new biominerals. The research was aimed at providing further understanding of the potential roles of fungi in the colonization and deterioration of ivory in terrestrial environments, but also contributes to our knowledge regarding the possible origins of the surface damage observed on early medieval sculptures made largely from walrus tusks, referred to as 'the Lewis hoard of gaming pieces', that were presumably produced for playing chess. The experiments have shown that the possibility of damage to ivory being caused by fungi is realistic. Scanning electron microscopy revealed penetration of fungal hyphae within cracks in the walrus tusk that showed also widespread tunnelling by fungal hyphae as well as 'fungal footprints' where the surface was etched as a consequence of mycelial colonization. Similar phenomena were observed with boar tusk ivory, while production of metabolites could lead to complete dissolution of the sample. Colonization of ivory and/or exposure to fungal activity lead to extensive secondary biomineral formation, and this was identified as calcium oxalate, mainly as the monohydrate, whewellite. PMID:23157656

  8. A Gene Island with Two Possible Configurations Is Involved in Chromatic Acclimation in Marine Synechococcus

    PubMed Central

    Humily, Florian; Partensky, Frédéric; Six, Christophe; Farrant, Gregory K.; Ratin, Morgane; Marie, Dominique; Garczarek, Laurence

    2013-01-01

    Synechococcus, the second most abundant oxygenic phototroph in the marine environment, harbors the largest pigment diversity known within a single genus of cyanobacteria, allowing it to exploit a wide range of light niches. Some strains are capable of Type IV chromatic acclimation (CA4), a process by which cells can match the phycobilin content of their phycobilisomes to the ambient light quality. Here, we performed extensive genomic comparisons to explore the diversity of this process within the marine Synechococcus radiation. A specific gene island was identified in all CA4-performing strains, containing two genes (fciA/b) coding for possible transcriptional regulators and one gene coding for a phycobilin lyase. However, two distinct configurations of this cluster were observed, depending on the lineage. CA4-A islands contain the mpeZ gene, encoding a recently characterized phycoerythrobilin lyase-isomerase, and a third, small, possible regulator called fciC. In CA4-B islands, the lyase gene encodes an uncharacterized relative of MpeZ, called MpeW. While mpeZ is expressed more in blue light than green light, this is the reverse for mpeW, although only small phenotypic differences were found among chromatic acclimaters possessing either CA4 island type. This study provides novel insights into understanding both diversity and evolution of the CA4 process. PMID:24391958

  9. Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.

    PubMed

    Lin, Yan; Quartermain, David; Dunn, Adrian J; Weinshenker, David; Stone, Eric A

    2008-07-01

    alpha(1)-Adrenoceptors of the locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established. In addition to the canonical activation of alpha(1)-receptors by norepinephrine (NE), there is evidence that dopamine (DA) may also activate certain brain alpha(1)-receptors. This study examined the contribution of DA to exploratory activity in a novel cage by determining the effect of infusion of various dopaminergic and adrenergic drugs into the mouse LC. It was found that the D2/D3 agonist, quinpirole, which selectively blocks the release of CNS DA, produced a dose-dependent and virtually complete abolition of exploration and all movement in the novel cage test. The quinpirole-induced inactivity was significantly attenuated by coinfusion of DA but not by the D1 agonist, SKF38390. Furthermore, the DA attenuation of quinpirole inactivity was blocked by coinfusion of the alpha(1)-adrenergic receptor antagonist, terazosin, but not by the D1 receptor antagonist, SCH23390. LC infusions of either quinpirole or terazosin also produced profound inactivity in DA-beta-hydroxylase knockout (Dbh -/-) mice that lack NE, indicating that their behavioral effects were not due to an alteration of the release or action of LC NE. Measurement of endogenous DA, NE, and 5HT and their metabolites in the LC during exposure to the novel cage indicated an increase in the turnover of DA and NE but not 5HT. These results indicate that DA is a candidate as an endogenous agonist for behaviorally activating LC alpha(1)-receptors and may play a role in the activation of this nucleus by novel surroundings. PMID:18435418

  10. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    PubMed Central

    2011-01-01

    oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted. PMID:22185664

  11. Mastication dyspraxia: a neurodevelopmental disorder reflecting disruption of the cerebellocerebral network involved in planned actions.

    PubMed

    Mariën, Peter; Vidts, Annelies; Van Hecke, Wim; De Surgeloose, Didier; De Belder, Frank; Parizel, Paul M; Engelborghs, Sebastiaan; De Deyn, Peter P; Verhoeven, Jo

    2013-04-01

    cerebellocerebral network is crucially important in the planning and execution of skilled actions, but also seem to show for the first time that mastication deficits may be of true apraxic origin. As a result, it is hypothesized that "mastication dyspraxia" may have to be considered as a distinct nosological entity within the group of the developmental dyspraxias following a disruption of the cerebellocerebral network involved in planned actions. PMID:23065651

  12. Vesicular trafficking in characean green algae and the possible involvement of a VAMP72-family protein

    PubMed Central

    Hoepflinger, Marion C; Hametner, Christina; Ueda, Takashi; Foissner, Ilse

    2014-01-01

    The RAB5 GTPase ARA6 of Arabidopsis thaliana is known to be involved in endosomal trafficking by targeting vesicles to the plasma membrane. During this process AtARA6 is working in close relationship with the SNARE protein VAMP727 (vesicle associated membrane protein 727). Recently, ARA6 of the characean green algae Chara australis (CaARA6) was shown to have properties similar to AtARA6, pointing to similar trafficking pathways. In order to gain further insight into the vesicle trafficking machinery of Characeae, C. australis was analyzed for homologous proteins of the VAMP72-family. A CaVAMP72 protein was detected and classified by protein sequence alignment and phylogenetic analyses. PMID:24614164

  13. Vesicular trafficking in characean green algae and the possible involvement of a VAMP72-family protein.

    PubMed

    Hoepflinger, Marion C; Hametner, Christina; Ueda, Takashi; Foissner, Ilse

    2014-01-01

    The RAB5 GTPase ARA6 of Arabidopsis thaliana is known to be involved in endosomal trafficking by targeting vesicles to the plasma membrane. During this process AtARA6 is working in close relationship with the SNARE protein VAMP727 (vesicle associated membrane protein 727). Recently, ARA6 of the characean green algae Chara australis (CaARA6) was shown to have properties similar to AtARA6, pointing to similar trafficking pathways. In order to gain further insight into the vesicle trafficking machinery of Characeae, C. australis was analyzed for homologous proteins of the VAMP72-family. A CaVAMP72 protein was detected and classified by protein sequence alignment and phylogenetic analyses. PMID:25764429

  14. Vesicular trafficking in characean green algae and the possible involvement of a VAMP72-family protein.

    PubMed

    Hoepflinger, Marion; Hametner, Christina; Ueda, Takashi; Foissner, Ilse

    2014-01-01

    The RAB5 GTPase ARA6 (AtARA6) of Arabidopsis thaliana is known to be involved in endosomal trafficking by targeting vesicles to the plasma membrane. During this process AtARA6 is working in close relationship with the SNARE protein VAMP727 (vesicle associated membrane protein 727). Recently, ARA6 of the characean green algae Chara australis (CaARA6) was shown to have properties similar to AtARA6, pointing to similar trafficking pathways. In order to gain further insight into the vesicle trafficking machinery of characeae, C. australis was analyzed for homologous proteins of the VAMP72-family. A CaVAMP72 protein was detected and classified by protein sequence alignment and phylogenetic analyses. PMID:24614164

  15. Brachial Neuritis With Phrenic Nerve Involvement in a Patient With a Possible Connective Tissue Disease

    PubMed Central

    Subash, Meera; Patel, Gaurav; Welker, John

    2014-01-01

    Background. Brachial neuritis (BN) is a rare inflammatory condition of peripheral nerves, usually involving the cervicobrachial plexus. These patients present with sudden onset of shoulder and arm pain that evolves into muscle weakness and atrophy.. Case Report. A 33-year-old woman presented with a 1-month history of diffuse pain in her thorax. She had no trauma or inciting incident prior to the onset of this pain and was initially treated for muscle spasms. The patient was seen in the emergency room multiple times and was treated with several courses of antibiotics for pneumonia on the basis of clinical symptoms and abnormal x-rays. The pleuritic chest pain persisted for at least 4 months, and the patient was eventually admitted for worsening pain and dyspnea. On physical examination, crackles were heard at both lung bases, and chest inspection revealed increased expansion in the upper thorax but poor expansion of the lower thorax and mild paradoxical respiration. “Sniff” test revealed no motion of the left hemidiaphragm and reduced motion on the right hemidiaphragm. Her computed tomography scan revealed bilateral atelectasis, more severe at the left base. She reported no symptoms involving her joints or skin or abdomen. Her presentation and clinical course are best explained by BN with a bilateral diaphragmatic weakness. However, she had a positive ANA, RF, anti-RNP antibody, and anti SS-A. Conclusion. Patients with BN can present with diffuse thoracic pain, pleuritic chest pain, and diaphragmatic weakness. Our patient may represent a case of connective tissue disease presenting with brachial plexus neuritis. PMID:26425609

  16. Possible involvement of miRNAs in tropism of Parvovirus B19.

    PubMed

    Anbarlou, Azadeh; AkhavanRahnama, Mahshid; Atashi, Amir; Soleimani, Masoud; Arefian, Ehsan; Gallinella, Giorgio

    2016-03-01

    Human Parvovirus B19 (PVB19) is one of the most important pathogens that targets erythroid lineage. Many factors were mentioned for restriction to erythroid progenitor cells (EPCs). Previous studies showed that in non-permissive cells VP1 and VP2 (structural proteins) mRNAs were detected but could not translate to proteins. A bioinformatics study showed that this inhibition might be due to specific microRNAs (miRNAs) present in non-permissive cells but not in permissive EPCs. To confirm the hypothesis, we evaluated the effect of miRNAs on VP expression. CD34(+) HSCs were separated from cord blood. Then, CD34(+) cells were treated with differentiation medium to obtain CD36(+) EPCs. To evaluate the effect of miRNAs on VP expression in MCF7 and HEK-293 cell lines (non-permissive cells) and CD36(+) EPCs, dual luciferase assay was performed in presence of shRNAs against Dicer and Drosha to disrupt miRNA biogenesis. QRT-PCR was performed to check down-regulation of Dicer and Drosha after transfection. All measurements were done in triplicate. Data means were compared using one-way ANOVAs. MicroRNA prediction was done by the online microRNA prediction tools. No significant difference was shown in luciferase activity of CD36(+) EPCs after co-transfection with shRNAs, while it was significant in non-permissive cells. Our study revealed that miRNAs may be involved in inhibition of VP expression in non-permissive cells, although further studies are required to demonstrate which miRNAs exactly are involved in regulation of PVB19 replication. PMID:26878856

  17. Brachial Neuritis With Phrenic Nerve Involvement in a Patient With a Possible Connective Tissue Disease.

    PubMed

    Subash, Meera; Patel, Gaurav; Welker, John; Nugent, Kenneth

    2014-01-01

    Background. Brachial neuritis (BN) is a rare inflammatory condition of peripheral nerves, usually involving the cervicobrachial plexus. These patients present with sudden onset of shoulder and arm pain that evolves into muscle weakness and atrophy.. Case Report. A 33-year-old woman presented with a 1-month history of diffuse pain in her thorax. She had no trauma or inciting incident prior to the onset of this pain and was initially treated for muscle spasms. The patient was seen in the emergency room multiple times and was treated with several courses of antibiotics for pneumonia on the basis of clinical symptoms and abnormal x-rays. The pleuritic chest pain persisted for at least 4 months, and the patient was eventually admitted for worsening pain and dyspnea. On physical examination, crackles were heard at both lung bases, and chest inspection revealed increased expansion in the upper thorax but poor expansion of the lower thorax and mild paradoxical respiration. "Sniff" test revealed no motion of the left hemidiaphragm and reduced motion on the right hemidiaphragm. Her computed tomography scan revealed bilateral atelectasis, more severe at the left base. She reported no symptoms involving her joints or skin or abdomen. Her presentation and clinical course are best explained by BN with a bilateral diaphragmatic weakness. However, she had a positive ANA, RF, anti-RNP antibody, and anti SS-A. Conclusion. Patients with BN can present with diffuse thoracic pain, pleuritic chest pain, and diaphragmatic weakness. Our patient may represent a case of connective tissue disease presenting with brachial plexus neuritis. PMID:26425609

  18. Possible involvement of Pseudomonas fluorescens and Bacillaceae in structural modifications of Tuber borchii fruit bodies.

    PubMed

    Citterio, B; Malatesta, M; Battistelli, S; Marcheggiani, F; Baffone, W; Saltarelli, R; Stocchi, V; Gazzanelli, G

    2001-03-01

    Previous studies on Tuber borchii fruit bodies in early maturation stages suggested a role of bacteria in sporocarp structural modifications. In order to verify this hypothesis, in the present study we investigated by means of microbial and ultrastructural approaches, the bacterial population of T. borchii sporocarps from intermediate maturation phases to advanced decomposition stages, paying particular attention to chitinolytic and cellulolytic bacteria and to their relationships with ascii and ascospores. We found that Pseudomonas fluorescens and spore-forming Bacillaceae, both able to degrade cellulose and chitin, are present inside the sporocarps in all maturation stages investigated. Moreover, rod-shaped bacteria seem able to erode ascus walls and colonize the interior of ascii containing mature spores. These results suggest a possible role of these bacteria in the process of ascus opening. Moreover, the presence of P. fluorescens and Bacillaceae on isolated mature spores after decontamination suggests an intimate association between these bacteria and the ascospores. PMID:11315117

  19. Cholinergic neurotransmission seems not to be involved in depression but possibly in personality.

    PubMed Central

    Fritze, J; Lanczik, M; Sofic, E; Struck, M; Riederer, P

    1995-01-01

    Concordant with the adrenergic-cholinergic imbalance hypothesis of affective psychosis, there is a cholinergic supersensitivity in depression. Thus, the anticholinergic properties of some antidepressants might contribute to their efficacy. However, in the present double-blind studies (n = 20) with mianserin and viloxazine, respectively, which lack anticholinergic properties, adjunctive treatment with the anticholinergic biperiden versus placebo did not enhance the antidepressive efficacy. Therefore, we hypothesized that cholinergic supersensitivity might be linked to some possibly predisposing dimension of personality. Indeed, in healthy male volunteers (n = 11) the behavioral and cardiovascular sensitivity to physostigmine correlated significantly with "irritability" and "emotional lability" as well as with habitually passive strategies in stress coping. The rise in plasma cortisol and norepinephrine correlated with "retardation"; that of epinephrine with active coping. Thus, the cholinergic supersensitivity in affective psychoses might be linked to a personality dimension like stress sensitivity rather than to the diagnostic category itself. Images Fig. 2 PMID:7865500

  20. The sequential encoding of competing action goals involves dynamic restructuring of motor plans in working memory.

    PubMed

    Gallivan, Jason P; Bowman, Natasha A R; Chapman, Craig S; Wolpert, Daniel M; Flanagan, J Randall

    2016-06-01

    Recent neural and behavioral findings provide support for the influential idea that in situations in which multiple action options are presented simultaneously, we prepare action plans for each competing option before deciding between and executing one of those plans. However, in natural, everyday environments, our available action options frequently change from one moment to the next, and there is often uncertainty as to whether additional options will become available before having to select a particular course of action. Here, with the use of a target-directed reaching task, we show that in this situation, the brain specifies a competing action for each new, sequentially presented potential target and that recently formed action plans can be revisited and updated so as to conform with separate, more newly developed, plans. These findings indicate that the brain forms labile motor plans for sequentially arising target options that can be flexibly restructured to accommodate new motor plans. PMID:27030738

  1. Cell signaling and estrogens in female rat osteoblasts: a possible involvement of unconventional nonnuclear receptors.

    PubMed

    Lieberherr, M; Grosse, B; Kachkache, M; Balsan, S

    1993-11-01

    Estrogen deficiency is associated with bone loss, and estrogen replacement is an effective treatment of this osteoporotic process. This study examines the early (5-120 s) effects of 17 beta-estradiol on the intracellular calcium and phospholipid metabolism in confluent female rat osteoblasts. The cytosolic free Ca2+ concentration ([Ca2+]i) was determined using fura-2/AM as Ca2+ probe. Cells were labeled with myo-[2-3H]inositol or [14C]arachidonic acid for inositol or lipid determination. Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) production were determined by either mass measurement or anion-exchange chromatography or by thin-layer chromatography, respectively. 17 beta-Estradiol (1 pM to 1 nM) increased [Ca2+]i in a biphasic manner within 10 s via Ca2+ influx from the extracellular milieu, as shown by the effects of the calcium chelator EGTA and the Ca2+ channel blockers nifedipine and verapamil, and via Ca2+ mobilization from the endoplasmic reticulum (ER), as shown by the effects of thapsigargin. 17 beta-Estradiol (1 pM to 1 nM) induced a biphasic and concomitant increase in IP3 and DAG formation. Estradiol immobilized on bovine serum albumin (BSA) [E-(O-carboxymethyl)oxime BSA] and its derivative (O-carboxymethyl)oxime rapidly increased ([Ca2+]i, IP3, and DAG and were full agonists, although they were less potent than the free estradiol. They had the same action time course and acted via Ca2+ influx and Ca2+ mobilization from ER. Tamoxifen, a potent inhibitor of genomic steroid responses, did not block the rapid increase in Ca2+, IP3, and DAG induced by estradiol. Finally, inhibitor of phospholipase C (neomycin) and pertussis toxin abolished the effects of 17 beta-estradiol on IP3 and DAG formation. These results suggest that female rat osteoblasts bear non-genomic unconventional cell surface receptors for estradiol, belonging to the class of the membrane receptors coupled to a phospholipase C via a pertussis toxin-sensitive G protein. PMID

  2. Possible mechanisms of action of mushroom-derived glucans on inflammatory bowel disease and associated cancer

    PubMed Central

    Hadar, Yitzhak

    2014-01-01

    Since ancient times, medicinal mushrooms have been traditionally used as a health food or supplement for the prevention and cure of a range of health-statuses or diseases, such as overt inflammation, atherosclerosis, cancer, hypertension, diabetes and others. We concentrate in this review on the effect and putative mechanism of action of glucans harvested from fungi on inflammatory bowel disease (IBD) and colitis associated cancer. Many scientists including our own group have examined the immunomodulating effect of isolated polysaccharides-glucans in general and specifically in inflammation associated with cancer. In this manuscript we reviewed the sources, the chemical composition and medicinal properties of polysaccharides extracted from edible mushrooms. In addition we brought insights into their putative mechanisms of action behind each health-promoting activity of these interesting biomolecules. The preventive and therapeutic effects of the medicinal mushrooms and their components have been well documented in mouse and rat model systems and in cancer cell lines being the most striking effects reported to their anti-inflammatory and antitumor effect. Their anticancer effects were demonstrated mainly in in vitro and in vivo experimental systems but a very limited number of studies have been conducted in human populations. We can summarize that oral consumption of several mushrooms glucans is an efficient treatment to prevent colitis-associated dysplasias through modulation of mucosal inflammation and cell proliferation. Identifying new food-derived isolates and understanding their mechanisms of action are the main challenges in using mushrooms glucans for therapeutic purposes in the field of IBD and associated cancer. Only an in-depth understanding of the mechanism of action and cross-talk between the inflammatory cell, epithelial cell and fungi derived glucans on which we have a based structural knowledge will lead to well designed intervention clinical human

  3. The possibility of laser action in ionic heteronuclear molecules. I - Spectroscopy. II - Kinetics

    NASA Astrophysics Data System (ADS)

    Basov, N. G.; Voitik, M. G.; Zuev, V. S.; Kutakhov, V. P.

    1985-11-01

    A theoretical study is presented of the electronic structure of levels of ionic heteronuclear molecules (IHM) consisting of atoms and ions of inert gases, halogens, the oxygen group, and alkali metals. Electron transitions are found which are promising for the generation of laser action in the visible, UV, and far UV (greater than 70 nm). In addition, the feasibility of a new family of IHM gas lasers emitting in the above-mentioned ranges is demonstrated theoretically.

  4. Possible mechanisms of action of mushroom-derived glucans on inflammatory bowel disease and associated cancer.

    PubMed

    Schwartz, Betty; Hadar, Yitzhak

    2014-02-01

    Since ancient times, medicinal mushrooms have been traditionally used as a health food or supplement for the prevention and cure of a range of health-statuses or diseases, such as overt inflammation, atherosclerosis, cancer, hypertension, diabetes and others. We concentrate in this review on the effect and putative mechanism of action of glucans harvested from fungi on inflammatory bowel disease (IBD) and colitis associated cancer. Many scientists including our own group have examined the immunomodulating effect of isolated polysaccharides-glucans in general and specifically in inflammation associated with cancer. In this manuscript we reviewed the sources, the chemical composition and medicinal properties of polysaccharides extracted from edible mushrooms. In addition we brought insights into their putative mechanisms of action behind each health-promoting activity of these interesting biomolecules. The preventive and therapeutic effects of the medicinal mushrooms and their components have been well documented in mouse and rat model systems and in cancer cell lines being the most striking effects reported to their anti-inflammatory and antitumor effect. Their anticancer effects were demonstrated mainly in in vitro and in vivo experimental systems but a very limited number of studies have been conducted in human populations. We can summarize that oral consumption of several mushrooms glucans is an efficient treatment to prevent colitis-associated dysplasias through modulation of mucosal inflammation and cell proliferation. Identifying new food-derived isolates and understanding their mechanisms of action are the main challenges in using mushrooms glucans for therapeutic purposes in the field of IBD and associated cancer. Only an in-depth understanding of the mechanism of action and cross-talk between the inflammatory cell, epithelial cell and fungi derived glucans on which we have a based structural knowledge will lead to well designed intervention clinical human

  5. [Possible involvement of Epstein-Barr virus in the pathogenesis of Sjögren's syndrome].

    PubMed

    Haruta, J; Saito, I

    1995-10-01

    Research into the role of Epstein-Barr virus (EBV) in the pathogenesis of SS has been a focus of interest for the past decade. The use of EBV as a probe for cellular and humoral immune responses has contributed to our current understanding of SS. However, it is still difficult to assign a role to EBV in the pathogenesis of SS. We have already demonstrated a) increased excretion of EBV in the saliva of SS, increased levels of EBV DNA in salivary gland biopsies of SS patients and spontaneous and massive production of transforming EBV in B cell lines established from SS patients. These data suggest that the reactivation of EBV might be deeply involved in disease perpetuation, polyclonal B cell activation and B cell malignancy in SS, even if it is not the primary cause. Recently, we examined the nucleotide sequence of the U2 region in EBV obtained from SS patients. The U2 region contains genes encoding EBNA-2, which plays an important role in B cell transformation and activation. In addition, studies on the breakdown of self-tolerance, and intriguing evidence supporting a potential role for infectious agents such as EBV and retroviruses also offer novel views of inflammation of salivary gland. This review will discuss recent advances in these subjects. PMID:8531359

  6. Possible involvement of histamine, dopamine, and noradrenalin in the periaqueductal gray in electroacupuncture pain relief.

    PubMed

    Murotani, Tomotaka; Ishizuka, Tomoko; Nakazawa, Hiroyuki; Wang, Xiaoming; Mori, Kazu; Sasaki, Kazuro; Ishida, Torao; Yamatodani, Atsushi

    2010-01-01

    Acupuncture and electroacupuncture are used in pain relief; however, the mechanism underlying the analgesic effect of acupuncture is unclear. Several lines of evidence propose that the periaqueductal gray (PAG), which is one of the regions that contributes to the endogenous pain inhibitory system, is involved in the analgesic effect of acupuncture, and the region receives several neural projections such as histamine and noradrenalin and contains the dopamine cell bodies. The current study examined the effects of electroacupuncture at Zusanli (ST36) and Shangjuxu (ST37) acupoints, which are used for clinical pain control, on the release of neurotransmitters in the PAG in rats. Histamine and dopamine release was increased after pain stimulus, while the changes were completely abolished by electroacupuncture. Pain stimulus had no effect on noradrenalin release, but electroacupuncture increased its release. These findings indicate that acupuncture at Zusanli and Shangjuxu exerts an antinociceptive effect via the activation of neurons in the PAG and that the histaminergic, dopaminergic, and noradrenalinergic systems in the PAG are related to electroacupuncture-induced pain relief. PMID:19819232

  7. Possible involvement of Escherichia coli 23S ribosomal RNA in peptide bond formation.

    PubMed Central

    Nitta, I; Ueda, T; Watanabe, K

    1998-01-01

    Experimental results are presented suggesting that 23S rRNA is directly involved in the peptide bond formation usually performed on the ribosome. Although several reports have indicated that the eubacterial peptidyltransferase reaction does not necessarily require all the ribosomal proteins, the reconstitution of peptidyltransferase activity by a naked 23S rRNA without the help of any of the ribosomal proteins has not been reported previously. It is demonstrated that an E. coli 23S rRNA transcript synthesized by T7 RNA polymerase in vitro was able to promote peptide bond formation in the presence of 0.5% SDS. The reaction was inhibited by the peptidyltransferase-specific antibiotics chloramphenicol and carbomycin, and by digestion with RNases A and T1. Site-directed mutageneses at two highly conserved regions close to the peptidyltransferase center ring, G2252 to U2252 and C2507G2581 to U2507A2581, also suppressed peptide bond formation. These findings strongly suggest that 23S rRNA is the peptidyltransferase itself. PMID:9510328

  8. Oxytocin is involved in the proconvulsant effects of Sildenafil: Possible role of CREB.

    PubMed

    Khoshneviszadeh, Mahsima; Rahimian, Reza; Fakhfouri, Gohar; Payandemehr, Borna; Khodagholi, Fariba; Ejtemaei Mehr, Shahram; Dehpour, Ahmad Reza

    2016-08-10

    Sildenafil is a phosphodiesterase type 5 inhibitor mainly used for male erectile dysfunction. One of rare yet serious adverse effects of Sildenafil is its potential to decrease seizure threshold. Ample evidence suggests that Sildenafil exerts central effects through induction of Oxytocin (OT) secretion and CREB phosphorylation. The aim of the present study is to evaluate potential roles of OT and CREB in the proconvulsant effects of Sildenafil. The Pentylenetetrazole-induced seizure was used as a standard convulsion model in this study. OT release and pCREB expression were evaluated in the hippocampus of mice using ELISA and western blot assays, respectively. Our results showed that Sildenafil at the dose of 10mgkg(-1) or higher, significantly decreased seizure threshold. Pretreatment with a non-effective dose of OT, potentiated while OT receptor antagonist, Atosiban, reversed fully the proconvulsant effects of Sildenafil (5mgkg(-1)). At biochemical inspection, Sildenafil markedly increased CREB which was attenuated by coadministration of Atosiban. The present study shows for the first time that OT release and the subsequent CREB phosphorylation are involved in the proconvulsant effects of acute Sildenafil treatment in an experimental model of seizure. PMID:27220266

  9. Involvement of Ethylene in the Action of the Cotton Defoliant Thidiazuron 1

    PubMed Central

    Suttle, Jeffrey C.

    1985-01-01

    The effect of the defoliant thidiazuron (N-phenyl-N′-1,2,3-thiadiazol-5-ylurea) on endogenous ethylene evolution and the role of endogenous ethylene in thidiazuron-mediated leaf abscission were examined in cotton (Gossypium hirsutum L. cv Stoneville 519) seedlings. Treatment of 20- to 30-day-old seedlings with thidiazuron at concentrations equal to or greater than 10 micromolar resulted in leaf abscission. At a treatment concentration of 100 micromolar, nearly total abscission of the youngest leaves was observed. Following treatment, abscission of the younger leaves commenced within 48 hours and was complete by 120 hours. A large increase in ethylene evolution from leaf blades and abscission zone explants was readily detectable within 24 hours of treatment and persisted until leaf fall. Ethylene evolution from treated leaf blades was greatest 1 day posttreatment and reached levels in excess of 600 nanoliters per gram fresh weight per hour (26.7 nanomoles per gram fresh weight per hour). The increase in ethylene evolution occurred in the absence of increased ethane evolution, altered leaf water potential, or decreased chlorophyll levels. Treatment of seedlings with inhibitors of ethylene action (silver thiosulfate, hypobaric pressure) or ethylene synthesis (aminoethoxyvinylglycine) resulted in an inhibition of thidiazuron-induced defoliation. Application of exogenous ethylene or 1-aminocyclopropane-1-carboxylic acid largely restored the thidiazuron response. The results indicate that thidiazuron-induced leaf abscission is mediated, at least in part, by an increase in endogenous ethylene evolution. However, alterations of other phytohormone systems thought to be involved in regulating leaf abscission are not excluded by these studies. PMID:16664229

  10. Involvement of ethylene in the action of the cotton defoliant thidiazuron.

    PubMed

    Suttle, J C

    1985-06-01

    The effect of the defoliant thidiazuron (N-phenyl-N'-1,2,3-thiadiazol-5-ylurea) on endogenous ethylene evolution and the role of endogenous ethylene in thidiazuron-mediated leaf abscission were examined in cotton (Gossypium hirsutum L. cv Stoneville 519) seedlings. Treatment of 20- to 30-day-old seedlings with thidiazuron at concentrations equal to or greater than 10 micromolar resulted in leaf abscission. At a treatment concentration of 100 micromolar, nearly total abscission of the youngest leaves was observed. Following treatment, abscission of the younger leaves commenced within 48 hours and was complete by 120 hours. A large increase in ethylene evolution from leaf blades and abscission zone explants was readily detectable within 24 hours of treatment and persisted until leaf fall. Ethylene evolution from treated leaf blades was greatest 1 day posttreatment and reached levels in excess of 600 nanoliters per gram fresh weight per hour (26.7 nanomoles per gram fresh weight per hour). The increase in ethylene evolution occurred in the absence of increased ethane evolution, altered leaf water potential, or decreased chlorophyll levels. Treatment of seedlings with inhibitors of ethylene action (silver thiosulfate, hypobaric pressure) or ethylene synthesis (aminoethoxyvinylglycine) resulted in an inhibition of thidiazuron-induced defoliation. Application of exogenous ethylene or 1-aminocyclopropane-1-carboxylic acid largely restored the thidiazuron response. The results indicate that thidiazuron-induced leaf abscission is mediated, at least in part, by an increase in endogenous ethylene evolution. However, alterations of other phytohormone systems thought to be involved in regulating leaf abscission are not excluded by these studies. PMID:16664229

  11. CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer.

    PubMed

    Banin-Hirata, Bruna Karina; Losi-Guembarovski, Roberta; Oda, Julie Massayo Maeda; de Oliveira, Carlos Eduardo Coral; Campos, Clodoaldo Zago; Mazzuco, Tânia Longo; Borelli, Sueli Donizete; Ceribelli, Jesus Roberto; Watanabe, Maria Angelica Ehara

    2016-05-01

    Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation. PMID:25716470

  12. Lithium inhibits invasion of glioma cells; possible involvement of glycogen synthase kinase-3

    PubMed Central

    Nowicki, Michal O.; Dmitrieva, Nina; Stein, Andrew M.; Cutter, Jennifer L.; Godlewski, Jakub; Saeki, Yoshinaga; Nita, Masayuki; Berens, Michael E.; Sander, Leonard M.; Newton, Herbert B.; Chiocca, E. Antonio; Lawler, Sean

    2008-01-01

    Therapies targeting glioma cells that diffusely infiltrate normal brain are highly sought after. Our aim was to identify novel approaches to this problem using glioma spheroid migration assays. Lithium, a currently approved drug for the treatment of bipolar illnesses, has not been previously examined in the context of glioma migration. We found that lithium treatment potently blocked glioma cell migration in spheroid, wound-healing, and brain slice assays. The effects observed were dose dependent and reversible, and worked using every glioma cell line tested. In addition, there was little effect on cell viability at lithium concentrations that inhibit migration, showing that this is a specific effect. Lithium treatment was associated with a marked change in cell morphology, with cells retracting the long extensions at their leading edge. Examination of known targets of lithium showed that inositol monophosphatase inhibition had no effect on glioma migration, whereas inhibition of glycogen synthase kinase-3 (GSK-3) did. This suggested that the effects of lithium on glioma cell migration could possibly be mediated through GSK-3. Specific pharmacologic GSK-3 inhibitors and siRNA knockdown of GSK-3α or GSK-3β isoforms both reduced cell motility. These data outline previously unidentified pathways and inhibitors that may be useful for the development of novel anti-invasive therapeutics for the treatment of brain tumors. PMID:18715951

  13. Differential anti-cancer effects of purified EPA and DHA and possible mechanisms involved.

    PubMed

    Serini, S; Fasano, E; Piccioni, E; Cittadini, A R M; Calviello, G

    2011-01-01

    As the concepts of pharmaconutrition are receiving increasing attention, it seems essential to clearly assess the effects of specific dietary compounds in specific groups of patients or clinical conditions. We are herein interested in better defining the differential anti-neoplastic effects of the two major n-3 long chain polyunsaturated fatty acids present in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The efficiency of these fatty acids represents a subject of intense interest and debate, and whereas plenty of preclinical studies have strongly demonstrated their preventive and therapeutic effect in different kinds of cancers, the results of the epidemiologic studies are still controversial, and only a few trials have been performed. It has been reported that EPA and DHA may act either through the same or different mechanisms, thus suggesting that a differential efficacy could exist. At present, however, this point has not been clarified, although its better comprehension would allow a more proper and effective use of these fatty acids in the human interventional studies. In an attempt to elucidate this aspect we have herein analyzed the data obtained in the studies which have directly compared the antitumor effects of separate treatments with EPA or DHA. Most of the in vitro data indicate DHA as the more powerful antineoplastic agent. However, an equivalent efficiency of EPA and DHA is suggested by the few in vivo studies. Possible reasons for this discrepancy are discussed and pathways of cell growth that could be differentially influenced by EPA and DHA are described. PMID:21824086

  14. Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.

    PubMed

    Lindahl, Anders; Sjöberg, Asa; Bredberg, Ulf; Toreson, Helena; Ungell, Anna-Lena; Lennernäs, Hans

    2004-01-01

    The first purpose of this study was to investigate the in vivo absorption, biliary secretion, and first-pass effect of fluvastatin following regional intestinal dosing in the rat. We also examined the membrane transport mechanisms and made in silico predictions of the relative importance of various intestinal regions to the human absorption of fluvastatin. Fluvastatin was administered intravenously (2, 10, and 20 micromol/kg) and into the duodenum (1.46, 2.92, 7.32, and 14.6 micromol/kg), jejunum (14.6 micromol/kg), ileum (1.46 and 14.6 mciromol/kg), and colon (1.46 and 14.6 micromol/kg) as a solution to conscious rats. In a separate group of rats, bile was collected after an i.v. dose of fluvastatin (2 micromol/kg). In the Caco-2 model the bidirectional transport of fluvastatin (16 microM) was investigated with and without various efflux inhibitors (verapamil, vinblastine, probenecid, and indomethacin, 160 microM). The human in vivo absorption of fluvastatin from an oral immediate release tablet and that from an oral extended release tablet (both 40 mg) were simulated in GastroPlus. Neither the dose nor the intestinal region influenced the bioavailability of fluvastatin significantly. The rate of absorption was, however, affected by both the dose and the site of administration; duodenum = jejunum > colon > ileum, and higher following the high dose. Increasing the i.v. dose from 2 to 20 micromol/kg decreased the clearance (26 +/- 3 to 12 +/- 1 mL/min/kg), the hepatic extraction (66 +/- 8 to 30 +/- 2%), and the volume of distribution (7.3 +/- 0.3 to 2.1 +/- 0.7 L/kg) for fluvastatin (p < 0.05). Neither bile cannulation nor bile sampling affected the pharmacokinetics. Fluvastatin was secreted into the bile, probably by active transport. The in vitro permeability for fluvastatin was high (>10 x 10(-6) cm/s). Indomethacin, but not the other inhibitors, affected the transport in both directions suggesting mrp2 to be involved. In silico, 93% of the dose was absorbed from

  15. Possible involvement of inflammatory/reparative processes in the development of uterine fibroids.

    PubMed

    Protic, Olga; Toti, Paolo; Islam, Md Soriful; Occhini, Rossella; Giannubilo, Stefano Raffaele; Catherino, William H; Cinti, Saverio; Petraglia, Felice; Ciavattini, Andrea; Castellucci, Mario; Hinz, Boris; Ciarmela, Pasquapina

    2016-05-01

    Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the "usual leiomyoma", characterized by overexpression of ECM proteins, whereas the "cellular type" has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the "usual type". Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the "usual type", we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the "cellular type", stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth. PMID:26613601

  16. Possible involvement of oxytocin in modulating the stress response in lactating dairy cows

    PubMed Central

    Sutherland, Mhairi A.; Tops, Mattie

    2014-01-01

    Oxytocin can attenuate the physiological and behavioral response to stress in animals. In this study we investigated the relationship between plasma oxytocin concentrations and the behavioral and physiological response of dairy cows to a repeated psychological stressor (novel environment). Twenty lactating multi-parous dairy cows were milked in a familiar milking parlor and in a novel environment. Blood samples were collected before and after milking in the familiar parlor (baseline) and on the second and fifth day in the novel parlor to measure plasma cortisol and oxytocin concentrations. Heart rate was recorded on all cows during milking in the familiar and novel environment. On all test days, the behavioral response of cows to milk cluster attachment was scored. On day 2 in the novel parlor, the oxytocin response, cortisol concentrations and heart rate were greater, and heart rate variability was lower than baseline values recorded in the familiar parlor. The results from this study suggest that oxytocin release is increased in response to exposure to a psychological stressor (novel environment) and that cows adapt to this stressor over time. After initial suppression, oxytocin levels increased over days of milking in a novel environment, whereas indicators of stress simultaneously decreased. Furthermore, the oxytocin increase was associated with habituation of the cortisol response in anticipation of milking in a novel environment, suggesting that oxytocin may be involved in habituation to a novel environment in dairy cows. This mechanism of habituation to novel environments may reflect an association between oxytocin and a “familiarization-habituation response” to repeated exposure to an initially novel environment that has previously been reported in humans. PMID:25228892

  17. Possible Segregated Ice at the Phoenix Landing Site: Was Liquid Water Involved?

    NASA Astrophysics Data System (ADS)

    Stoker, C.; Blaney, D.; Hecht, M.; Catling, D.; Pike, W. T.; Mellon, M.; Kounaves, S.; Lemmon, M.

    2008-12-01

    exposed in Goldilocks trench and left undisturbed for 79 sols. During this time, the brightness of the material slowly faded and, by sol 99, a sublimation lag covered the bright deposit with nearly the same spectral properties as soil. It was not possible to obtain a large enough sample of the lag to directly measure salt concentration with a wet chemistry cell. Instead, a small sample of the lag was examined with the Optical Microscope to look for morphological evidence of salts. The material was stickier and more cohesive than previous soil samples examined with the microscope, and a population of light colored particles up to 30 microns in diameter with evidence of angularity consistent with microcrystallinity was found. This observation is suggestive of possible salts more concentrated in this area. In conclusion, the microscopy results are consistent with a liquid water formation mechanism but inconclusive without a direct measurement of the composition of the material.

  18. Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

    NASA Technical Reports Server (NTRS)

    Sajdel-Sulkowska, E. M.; Li, G. H.; Ronca, A. E.; Baer, L. A.; Sulkowski, G. M.; Koibuchi, N.; Wade, C. E.

    2001-01-01

    The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

  19. High fat diet alters lactation outcomes: possible involvement of inflammatory and serotonergic pathways.

    PubMed

    Hernandez, Laura L; Grayson, Bernadette E; Yadav, Ekta; Seeley, Randy J; Horseman, Nelson D

    2012-01-01

    Delay in the onset of lactogenesis has been shown to occur in women who are obese, however the mechanism altered within the mammary gland causing the delay remains unknown. Consumption of high fat diets (HFD) has been previously determined to result decreased litters and litter numbers in rodent models due to a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from fat) diet versus a low-fat diet (LFD; 10% kcal from fat) to female Wistar rats on lactation outcomes. Feeding of HFD diet resulted in increased pup weights compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed in mothers on HFD but they began to produce copious milk volumes beginning 2 d post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected from lactating animals on HFD diet, displayed a disrupted morphologies, with very few and small alveoli. Consistently, there was a significant decrease in the mRNA expression of milk protein genes, glucose transporter 1 (GLUT1) and keratin 5 (K5), a luminobasal cell marker in the mammary glands of HFD lactating animals. Expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and the 5-HT(7) receptor (HTR7), which regulates mammary gland involution, were significantly increased in mammary glands of HFD animals. Additionally, we saw elevation of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). These results indicate that consumption of HFD impairs mammary parenchymal tissue and impedes its ability to synthesize and secrete milk, possibly through an increase in 5-HT production within the mammary gland leading to an inflammatory process. PMID:22403677

  20. Inhibition of hormone-stimulated lipolysis by clofibrate. A possible mechanism for its hypolipidemic action.

    PubMed Central

    D'Costa, M A; Angel, A

    1975-01-01

    The present study was undertaken to investigate the mechanism of the antilipolytic action of clofibrate (p-chlorophenoxyisobutyrate). Clofibrate, in the dose range of 10-80 mg/199 ml, inhibited the initial rate of norepinephrine-stimulated lipolysis 17-44 percent in isolated rat fat cells. At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat. Inhibition of lipolysis by clofibrate occurred at all concentrations of norepinephrine and ACTH (0.02-0.1 mug/ml) but did not occur with equilipolytic concentrations of dibutyryl cyclic AMP, suggesting a proximal site of action on the lipolytic sequence. Clofibrate reduced by 60 percent (315plus or minus40 vs. 120plus or minus25 pmol/g lipid; meanplus or minusSEM) the norepinephrine-stimulated initial rise in cyclic AMP, measured 10 min after addition of hormone. Because the antilipolytic effect occurred in the presence of glucose and without altering cellular ATP levels, the reduction in intracellular cyclic AMP levels could not be attributed to uncoupling of oxidative metabolism or to secondary effects of free fatty acid accumulation. In the secondary effects of free fatty acid accumulation. In the presence of procaine-HC1, which blocks hormone-stimulated lipolysis without inhibiting cyclic AMP accumulation, addition of clofibrate prevented the hormone-stimulated rise in cyclic AMP. Clofibrate did not affect the activity of the low-Km 3',5'-cyclic AMP phosphodiesterase in norepinephrine-stimulated adipocytes. These data suggest that the antilipolytic effect of clofibrate is due to its suppression of cyclic AMP production by inhibition of adenylate cyclase. The drug's hypolipidemic action may in part be explained by its antilipolytic effect, which deprives the liver of free fatty acid substrate for lipoprotein synthesis. Images PMID:162783

  1. Sexual plasticity in fish: a possible target of endocrine disruptor action.

    PubMed

    Nagahama, Yoshitaka; Nakamura, Masaru; Kitano, Takeshi; Tokumoto, Toshinobu

    2004-01-01

    Various genetic and molecular approaches have been used to investigate the mechanisms of sex determination, gonadal sex differentiation, and sex change in fish. We identified, for the first time in nonmammalian vertebrates, DMY, as the sex-determining gene of medaka. In tilapia, endogenous estrogens act as the natural inducers of ovarian differentiation, while DMRT1 may be important for testicular differentiation. In the protogynous wrasse, a rapid decline in serum estradiol-17beta levels may be an initial trigger of the female-to-male sex change. Both sex steroids and endocrine disrupters do not seem to act at the level of the sex-determining gene, but during gonadal sex differentiation. The Japanese flounder exhibits temperature-dependent sex determination. Some of the estrogenic endocrine disrupters induce feminization of the flounder larvae reared at the masculinizing temperature. The actions of these sex steroids and endocrine disrupters may be mediated by the actions of somatic cells within gonads. Thus, sexual plasticity of gonads during sex differentiation may be implicated through the somatic cells within gonads. Cloning and sequencing of a number of genes that are considered to be associated with gonadal sex differentiation have been performed and some are still in progress. These molecular probes provide useful tools for understanding not only the molecular mechanisms of sex determination and gonadal sex differentiation but also provide important basic information for studying the effects of endocrine-disrupting chemicals during these periods. PMID:15746890

  2. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

    PubMed Central

    Griffin, Michael O.; Ceballos, Guillermo; Villarreal, Francisco

    2010-01-01

    Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects. PMID:20951211

  3. Antifungal activity of salicylic acid against Penicillium expansum and its possible mechanisms of action.

    PubMed

    da Rocha Neto, Argus Cezar; Maraschin, Marcelo; Di Piero, Robson Marcelo

    2015-12-23

    Apple is a fruit widely produced and consumed around the world. Blue mold (Penicillium expansum) is one of the main postharvest diseases in apples, leading to a wide use of fungicides and the search for alternative products. The aim of this study was to assess the effect of salicylic acid (SA) against P. expansum, elucidating its mechanisms of action. The antimicrobial effect was determined by exposing conidia to a 2.5 mM SA solution for 0 to 120 min, followed by incubation. The effect of pH on the efficacy of SA against P. expansum was assessed both in vitro and in situ. The action mechanisms were investigated through fluorescence assays, measurement of protein leakage, lipid damage, and transmission electronic microscopy. SA was capable of inhibiting 90% of the fungal germination after 30 min, causing damage to the conidial plasma membrane and leading to protein leakage up to 3.2 μg of soluble protein per g of mycelium. The pH of the SA solution affected the antimicrobial activity of this secondary metabolite, which inhibited the germination of P. expansum and the blue mold incidence in apples in solutions with pH≤3 by 100%, gradually losing its activity at higher pH. PMID:26340673

  4. Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models.

    PubMed

    Esposito, Emilio Xavier; Hopfinger, Anton J; Shao, Chi-Yu; Su, Bo-Han; Chen, Sing-Zuo; Tseng, Yufeng Jane

    2015-10-01

    Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted from the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints. PMID:26200234

  5. Model-based action planning involves cortico-cerebellar and basal ganglia networks.

    PubMed

    Fermin, Alan S R; Yoshida, Takehiko; Yoshimoto, Junichiro; Ito, Makoto; Tanaka, Saori C; Doya, Kenji

    2016-01-01

    Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions, and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum, and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen, and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy. PMID:27539554

  6. Model-based action planning involves cortico-cerebellar and basal ganglia networks

    PubMed Central

    Fermin, Alan S. R.; Yoshida, Takehiko; Yoshimoto, Junichiro; Ito, Makoto; Tanaka, Saori C.; Doya, Kenji

    2016-01-01

    Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions, and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum, and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen, and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy. PMID:27539554

  7. 31 CFR 363.45 - What are the rules for judicial and administrative actions involving securities held in...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... savings bond, or the registered owner of an undelivered gift security held in TreasuryDirect. ... administrative actions involving securities held in TreasuryDirect ®? 363.45 Section 363.45 Money and Finance... Governing Securities Held in TreasuryDirect § 363.45 What are the rules for judicial and...

  8. 24 CFR 248.221 - Approval of a plan of action that involves termination of low income affordability restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... involves termination of low income affordability restrictions. 248.221 Section 248.221 Housing and Urban... LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES PREPAYMENT OF LOW INCOME HOUSING MORTGAGES Prepayment and Plans of Action Under the Emergency Low Income Preservation Act of...

  9. Investigating the Possibilities of Creating a Community of Practice. Action Research in Three Educational Institutions

    ERIC Educational Resources Information Center

    Flogaitis, Evgenia; Nomikou, Christina; Naoum, Elli; Katsenou, Christina

    2012-01-01

    The educational approach views the community of practice as a community of teachers and students who share common rules and values, information and experiences through dialogue and collaboration. Three doctoral theses are in progress at the University of Athens which study the possibilities of creating a community of practice in three different…

  10. Association of warfarin dose with genes involved in its action and metabolism

    PubMed Central

    Wadelius, Mia; Chen, Leslie Y.; Eriksson, Niclas; Bumpstead, Suzannah; Ghori, Jilur; Wadelius, Claes; Bentley, David; McGinnis, Ralph

    2006-01-01

    We report an extensive study of variability in genes encoding proteins that are believed to be involved in the action and biotransformation of warfarin. Warfarin is a commonly prescribed anticoagulant that is difficult to use because of the wide interindividual variation in dose requirements, the narrow therapeutic range and the risk of serious bleeding. We genotyped 201 patients for polymorphisms in 29 genes in the warfarin interactive pathways and tested them for association with dose requirement. In our study, polymorphisms in or flanking the genes VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, APOE, EPHX1, CALU, GGCX and ORM1-ORM2 and haplotypes of VKORC1, CYP2C9, CYP2C8, CYP2C19, PROC, F7, GGCX, PROZ, F9, NR1I2 and ORM1-ORM2 were associated with dose (P < 0.05). VKORC1, CYP2C9, CYP2C18 and CYP2C19 were significant after experiment-wise correction for multiple testing (P < 0.000175), however, the association of CYP2C18 and CYP2C19 was fully explained by linkage disequilibrium with CYP2C9*2 and/or *3. PROC and APOE were both significantly associated with dose after correction within each gene. A multiple regression model with VKORC1, CYP2C9, PROC and the non-genetic predictors age, bodyweight, drug interactions and indication for treatment jointly accounted for 62% of variance in warfarin dose. Weaker associations observed for other genes could explain up to ∼10% additional dose variance, but require testing and validation in an independent and larger data set. Translation of this knowledge into clinical guidelines for warfarin prescription will be likely to have a major impact on the safety and efficacy of warfarin. Electronic supplementary material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00439-006-0260-8 and is accessible for authorized users. PMID:17048007

  11. Carbonic anhydrase and urease: an investigation in vitro on the possibility of a synergic action.

    PubMed

    Botré, C; Botré, F

    1989-07-27

    The indirect interactions between the carbonic anhydrase (CA) and urease (UR) are investigated in the present work using rate determinations detected by combined potentiometric measurements. It is shown that, in accord with the mass-action law for the two enzyme catalyzed reactions, the two enzymes assume a synergic pattern: the increase in the rate of removal of CO2 from the solution facilitated by CA increases the rate of production of NH3 consequent from urea dissociation. The experimental system which has been set up to monitor these interactions consists of a potentiometric apparatus to follow the gaseous exchanges of CO2 and NH3 which take place from a buffered solution containing both CA and UR. The results of the present work are consistent with, and add a further support to the finding of Dodgson and Forster, who first demonstrated in vivo the existence of an indirect linkage between urea production and CA catalytic activity. PMID:2502184

  12. Root-Shoot Signaling crosstalk involved in the shoot growth promoting action of rhizospheric humic acids

    PubMed Central

    Olaetxea, Maite; Mora, Verónica; García, Andrés Calderin; Santos, Leandro Azevedo; Baigorri, Roberto; Fuentes, Marta; Garnica, María; Berbara, Ricardo Luis Louro; Zamarreño, Angel Maria; Garcia-Mina, Jose M.

    2016-01-01

    ABSTRACT Numerous studies have shown the ability of humic substances to improve plant development. This action is normally reflected in an enhancement of crop yields and quality. However, the mechanisms responsible for this action of humic substances remain rather unknown. Our studies have shown that the shoot promoting action of sedimentary humic acids is dependent of its ability to increase root hydraulic conductivity through signaling pathways related to ABA, which in turn is affected in roots by humic acids in an IAA-NO dependent way. Furthermore, these studies also indicate that the primary action of humic acids in roots might also be physical, resulting from a transient mild stress caused by humic acids associated with a fouling-cleaning cycle of wall cell pores. Finally the role of alternative signal molecules, such as ROS, and corresponding signaling pathways are also discussed and modeled in the context of the above-mentioned framework. PMID:26966789

  13. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    SciTech Connect

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

    2015-05-15

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

  14. Possibilities for achieving x-ray lasing action by use of high-order multiphoton processes. [lambda = 10 nm

    SciTech Connect

    Clark, C.W.; Littman, M.G.; McIlrath, T.J.; Miles, R.; Skinner, C.H.; Suckewer, S.; Valeo, E.

    1985-12-01

    We consider some possible mechanisms for producing gain in the 10 nm spectral region. They involve the creation of a population inversion in a confined plasma column by selective excitation of multicharged ions via absorption of many (>10) ultraviolet photons. Specific treatment is made of Kr-like ions pumped by a KrF excimer laser. 27 refs., 5 figs.

  15. Prolactin as a modulator of lymphocyte responsiveness provides a possible mechanism of action for cyclosporine.

    PubMed Central

    Hiestand, P C; Mekler, P; Nordmann, R; Grieder, A; Permmongkol, C

    1986-01-01

    Lymphocyte responsiveness in rats was found to depend on serum prolactin levels. Blocking pituitary prolactin release with bromocriptine severely reduces lymphocyte reactivity in vitro (mixed lymphocyte reaction) as well as in vivo (graft-versus-host reaction). In addition, evidence for a prolactin/growth hormone-related mRNA species produced in mitogen- and antigen-stimulated lymphocytes has been obtained. Prolactin was shown to compete in a dose-dependent fashion with the immunosuppressant cyclosporine (cyclosporin A) for a common binding site on the surface of T lymphocytes. Further, stimulation of prolactin secretion reversed the immunosuppression induced by cyclosporine. We conclude that prolactin is involved in the maintenance of T-cell immunocompetence and that the immunosuppressive effects of cyclosporine may be mediated by the displacement of prolactin from binding sites on lymphocytes. Images PMID:2939454

  16. Elucidation of possible mechanism of analgesic action of Valeriana wallichii DC chemotype (patchouli alcohol) in experimental animal models.

    PubMed

    Sah, Sangeeta Pilkhwal; Mathela, Chandra S; Chopra, Kanwaljit

    2010-03-01

    Valeriana wallichii (Family Valerianaceae), popularly named as Indian valerian, exists as three chemotypes. Aim of the study was to evaluate the effect of V. wallichii chemotype (patchouli alcohol) extract (DCME) and essential oil (VPAEO) on experimental models of nociception and to elucidate its possible mechanism of action. Analgesic effect was evaluated using acetic acid induced writhing and tail flick model. DCME and VPAEO (40 and 80 mg/kg, p.o.) significantly inhibited the number of writhings as compared to vehicle treated group. None of the doses of DCME and VPAEO exhibited any effect in tail flick model suggesting only peripheral analgesic activity. When studied for mechanism of action in acetic acid induced writhing, subeffective dose of essential oil significantly potentiated the effect of aspirin while no potentiation was seen in case of extract. These data suggest that essential oil VPAEO exerted peripheral analgesic via inhibition of prostaglandin synthesis. PMID:21046983

  17. Taking Action: An Educator's Guide to Involving Students in Environmental Projects

    ERIC Educational Resources Information Center

    Council for Environmental Education, 2012

    2012-01-01

    Developed in cooperation with the World Wildlife Fund, "Taking Action" inspires ideas and provides models for conducting effective environmental projects--projects that dynamically engage students from start to finish. From adopting species to protecting habitats to saving energy and creating publications, this guide will help educators plan,…

  18. What Will Teachers Do to Involve Parents in Education?: Using a Theory of Reasoned Action

    ERIC Educational Resources Information Center

    Pryor, Brandt W.; Pryor, Caroline R.

    2009-01-01

    Parents' involvement in their children's education is associated with a variety of benefits, including higher achievement, yet teachers are not uniformly supportive and encouraging. Teacher attitudes and beliefs about parental involvement are a predictive factor which schools, and preservice programs, could influence, yet little is known about how…

  19. Antimicrobial Activity and Possible Mechanism of Action of Citral against Cronobacter sakazakii

    PubMed Central

    Shi, Chao; Song, Kaikuo; Zhang, Xiaorong; Sun, Yi; Sui, Yue; Chen, Yifei; Jia, Zhenyu; Sun, Huihui; Sun, Zheng; Xia, Xiaodong

    2016-01-01

    Citral is a flavor component that is commonly used in food, beverage and fragrance industries. Cronobacter sakazakii is a food-borne pathogen associated with severe illness and high mortality in neonates and infants. The objective of the present study was to evaluate antimicrobial effect of citral against C. sakazakii strains. The minimum inhibitory concentration (MIC) of citral against C. sakazakii was determined via agar dilution method, then Gompertz models were used to quantitate the effect of citral on microbial growth kinetics. Changes in intracellular pH (pHin), membrane potential, intracellular ATP concentration, and membrane integrity were measured to elucidate the possible antimicrobial mechanism. Cell morphology changes were also examined using a field emission scanning electron microscope. The MICs of citral against C. sakazakii strains ranged from 0.27 to 0.54 mg/mL, and citral resulted in a longer lag phase and lower growth rate of C. sakazakii compared to the control. Citral affected the cell membrane of C. sakazakii, as evidenced by decreased intracellular ATP concentration, reduced pHin, and cell membrane hyperpolarization. Scanning electron microscopy analysis further confirmed that C. sakazakii cell membranes were damaged by citral. These findings suggest that citral exhibits antimicrobial effect against C. sakazakii strains and could be potentially used to control C. sakazakii in foods. However, how it works in food systems where many other components may interfere with its efficacy should be tested in future research before its real application. PMID:27415761

  20. Antimicrobial Activity and Possible Mechanism of Action of Citral against Cronobacter sakazakii.

    PubMed

    Shi, Chao; Song, Kaikuo; Zhang, Xiaorong; Sun, Yi; Sui, Yue; Chen, Yifei; Jia, Zhenyu; Sun, Huihui; Sun, Zheng; Xia, Xiaodong

    2016-01-01

    Citral is a flavor component that is commonly used in food, beverage and fragrance industries. Cronobacter sakazakii is a food-borne pathogen associated with severe illness and high mortality in neonates and infants. The objective of the present study was to evaluate antimicrobial effect of citral against C. sakazakii strains. The minimum inhibitory concentration (MIC) of citral against C. sakazakii was determined via agar dilution method, then Gompertz models were used to quantitate the effect of citral on microbial growth kinetics. Changes in intracellular pH (pHin), membrane potential, intracellular ATP concentration, and membrane integrity were measured to elucidate the possible antimicrobial mechanism. Cell morphology changes were also examined using a field emission scanning electron microscope. The MICs of citral against C. sakazakii strains ranged from 0.27 to 0.54 mg/mL, and citral resulted in a longer lag phase and lower growth rate of C. sakazakii compared to the control. Citral affected the cell membrane of C. sakazakii, as evidenced by decreased intracellular ATP concentration, reduced pHin, and cell membrane hyperpolarization. Scanning electron microscopy analysis further confirmed that C. sakazakii cell membranes were damaged by citral. These findings suggest that citral exhibits antimicrobial effect against C. sakazakii strains and could be potentially used to control C. sakazakii in foods. However, how it works in food systems where many other components may interfere with its efficacy should be tested in future research before its real application. PMID:27415761

  1. Rat epileptic seizures evoked by BmK {alpha}IV and its possible mechanisms involved in sodium channels

    SciTech Connect

    Chai Zhifang; Bai Zhantao; Zhang Xuying; Liu Tong; Pang Xueyan; Ji Yonghua . E-mail: yhji@server.shcnc.ac.cn

    2007-05-01

    This study showed that rat unilateral intracerebroventricular injection of BmK {alpha}IV, a sodium channel modulator derived from scorpion Buthus martensi Karsch, induced clusters of spikes, epileptic discharges and convulsion-related behavioral changes. BmK {alpha}IV potently promoted the release of endogenous glutamate from rat cerebrocortical synaptosomes. In vitro examination of the effect of BmK {alpha}IV on intrasynaptosomal free calcium concentration [Ca{sup 2+}]{sub i} and sodium concentration [Na{sup +}]{sub i} revealed that BmK {alpha}IV-evoked glutamate release from synaptosomes was associated with an increase in Ca{sup 2+} and Na{sup +} influx. Moreover, BmK {alpha}IV-mediated glutamate release and ion influx was completely blocked by tetrodotoxin, a blocker of sodium channel. Together, these results suggest that the induction of BmK {alpha}IV-evoked epileptic seizures may be involved in the modulation of BmK {alpha}IV on tetrodotoxin-sensitive sodium channels located on the nerve terminal, which subsequently enhances the Ca{sup 2+} influx to cause an increase of glutamate release. These findings may provide some insight regarding the mechanism of neuronal action of BmK {alpha}IV in the central nervous system for understanding epileptogenesis involved in sodium channels.

  2. Anger fosters action. Fast responses in a motor task involving approach movements toward angry faces and bodies.

    PubMed

    de Valk, Josje M; Wijnen, Jasper G; Kret, Mariska E

    2015-01-01

    Efficiently responding to others' emotions, especially threatening expressions such as anger and fear, can have great survival value. Previous research has shown that humans have a bias toward threatening stimuli. Most of these studies focused on facial expressions, yet emotions are expressed by the whole body, and not just by the face. Body language contains a direct action component, and activates action preparation areas in the brain more than facial expressions. Hence, biases toward threat may be larger following threatening bodily expressions as compared to facial expressions. The current study investigated reaction times of movements directed toward emotional bodies and faces. For this purpose, a new task was developed where participants were standing in front of a computer screen on which angry, fearful, and neutral faces and bodies were presented which they had to touch as quickly as possible. Results show that participants responded faster to angry than to neutral stimuli, regardless of the source (face or body). No significant difference was observed between fearful and neutral stimuli, demonstrating that the threat bias was not related to the negativity of the stimulus, but likely to the directness of the threat in relation to the observer. Whereas fearful stimuli might signal an environmental threat that requires further exploration before action, angry expressions signal a direct threat to the observer, asking for immediate action. This study provides a novel and implicit method to directly test the speed of actions toward emotions from the whole body. PMID:26388793

  3. Constitutional Law--State Action--A Lesser Standard of State Action Is to Be Employed for Claims Involving Sex Discrimination. Weise v. Syracuse University (2d Cir. 1975)

    ERIC Educational Resources Information Center

    Ronan, James Michael

    1976-01-01

    The impact of Weise v. Syracuse University, involving alleged sex discrimination in university hiring practices, is unclear but the appeals court held that a less stringent state action standard should be employed in claims involving sex discrimination. (LBH)

  4. Action on AMD. Optimising patient management: act now to ensure current and continual delivery of best possible patient care

    PubMed Central

    Amoaku, W; Blakeney, S; Freeman, M; Gale, R; Johnston, R; Kelly, S P; McLaughlan, B; Sahu, D; Varma, D

    2012-01-01

    In recent years, there have been significant advances in the clinical management of patients with wet age-related macular degeneration (wet AMD)—a rapidly progressing and potentially blinding degenerative eye disease. Wet AMD is responsible for more than half of registered severe sight impairment (blindness) in the United Kingdom, and patients who are being treated for wet AMD require frequent and long-term follow-up for treatment to be most effective. The clinical workload associated with the frequent follow-up required is substantial. Furthermore, as more new patients are diagnosed and the population continues to age, the patient population will continue to increase. It is thus vital that clinical services continue to adapt so that they can provide a fast and efficient service for patients with wet AMD. This Action on AMDdocument has been developed by eye health-care professionals and patient representatives, the Action on AMDgroup. It is intended to highlight the urgent and continuing need for change within wet AMD services. This document also serves as a guide for eye health-care professionals, NHS commissioners, and providers to present possible solutions for improving NHS retinal and macular services. Examples of good practice and service development are considered and can be drawn upon to help services meet the recommended quality of care and achieve best possible outcomes. PMID:22302094

  5. Baking together-the coordination of actions in activities involving people with dementia.

    PubMed

    Majlesi, Ali Reza; Ekström, Anna

    2016-08-01

    This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways. PMID:27531451

  6. Involvement of PPARγ in the antitumoral action of cannabinoids on hepatocellular carcinoma.

    PubMed

    Vara, D; Morell, C; Rodríguez-Henche, N; Diaz-Laviada, I

    2013-01-01

    Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Both cannabinoids increased the activity and intracellular level of PPARγ mRNA and protein, which was abolished by the PPARγ inhibitor GW9662. Moreover, genetic ablation with small interfering RNA (siRNA), as well as pharmacological inhibition of PPARγ decreased the cannabinoid-induced cell death and apoptosis. Likewise, GW9662 totally blocked the antitumoral action of cannabinoids in xenograft-induced HCC tumors in mice. In addition, PPARγ knockdown with siRNA caused accumulation of the autophagy markers LC3-II and p62, suggesting that PPARγ is necessary for the autophagy flux promoted by cannabinoids. Interestingly, downregulation of the endoplasmic reticulum stress-related protein tribbles homolog 3 (TRIB3) markedly reduced PPARγ expression and induced p62 accumulation, which was counteracted by overexpression of PPARγ in TRIB3-knocked down cells. Taken together, we demonstrate for the first time that the antiproliferative action of the cannabinoids THC and JWH-015 on HCC, in vitro and in vivo, are modulated by upregulation of PPARγ-dependent pathways. PMID:23640460

  7. Student Involvement in Learning Action Packet. Research, Strategies and Programs for Special Populations.

    ERIC Educational Resources Information Center

    Research for Better Schools, Inc., Philadelphia, PA.

    To improve the responsiveness of educational programs to the needs of low achieving, at risk students, Research for Better Schools (RBS) has developed an assessment procedure. This document is the portion of that procedure that addresses the involvement of students in their learning, or how low achieving students cognitively operate on content.…

  8. Participation As Relational Process: Unpacking Involvement in Social Action and Community Service

    ERIC Educational Resources Information Center

    Jones, Jeffrey N.; Bench, Joshua H.; Warnaar, Bethany L.; Stroup, John T.

    2013-01-01

    Educators, policymakers, and other concerned adults share an interest in promoting lifelong patterns of community service in youth. Practitioners and researchers alike highlight the importance of youth participation in afterschool service activities so the author's focus in this paper is on youth involved in PeaceJam, an innovative service…

  9. Testing the Waters: Can You Involve Community Action in Your College Curriculum?

    ERIC Educational Resources Information Center

    Knapp, Elizabeth P.; Harbor, David J.; Ginwalla, Zenobia F.

    2003-01-01

    Discusses the Maury River Alliance (MRA), a cooperative program developed at the Washington and Lee University that involved local colleges, high schools, government agencies, and conservation groups. Addresses the connection between land use and water quality with a creative merging of technical, social, and educational aspects of local watershed…

  10. 77 FR 54584 - Final Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... in the Federal Register (74 FR 9411) to revise the NIH Guidelines in two regards. The first was to..., NIH/OBA revised the proposal and published a notice for comment on April 22, 2010 (75 FR 21008...-1, Experiments Involving the Cloning of Toxin Molecules with LD50 of Less Than 100 Nanograms...

  11. Estrogen involvement in social behavior in rodents: Rapid and long-term actions.

    PubMed

    Ervin, Kelsy S J; Lymer, Jennifer M; Matta, Richard; Clipperton-Allen, Amy E; Kavaliers, Martin; Choleris, Elena

    2015-08-01

    This article is part of a Special Issue ("Estradiol and cognition"). Estrogens have repeatedly been shown to influence a wide array of social behaviors, which in rodents are predominantly olfactory-mediated. Estrogens are involved in social behavior at multiple levels of processing, from the detection and integration of socially relevant olfactory information to more complex social behaviors, including social preferences, aggression and dominance, and learning and memory for social stimuli (e.g. social recognition and social learning). Three estrogen receptors (ERs), ERα, ERβ, and the G protein-coupled ER 1 (GPER1), differently affect these behaviors. Social recognition, territorial aggression, and sexual preferences and mate choice, all requiring the integration of socially related olfactory information, seem to primarily involve ERα, with ERβ playing a lesser, modulatory role. In contrast, social learning consistently responds differently to estrogen manipulations than other social behaviors. This suggests differential ER involvement in brain regions important for specific social behaviors, such as the ventromedial and medial preoptic nuclei of the hypothalamus in social preferences and aggression, the medial amygdala and hippocampus in social recognition, and the prefrontal cortex and hippocampus in social learning. While the long-term effects of ERα and ERβ on social behavior have been extensively investigated, our knowledge of the rapid, non-genomic, effects of estrogens is more limited and suggests that they may mediate some social behaviors (e.g. social learning) differently from long-term effects. Further research is required to compare ER involvement in regulating social behavior in male and female animals, and to further elucidate the roles of the more recently described G protein-coupled ERs, both the GPER1 and the Gq-mER. PMID:26122289

  12. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    PubMed Central

    Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

    2014-01-01

    Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies. PMID:24860820

  13. Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways.

    PubMed

    Bitiktaş, Soner; Kandemir, Başak; Tan, Burak; Kavraal, Şehrazat; Liman, Narin; Dursun, Nurcan; Dönmez-Altuntaş, Hamiyet; Aksan-Kurnaz, Işil; Suer, Cem

    2016-08-01

    Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK. PMID:27258653

  14. Auxin Biosynthesis, Accumulation, Action and Transport are Involved in Stress-Induced Microspore Embryogenesis Initiation and Progression in Brassica napus.

    PubMed

    Rodríguez-Sanz, Héctor; Solís, María-Teresa; López, María-Fernanda; Gómez-Cadenas, Aurelio; Risueño, María C; Testillano, Pilar S

    2015-07-01

    Isolated microspores are reprogrammed in vitro by stress, becoming totipotent cells and producing embryos and plants via a process known as microspore embryogenesis. Despite the abundance of data on auxin involvement in plant development and embryogenesis, no data are available regarding the dynamics of auxin concentration, cellular localization and the expression of biosynthesis genes during microspore embryogenesis. This work involved the analysis of auxin concentration and cellular accumulation; expression of TAA1 and NIT2 encoding enzymes of two auxin biosynthetic pathways; expression of the PIN1-like efflux carrier; and the effects of inhibition of auxin transport and action by N-1-naphthylphthalamic acid (NPA) and α-(p-chlorophenoxy) isobutyric acid (PCIB) during Brassica napus microspore embryogenesis. The results indicated de novo auxin synthesis after stress-induced microspore reprogramming and embryogenesis initiation, accompanying the first cell divisions. The progressive increase of auxin concentration during progression of embryogenesis correlated with the expression patterns of TAA1 and NIT2 genes of auxin biosynthetic pathways. Auxin was evenly distributed in early embryos, whereas in heart/torpedo embryos auxin was accumulated in apical and basal embryo regions. Auxin efflux carrier PIN1-like gene expression was induced in early multicellular embryos and increased at the globular/torpedo embryo stages. Inhibition of polar auxin transport (PAT) and action, by NPA and PCIB, impaired embryo development, indicating that PAT and auxin action are required for microspore embryo progression. NPA also modified auxin embryo accumulation patterns. These findings indicate that endogenous auxin biosynthesis, action and polar transport are required in stress-induced microspore reprogramming, embryogenesis initiation and progression. PMID:25907568

  15. On possibility of high-power terahertz emission from target under the action of powerful laser pulses

    NASA Astrophysics Data System (ADS)

    Didenko, A. N.; Rashchikov, V. I.; Fortov, V. E.

    2011-03-01

    The possibility of terahertz (THz) emission from a target irradiated by short (˜0.1 ns) high-intensity ( I ˜ 1018-1019 W/cm2) laser pulses has been studied by numerical simulations using a relativistic electromagnetic PIC code. The laser pulse action on the target generates plasma and the runaway electrons form a virtual cathode, which oscillates in the intrinsic field of electrons and the field of plasma ions. These oscillations account for the emission of radiation in a THz range. The generation efficiency is about three times as high as that in the absence of ions (according to the conventional reditron mechanism). Explanation of the observed phenomena is proposed.

  16. A review of the benefits of Satureja species on metabolic syndrome and their possible mechanisms of action.

    PubMed

    Babajafari, Siavash; Nikaein, Farzad; Mazloomi, Seyed Mohammad; Zibaeenejad, Mohammad Javad; Zargaran, Arman

    2015-07-01

    Metabolic syndrome, also known as insulin resistance disorder, is the simultaneous manifestation of multiple metabolic disorders in an individual. The present-day complementary and alternative therapies suggest several medicinal herbs that may have the potential to improve one or multiple complications of metabolic syndrome. All of them have their own limitations in efficacy and unwanted effects. Therefore, we reviewed species of Satureja as widespread medicinal herbs and potentially good remedies for metabolic syndrome. We reviewed literature found in PubMed and the ISI Web of Knowledge with the key word Satureja in the title. The influence of any species of Satureja on any disease or syndrome, enzymatic, metabolic, or physiological pathways, in human, animals, or in vitro conditions related to any characteristics of metabolic syndrome were considered. The main outcomes of treatment with Satureja species were categorized, and the possible mechanisms of action are discussed in this article. PMID:25563729

  17. Photosynthesis involvement in the mechanism of action of diphenyl ether herbicides.

    PubMed

    Ensminger, M P; Hess, F D

    1985-05-01

    Photosynthesis is not required for the toxicity of diphenyl ether herbicides, nor are chloroplast thylakoids the primary site of diphenyl ether herbicide activity. Isolated spinach (Spinacia oleracea L.) chloroplast fragments produced malonyl dialdehyde, indicating lipid peroxidation, when paraquat (1,1'-dimethyl-4,4'-bipyridinium ion) or diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] were added to the medium, but no malonyl dialdehyde was produced when chloroplast fragments were treated with the methyl ester of acifluorfen (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid), oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene], or MC15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). In most cases the toxicity of acifluorfen-methyl, oxyfluorfen, or MC15608 to the unicellular green alga Chlamydomonas eugametos (Moewus) did not decrease after simultaneous treatment with diuron. However, diuron significantly reduced cell death after paraquat treatment at all but the highest paraquat concentration tested (0.1 millimolar). These data indicate electron transport of photosynthesis is not serving the same function for diphenyl ether herbicides as for paraquat. Additional evidence for differential action of paraquat was obtained from the superoxide scavenger copper penicillamine (copper complex of 2-amino-3-mercapto-3-methylbutanoic acid). Copper penicillamine eliminated paraquat toxicity in cucumber (Cucumis sativus L.) cotyledons but did not reduce diphenyl ether herbicide toxicity. PMID:16664206

  18. Photosynthesis Involvement in the Mechanism of Action of Diphenyl Ether Herbicides 1

    PubMed Central

    Ensminger, Michael P.; Hess, F. Dan

    1985-01-01

    Photosynthesis is not required for the toxicity of diphenyl ether herbicides, nor are chloroplast thylakoids the primary site of diphenyl ether herbicide activity. Isolated spinach (Spinacia oleracea L.) chloroplast fragments produced malonyl dialdehyde, indicating lipid peroxidation, when paraquat (1,1′-dimethyl-4,4′-bipyridinium ion) or diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] were added to the medium, but no malonyl dialdehyde was produced when chloroplast fragments were treated with the methyl ester of acifluorfen (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid), oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene], or MC15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). In most cases the toxicity of acifluorfen-methyl, oxyfluorfen, or MC15608 to the unicellular green alga Chlamydomonas eugametos (Moewus) did not decrease after simultaneous treatment with diuron. However, diuron significantly reduced cell death after paraquat treatment at all but the highest paraquat concentration tested (0.1 millimolar). These data indicate electron transport of photosynthesis is not serving the same function for diphenyl ether herbicides as for paraquat. Additional evidence for differential action of paraquat was obtained from the superoxide scavenger copper penicillamine (copper complex of 2-amino-3-mercapto-3-methylbutanoic acid). Copper penicillamine eliminated paraquat toxicity in cucumber (Cucumis sativus L.) cotyledons but did not reduce diphenyl ether herbicide toxicity. PMID:16664206

  19. Central estrogen action sites involved in prepubertal restraint of pulsatile luteinizing hormone release in female rats

    PubMed Central

    UENOYAMA, Yoshihisa; TANAKA, Akira; TAKASE, Kenji; YAMADA, Shunji; PHENG, Vutha; INOUE, Naoko; MAEDA, Kei-ichiro; TSUKAMURA, Hiroko

    2015-01-01

    The present study aimed to determine estrogen feedback action sites to mediate prepubertal restraint of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release in female rats. Wistar-Imamichi strain rats were ovariectomized (OVX) and received a local estradiol-17β (estradiol) or cholesterol microimplant in several brain areas, such as the medial preoptic area (mPOA), paraventricular nucleus, ventromedial nucleus and arcuate nucleus (ARC), at 20 or 35 days of age. Six days after receiving the estradiol microimplant, animals were bled to detect LH pulses at 26 or 41 days of age, representing the pre- or postpubertal period, respectively. Estradiol microimplants in the mPOA or ARC, but not in other brain regions, suppressed LH pulses in prepubertal OVX rats. Apparent LH pulses were found in the postpubertal period in all animals bearing estradiol or cholesterol implants. It is unlikely that pubertal changes in responsiveness to estrogen are due to a change in estrogen receptor (ER) expression, because the number of ERα-immunoreactive cells and mRNA levels of Esr1, Esr2 and Gpr30 in the mPOA and ARC were comparable between the pre- and postpubertal periods. In addition, kisspeptin or GnRH injection overrode estradiol-dependent prepubertal LH suppression, suggesting that estrogen inhibits the kisspeptin-GnRH cascade during the prepubertal period. Thus, estrogen-responsive neurons located in the mPOA and ARC may play key roles in estrogen-dependent prepubertal restraint of GnRH/LH secretion in female rats. PMID:26004302

  20. Involvement of apurinic sites in the synergistic action of alkylating and intercalating drugs in Escherichia coli.

    PubMed

    Malvy, C; Safraoui, H; Bloch, E; Bertrand, J R

    1988-03-01

    The toxicity of the intercalating compounds 9-aminoellipticine (9AE) and isopropyl-oxazolopyridocarbazole (Ipr-OPC) were studied. The inhibitory effect of non-toxic doses of 9AE, which incises DNA at apurinic (AP) sites, or Ipr-OPC, which does not cleave DNA at AP sites, with non-toxic doses of the alkylating agent dimethylsulphate (DMS) on the growth of Escherichia coli strain AB1157, is additive. The same result has been observed with an exonuclease III mutant which has only 10% of the AP endonuclease activity. However, 9AE or Ipr-OPC display a synergistic toxic effect with a DMS concentration which allows 20% of E. coli AB1157 survival. This synergy is increased for 9AE in the AP endonuclease mutant when compared to the wild-type strain. Under identical conditions 9AE and Ipr-OPC have no synergistic effect on a mutant deficient in the enzymes which generate AP sites. Therefore AP sites are involved in the synergistic toxicity of DMS and the studied intercalating agents. However, the precise role of the interaction of intercalating agents with AP sites, either without cleavage (type 1 compounds) or with cleavage (type 2 compounds), in the observed effect remains an open question. PMID:3284541

  1. A mannose-receptor is possibly involved in the phagocytosis of Saccharomyces cerevisiae by seabream (Sparus aurata L.) leucocytes.

    PubMed

    Rodríguez, A; Esteban, M A; Meseguer, J

    2003-05-01

    In this paper the possible involvement of the mannose-receptor on the non-specific recognition and phagocytosis of heat killed yeast cells (Saccharomyces cerevisiae) by gilthead seabream (Sparus aurata L.) head-kidney leucocytes was established by studying the ability of different sugars to inhibit the uptake of the yeast cells by leucocytes. Leucocytes were preincubated for 30min with different concentrations of sugar (alpha-mannan, d-mannose, d-fucose, l-fucose, d-glucose, d-glucosamine and n-acetyl-glucosamine, all of them described as specific ligands of the vertebrate mannose-receptor) and afterwards incubated with FITC-labelled yeast cells for phagocytosis assays. The phagocytic ability (percentage of cells with one or more ingested yeast cells within the total cell population) and capacity (number of ingested yeast cells per cell) of leucocytes was analysed by flow cytometry. The results demonstrate the potential existence of a specific receptor-sugar or receptor-yeast cell binding process, which was saturable, specific and dose-dependent. More specifically, when leucocytes were preincubated with appropriate doses of d-mannose, d- or l-fucose, d-glucose or n-acetyl-glucosamine the phagocytosis of yeast cells by head-kidney leucocytes was partially blocked. Seabream leucocytes were also preincubated with chloroquine, a lysosomotropic drug which downregulates (in a nonspecific manner) the expression of mannose-receptors in mammals, before phagocytosis assays were performed. The results demonstrated that the phagocytosis of yeast was completely blocked by this substance. The overall results seem to corroborate the presence of the mannose-receptor in seabream phagocytes, which is involved in the non-specific binding and phagocytosis of yeast cells by head-kidney leucocytes. PMID:12711272

  2. Involvement of interleukin-1 in the inflammatory actions of aminobisphosphonates in mice

    PubMed Central

    Yamaguchi, Kouji; Motegi, Katsutoshi; Iwakura, Yoichiro; Endo, Yasuo

    2000-01-01

    Aminobisphosphonates (aminoBPs) are potent inhibitors of bone resorption. However, they cause undesirable inflammatory reactions, including fever, in humans. Intraperitoneal injection of aminoBPs into mice also induces inflammatory reactions, including a prolonged elevation of the activity of the histamine-forming enzyme, histidine decarboxylase (HDC). Because interleukin-1 (IL-1) is a typical pyrogen and a strong inducer of HDC, we examined whether aminoBPs induce inflammatory reactions in mice deficient in genes for both IL-1α and IL-1β (IL-1-KO mice). In control mice, aminoBPs induced an elevation of HDC activity and other inflammatory reactions (enlargement of the spleen, atrophy of the thymus, exudate in the thorax and increase in granulocytic cells in the peritoneal cavity). These responses were all weak or undetectable in IL-1-KO mice. We have previously shown that lipopolysaccharides (LPSs) from Escherichia coli and Prevotella intermedia (a prevalent gram-negative bacterium both in periodontitis and endodontal infections) are capable of inducing HDC activity in various tissues in mice. In control mice treated with an aminoBP, the LPS-induced elevations of serum IL-1 (α and β) and tissue HDC activity were both markedly augmented. However, such an augmentation of HDC activity was small or undetectable in IL-1-KO mice. These results, taken together with our previous findings (i) suggest that IL-1 is involved in the aminoBP-induced inflammatory reactions and (ii) lead us to think that under some conditions, inflammatory reactions induced by gram-negative bacteria might be augmented in patients treated with an aminoBP. In this study, we also obtained a result suggesting that IL-1-deficiency might be compensated by a second, unidentified, mechanism serving to induce HDC in response to LPS when IL-1 is lacking. PMID:10928970

  3. Involvement of HCN Channel in Muscarinic Inhibitory Action on Tonic Firing of Dorsolateral Striatal Cholinergic Interneurons

    PubMed Central

    Zhao, Zhe; Zhang, Kang; Liu, Xiaoyan; Yan, Haitao; Ma, Xiaoyun; Zhang, Shuzhuo; Zheng, Jianquan; Wang, Liyun; Wei, Xiaoli

    2016-01-01

    The striatum is the most prominent nucleus in the basal ganglia and plays an important role in motor movement regulation. The cholinergic interneurons (ChIs) in striatum are involved in the motion regulation by releasing acetylcholine (ACh) and modulating the output of striatal projection neurons. Here, we report that muscarinic ACh receptor (M receptor) agonists, ACh and Oxotremorine (OXO-M), decreased the firing frequency of ChIs by blocking the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Scopolamine (SCO), a nonselective antagonist of M receptors, abolished the inhibition. OXO-M exerted its function by activating the Gi/o cAMP signaling cascade. The single-cell reverse transcription polymerase chain reaction (scRT-PCR) revealed that all the five subtypes of M receptors and four subtypes of HCN channels were expressed on ChIs. Among them, M2 receptors and HCN2 channels were the most dominant ones and expressed in every single studied cholinergic interneuron (ChI).Our results suggest that ACh regulates not only the output of striatal projection neurons, but also the firing activity of ChIs themselves by activating presynaptic M receptors in the dorsal striatum. The activation of M2 receptors and blockage of HCN2 channels may play an important role in ACh inhibition on the excitability of ChIs. This finding adds a new G-protein coupled receptor mediated regulation on ChIs and provides a cellular mechanism for control of cholinergic activity and ACh release in the dorsal striatum. PMID:27047336

  4. Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion.

    PubMed

    Wang, Huabo; Sharma, Lokendra; Lu, Jie; Finch, Paul; Fletcher, Steven; Prochownik, Edward V

    2015-06-30

    The c-Myc (Myc) oncoprotein is deregulated in a large proportion of diverse human cancers. Considerable effort has therefore been directed at identifying pharmacologic inhibitors as potential anti-neoplastic agents. Three such groups of small molecule inhibitors have been described. The first is comprised of so-called "direct" inhibitors, which perturb Myc's ability to form productive DNA-binding heterodimers in association with its partner, Max. The second group is comprised of indirect inhibitors, which largely function by targeting the BET-domain protein BRD4 to prevent the proper formation of transcriptional complexes that assemble in response to Myc-Max DNA binding. Thirdly, synthetic lethal inhibitors cause the selective apoptosis of Myc over-expressing either by promoting mitotic catastrophe or altering Myc protein stability. We report here a common mechanism by which all Myc inhibitors, irrespective of class, lead to eventual cellular demise. This involves the depletion of ATP stores due to mitochondrial dysfunction and the eventual down-regulation of Myc protein. The accompanying metabolic de-regulation causes neutral lipid accumulation, cell cycle arrest, and an attempt to rectify the ATP deficit by up-regulating AMP-activated protein kinase (AMPK). These responses are ultimately futile due to the lack of functional Myc to support the requisite anabolic response. Finally, the effects of Myc depletion on ATP levels, cell cycle arrest, differentiation and AMPK activation can be mimicked by pharmacologic inhibition of the mitochondrial electron transport chain without affecting Myc levels. Thus, all Myc inhibitors promote a global energy collapse that appears to underlie many of their phenotypic consequences. PMID:26036281

  5. Involvement of HCN Channel in Muscarinic Inhibitory Action on Tonic Firing of Dorsolateral Striatal Cholinergic Interneurons.

    PubMed

    Zhao, Zhe; Zhang, Kang; Liu, Xiaoyan; Yan, Haitao; Ma, Xiaoyun; Zhang, Shuzhuo; Zheng, Jianquan; Wang, Liyun; Wei, Xiaoli

    2016-01-01

    The striatum is the most prominent nucleus in the basal ganglia and plays an important role in motor movement regulation. The cholinergic interneurons (ChIs) in striatum are involved in the motion regulation by releasing acetylcholine (ACh) and modulating the output of striatal projection neurons. Here, we report that muscarinic ACh receptor (M receptor) agonists, ACh and Oxotremorine (OXO-M), decreased the firing frequency of ChIs by blocking the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Scopolamine (SCO), a nonselective antagonist of M receptors, abolished the inhibition. OXO-M exerted its function by activating the Gi/o cAMP signaling cascade. The single-cell reverse transcription polymerase chain reaction (scRT-PCR) revealed that all the five subtypes of M receptors and four subtypes of HCN channels were expressed on ChIs. Among them, M2 receptors and HCN2 channels were the most dominant ones and expressed in every single studied cholinergic interneuron (ChI).Our results suggest that ACh regulates not only the output of striatal projection neurons, but also the firing activity of ChIs themselves by activating presynaptic M receptors in the dorsal striatum. The activation of M2 receptors and blockage of HCN2 channels may play an important role in ACh inhibition on the excitability of ChIs. This finding adds a new G-protein coupled receptor mediated regulation on ChIs and provides a cellular mechanism for control of cholinergic activity and ACh release in the dorsal striatum. PMID:27047336

  6. Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages

    SciTech Connect

    He, Xiao-dong; Tobo, Masayuki; Mogi, Chihiro; Nakakura, Takashi; Komachi, Mayumi; Murata, Naoya; Takano, Mutsumi; Tomura, Hideaki; Sato, Koichi; Okajima, Fumikazu

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Glucocorticoid (GC) induced the expression of proton-sensing TDAG8 in macrophages. Black-Right-Pointing-Pointer GC enhanced acidic pH-induced cAMP accumulation and inhibition of TNF-{alpha} production. Black-Right-Pointing-Pointer The enhancement of the GC-induced actions was lost by TDAG8 deficiency. Black-Right-Pointing-Pointer GC-induced anti-inflammatory actions are partly mediated by TDAG8 expression. -- Abstract: Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide-induced production of tumor necrosis factor-{alpha}, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-{alpha} production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable.

  7. Molecular and biochemical evidence for the involvement of calcium/calmodulin in auxin action

    NASA Technical Reports Server (NTRS)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    -dependent manner suggests that calcium/CaM regulate ZmSAUR1 at the post-translational level. Our data provide the first direct evidence for the involvement of calcium/CaM-mediated signaling in auxin-mediated signal transduction.

  8. Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus.

    PubMed Central

    Ito, M; Oiso, Y; Murase, T; Kondo, K; Saito, H; Chinzei, T; Racchi, M; Lively, M O

    1993-01-01

    A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals. Images PMID:8514868

  9. Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of glucocorticoid system.

    PubMed

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Choi, Seong-Soo; Suh, Hong-Won

    2013-10-01

    The possible involvement of glucocorticoid system in interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1β (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1β administration. We found that i.t. injection with IL-1β increased CRH mRNA level in the hypothalamus. The IL-1β administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1β significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1β injected i.t. in normal and D-glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. in normal and D-glucose-fed groups. Our results suggest that IL-1β administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system. PMID:23773309

  10. Involvement of KLF14 and egr-1 in the TGF-beta1 action on Leydig cell proliferation.

    PubMed

    Gonzalez, C R; Vallcaneras, S S; Calandra, R S; Gonzalez Calvar, S I

    2013-02-01

    Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that modulates cell homeostasis. In Leydig cells, TGF-β1 exerts stimulatory and inhibitory effect depending on the type I receptor involved in the signaling pathway. The aim of the present work was to study the signaling mechanisms and the intermediates involved in the action of TGF-β1 on TM3 Leydig cell proliferation in the presence or absence of progesterone. The MTT assay showed that the presence of progesterone in the culture media lead to a proliferative effect that was blocked by Ru 486, an inhibitor of progesterone receptor; and ALK-5 did not participate in this effect. TGF-β1 (1 ng/ml) increased the expression of p15 (an inhibitor of cell cycle) in TM3 Leydig cells, and this effect was blocked by progesterone (1μM). The expression of PCNA presented a higher increase in the cell cultured with TGF-β1 plus progesterone than in cells cultured only with TGF-β1. Progesterone induced the gene expression of endoglin, a cofactor of TGF-β1 receptor that leads to a stimulatory signaling pathway, despite of the absence of progesterone response element in endoglin gene. In addition, the presence of progesterone induced the gene expression of egr-1 and also KLF14, indicating that this steroid channels the signaling pathway into a non-canonical mechanism. In conclusion, these findings suggest that the proliferative action of TGF-β1 involves endoglin. This co-receptor might be induced by KLF14 which is probably activated by progesterone. PMID:23317878

  11. [Anti-inflammatory activity of benzo(c) phenanthridine derivatives and possible mechanisms of action (author's transl)].

    PubMed

    Iwata, H; Yamamoto, I; Masukawa, T; Komoriya, K; Iwaki, H

    1977-07-01

    Of five newly synthesized benzo[c]phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I. PMID:21834

  12. The mode of action of interferons in viral infections and their possible role in the control of hepatitis B.

    PubMed

    Billiau, A

    1986-01-01

    Interferons can alter the course of virus infections by inhibiting virus replication at the intracellular level and by modifying the aspecific and specific immune response to viral antigens in body fluids and on cellular surfaces. Treatment of isolated cells with interferon renders them resistant to infections by viruses belonging to virtually any family. Knowledge of the mechanism of this effect is derived from studies employing both DNA (especially vaccinia virus and SV40) and RNA-viruses (especially picorna-, toga-, rhabdo-, reo- and retroviruses). Interferon induces multiple alterations in the level and state of intracellular regulatory molecules, leading to inhibition of virus replication at several possible steps. In the case of certain DNA viruses, transcription of viral DNA seems to be inhibited. In the case of RNA viruses the target for interferon action is mainly translation. The retroviridae constitute a special case and, in view of their analogy with the hepadnaviridae, are of particular relevance to the possible effects of interferon on the replication of HBV. Interferon inhibits one or more initial stages of primary infection of cells by transforming or nontransforming retroviruses, thereby preventing or delaying the synthesis and/or integration of viral DNA. In cells that already contain an integrated and fully expressed retrovirus genome, interferon treatment results in a reduced release of viral particles as well as a downward shift of the ratios between the numbers of infectious vs noninfectious particles. Immuno-modulatory properties of interferon which might alter the course of HBV-infection include: potentiation of cytotoxic activity of lymphocytes and macrophages; direct anti-inflammatory effects; enhancement or depression in antibody formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2439572

  13. Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

    PubMed Central

    Nicastro, Humberto; da Luz, Claudia Ribeiro; Chaves, Daniela Fojo Seixas; Bechara, Luiz Roberto Grassmann; Voltarelli, Vanessa Azevedo; Rogero, Marcelo Macedo; Lancha, Antonio Herbert

    2012-01-01

    Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs), especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation. PMID:22536489

  14. Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

    PubMed

    Guo, Xueling; Shang, Jin; Deng, Yan; Yuan, Xiao; Zhu, Die; Liu, Huiguo

    2015-07-01

    Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH. PMID:25936416

  15. PPARβ/δ and γ in a rat model of Parkinson's disease: possible involvement in PD symptoms.

    PubMed

    Falcone, Roberta; Florio, Tiziana Marilena; Di Giacomo, Erica; Benedetti, Elisabetta; Cristiano, Loredana; Antonosante, Andrea; Fidoamore, Alessia; Massimi, Mara; Alecci, Marcello; Ippoliti, Rodolfo; Giordano, Antonio; Cimini, Annamaria

    2015-05-01

    Parkinson's disease is one of the most common neurologic disorder, affecting about 1-4% of persons older than 60 years. Among the proposed mechanisms of PD generation, free radical damage is believed to play a pivotal role in the development and/or progression of the disease. Recently, PPARs, a class of transcription factors involved in several pathways both in physiological and pathological conditions, have been linked by us and others to neurodegeneration. Particularly, PPARγ and its ligands have been indicated as potential therapeutic targets for the treatment of several pathological conditions associated with neuroinflammation within the CNS. The anti-inflammatory function of PPARγ has attracted attention since agonists exert a broad spectrum of protective effects in several animal models of neurological diseases, including psychiatric diseases. On the other hand a detrimental role for PPARβ/δ has been proposed in Alzheimer, being closely related to the decrease of BDNF and Trkfl. On these bases, in this work we used a 6-OHDA hemi-lesioned rat model, inducing loss of dopaminergic neurons, to study the effects of the lesion at three time points from the lesion (1, 2, and 3 weeks), in relevant areas of PD motor symptoms, such as substantia nigra and globus pallidus and in the area of reward and mood control, the nucleus accumbens. In particular, it was studied: (i) the expression of BDNF and its downstream signals; (ii) the modulation of PPARs levels. The results obtained indicate the possible use of a dual PPARβ/δ antagonist/PPARγ agonist to counteract primary and secondary signs of PD neurodegeneration. PMID:25530507

  16. Possible Involvement of Hepatitis B Virus Infection of Hepatocytes in the Attenuation of Apoptosis in Hepatic Stellate Cells

    PubMed Central

    Sasaki, Reina; Kanda, Tatsuo; Nakamura, Masato; Nakamoto, Shingo; Haga, Yuki; Wu, Shuang; Shirasawa, Hiroshi; Yokosuka, Osamu

    2016-01-01

    Background The induction of apoptosis in hepatic stellate cells (HSCs) is a promising therapeutic strategy against hepatitis B virus (HBV)-related hepatic fibrosis. The underlying mechanisms of apoptosis in HSCs, however, are unknown under consideration of HBV infection. In this study, the effects of HBV on apoptosis and endoplasmic reticulum (ER) stress signaling in HSCs were examined. Methods The effects of conditioned media (CM) from HepG2.2.15 on apoptosis induced by the proteasome inhibitor MG132 in LX-2 and HHSteC were studied in regard to c-Jun. In combination with c-Fos, c-Jun forms the AP-1 early response transcription factor, leading to AP-1 activation, signal transduction, endoplasmic reticulum (ER) stress and apoptosis. Results In LX-2 cells, MG132 treatment was associated with the phosphorylation of c-Jun, activation of AP-1 and apoptosis. However, in the presence of CM from HepG2.2.15, these phenomena were attenuated. In HHSteC cells, similar results were observed. HBV genomic DNA is not involved in the process of HSC apoptosis. It is possible that HBeAg has an inhibitory effect on MG132-induced apoptosis in LX-2. We also observed the upregulation of several ER stress-associated genes, such as cAMP responsive element binding protein 3-like 3, inhibin-beta A and solute carrier family 17-member 2, in the presence of CM from HepG2.2.15, or CM from PXB cells infected with HBV. Conclusions HBV inhibits the activation of c-Jun/AP-1 in HSCs, contributing to the attenuation of apoptosis and resulting in hepatic fibrosis. HBV also up-regulated several ER stress genes associated with cell growth and fibrosis. These mechanistic insights might shed new light on a treatment strategy for HBV-associated hepatic fibrosis. PMID:26731332

  17. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the {gamma}-glutamyl cycle

    SciTech Connect

    Stern, Stephan T.; Bruno, Mary K.; Horton, Robert A.; Hill, Dennis W.; Roberts, Jeanette C.; Cohen, Steven D. . E-mail: scohen@mcp.edu

    2005-01-15

    Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Our recent investigations have focused on the possible involvement of glutathione-derived APAP metabolites in APAP nephrotoxicity and have demonstrated that administration of acetaminophen-cysteine (APAP-CYS) potentiated APAP-induced renal injury with no effects on APAP-induced liver injury. Additionally, APAP-CYS treatment alone resulted in a dose-responsive renal GSH depletion. This APAP-CYS-induced renal GSH depletion could interfere with intrarenal detoxification of APAP or its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) and may be the mechanism responsible for the potentiation of APAP nephrotoxicity. Renal-specific GSH depletion has been demonstrated in mice and rats following administration of amino acid {gamma}-glutamyl acceptor substrates for {gamma}-glutamyl transpeptidase ({gamma}-GT). The present study sought to determine if APAP-CYS-induced renal glutathione depletion is the result of disruption of the {gamma}-glutamyl cycle through interaction with {gamma}-GT. The results confirmed that APAP-CYS-induced renal GSH depletion was antagonized by the {gamma}-glutamyl transpeptidase ({gamma}-GT) inhibitor acivicin. In vitro analysis demonstrated that APAP-CYS is a {gamma}-glutamyl acceptor for both murine and bovine renal {gamma}-GT. Analysis of urine from mice pretreated with acivicin and then treated with APAP, APAP-CYS, or acetaminophen-glutathione identified a {gamma}-glutamyl-cysteinyl-acetaminophen metabolite. These findings are consistent with the hypothesis that APAP-CYS contributes to APAP nephrotoxicity by depletion of renal GSH stores through interaction with the {gamma}-glutamyl cycle.

  18. Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling

    PubMed Central

    GUO, XUELING; SHANG, JIN; DENG, YAN; YUAN, XIAO; ZHU, DIE; LIU, HUIGUO

    2015-01-01

    Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6–8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH. PMID:25936416

  19. Antimanic-like activity of candesartan in mice: Possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms.

    PubMed

    de Souza Gomes, Júlia Ariana; de Souza, Greicy Coelho; Berk, Michael; Cavalcante, Lígia Menezes; de Sousa, Francisca Cléa F; Budni, Josiane; de Lucena, David Freitas; Quevedo, João; Carvalho, André F; Macêdo, Danielle

    2015-11-01

    Activation of the brain angiotensin II type 1 receptor (AT1R) triggers pro-oxidant and pro-inflammatory mechanisms which are involved in the neurobiology of bipolar disorder (BD). Candesartan (CDS) is an AT1 receptor antagonist with potential neuroprotective properties. Herein we investigated CDS effects against oxidative, neurotrophic inflammatory and cognitive effects of amphetamine (AMPH)-induced mania. In the reversal protocol adult mice were given AMPH 2 mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention treatment, mice were pretreated with CDS, Li or saline prior to AMPH. Locomotor activity and working memory performance were assessed. Glutathione (GSH), thiobarbituric acid-reactive substance (TBARS) and TNF-α levels were evaluated in the hippocampus (HC) and cerebellar vermis (CV). Brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK-3beta) levels were measured in the HC. CDS and Li prevented and reversed the AMPH-induced increases in locomotor activity. Only CDS prevented and reversed AMPH-induced working memory deficits. CDS prevented AMPH-induced alterations in GSH (HC and CV), TBARS (HC and CV), TNF-α (HC and CV) and BDNF (HC) levels. Li prevented alterations in BDNF and phospho-Ser9-GSK3beta. CDS reversed AMPH-induced alterations in GSH (HC and CV), TBARS (HC), TNF-α (CV) and BDNF levels. Li reversed AMPH-induced alterations in TNF-α (HC and CV) and BDNF (HC) levels. CDS is effective in reversing and preventing AMPH-induced behavioral and biochemical alterations, providing a rationale for the design of clinical trials investigating CDS׳s possible therapeutic effects. PMID:26321203

  20. Antiviral activity and possible mode of action of ellagic acid identified in Lagerstroemia speciosa leaves toward human rhinoviruses

    PubMed Central

    2014-01-01

    Background Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4. Methods The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin. Results As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 μg/mL), HRV-3 (31 μg/mL), and HRV-4 (29 μg/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 μg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 μg/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 μg/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules. Conclusions Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the

  1. Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel.

    PubMed

    Malysz, J; Richardson, D; Farraway, L; Christen, M O; Huizinga, J D

    1995-10-01

    Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18% and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel

  2. Forum: Knowledge, Action, Involvement

    ERIC Educational Resources Information Center

    Weinberger, JoAnn

    2015-01-01

    St. Clair (EJ1072357) provides a summary and lays out some of the important issues inherent in the broad strategies articulated in "Making Skills Everyone's Business: A Call to Transform Adult Learning in the United States" (MSEB) (United States Department of Education [USDoE], 2015) (see ED558793). In this commentary, JoAnn Weinberger…

  3. Nitric oxide-dependent NAD linkage to glyceraldehyde-3-phosphate dehydrogenase: possible involvement of a cysteine thiyl radical intermediate.

    PubMed Central

    Minetti, M; Pietraforte, D; Di Stasi, A M; Mallozzi, C

    1996-01-01

    Previous studies have demonstrated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) undergoes NAD(H) linkage to an active site thiol when it comes into contact with .NO-related oxidants. We found that a free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH), which does not release either .NO or .NO-related species, was indeed able to induce the NAD(H) linkage to GAPDH. We performed spin-trapping studies with purified apo-GAPDH to identify a putative thiol intermediate produced by AAPH as well as by .NO-related oxidants. As .NO sources we used .NO gas and two .NO-donors, S-nitroso-N-acetyl-D,L-penicillamine and 3-morpholinosydno-nimine hydrochloride (SIN-1). Because SIN-1 produces .NO and a superoxide radical simultaneously, we also tested the effects of peroxynitrite. All the .NO-related oxidants were able to induce the linkage of NAD(H) to GAPDH and the formation of a protein free-radical identified as a thiyl radical (inhibited by N-ethylmaleimide). .NO gas and the .NO-donors required molecular oxygen to induce the formation of the GAPDH thiyl radical, suggesting the possible involvement of higher nitrogen oxides. Thiyl radical formation was decreased by the reconstitution of GAPDH with NAD+. Apo-GAPDH was a strong scavenger of AAPH radicals, but its scavenging ability was decreased when its cysteine residues were alkylated or when it was reconstituted with NAD+. In addition, after treatment with AAPH, a thiyl radical of GAPDH was trapped at high enzyme concentrations. We suggest that the NAD(H) linkage to GAPDH is mediated by a thiyl radical intermediate not specific to .NO or .NO-related oxidants. The cysteine residue located at the active site of GAPDH (Cys-149) is oxidized by free radicals to a thiyl radical, which reacts with the neighbouring coenzyme to form Cys-NAD(H) linkages. Studies with the NAD+ molecule radio-labelled in the nicotinamide or adenine portion revealed that both portions of the NAD+ molecule are linked to GAPDH

  4. Effect on GLE Occurrence Distribution: Possible Action on Active Region by Earth and Jupiter Magnetospheres through Cosmic Ray Deflection

    NASA Astrophysics Data System (ADS)

    Del Pozo Garcia, Eduardo

    Eduardo del Pozo Garcia Geophysics and Astronomy Institute Havana, Cuba pozo@iga.cu Following Perez- Peraza and collaborators works on GLE prediction on basis to Cosmic Ray periodicities and cycles, in particular with 1,2 year cycle, effect prognosis of GLE occurrence was determine, I present here a possible interpretation of their results. Here I present the time distribution of the observed GLE in respect to each GLE nearly Sun-Earth-Jupiter alignment time. At the histogram the X axis cero is the alignment time. These alignments take place cyclically every 1,1 year. The histogram shows a modulation-like GLE distribution. The occurrence increments are near the alignment time and, about 125 days before and after the alignment time. Besides, a work hypothesis is proposed: “The Jupiter and Earth magnetospheres must deflect cosmic rays and, at some Jupiter and Earth positions according the current interplanetary magnetic field, may be favorable to increase the energetic particle flux over current Sun active regions, giving place to a modulation-like GLE distribution. Also, by the cosmic rays action some particle flux increase over active regions may come from radiation belts” This effect means that, during solar activity this is a factor that contributes to: - An accumulative activity increase of sunspot groups and their magnetic configuration complexity - Eventually, over complex active region some increase of high energy particle flux help to trigger GLE, or intensify solar proton events in progress, and become a GLE. This effect is taken into account for GLE prediction.

  5. Differential involvement of phosphoinositide 3-kinase in gonadotrophin-releasing hormone actions in gonadotrophs and somatotrophs of goldfish, Carassius auratus.

    PubMed

    Pemberton, Joshua G; Stafford, James L; Yu, Yi; Chang, John P

    2011-08-01

    In goldfish, two endogenous gonadotrophin-releasing hormones (GnRHs) [salmon (s)GnRH and chicken (c)GnRH-II] control maturational gonadotrophin-II [lutenising hormone (LH)] and growth hormone (GH) secretion via Ca(2+)-dependent intracellular signalling pathways. We investigated the involvement of phosphoinositide 3-kinase (PI3K) in GnRH-evoked LH and GH release and associated intracellular Ca(2+) increases ([Ca(2+)](i) ) in goldfish gonadotrophs and somatotrophs. Immunoreactive PI3K p85α, the predominant regulatory subunit for class IA PI3Ks, was detected in goldfish pituitary tissue extracts and both endogenous GnRH isoforms increased phosphorylation of PI3K p85α in excised pituitary fragments. sGnRH- and cGnRH-II-elicited LH release responses from primary cultures of pituitary cells and [Ca(2+)](i) increases in identified gonadotrophs were significantly reduced in the presence of PI3K inhibitors wortmannin (100 nm) and LY294002 (10 μm). Unexpectedly, wortmannin and LY294002 inhibited GnRH-evoked GH release but only attenuated the [Ca(2+)](i) response in identified somatotrophs to cGnRH-II, and not sGnRH. On the other hand, Ca(2+) ionophore-evoked LH and GH secretion remained unaltered in the presence of the PI3K inhibitors, suggesting that general decreases in the releasable hormone pool or sensitivity to [Ca(2+)](i) changes did not underlie the ability of wortmannin and LY294002 to reduce the actions of GnRH. These results provide the first evidence for the presence and involvement of PI3K in GnRH-induced LH and GH release in any primary pituitary cell system. In gonadotrophs, the inhibitory action of PI3K on both sGnRH and cGnRH-II involves the attenuation of their evoked [Ca(2+)](i); in contrast, GnRH isoform-specific effects occur in somatotrophs. PMID:21649760

  6. Involvement of L-arginine/NO/cGMP/K(ATP) channel pathway in the peripheral antinociceptive actions of ellagic acid in the rat formalin test.

    PubMed

    Ghorbanzadeh, Behnam; Mansouri, Mohammad Taghi; Hemmati, Ali Asghar; Naghizadeh, Bahareh; Mard, Seyyed Ali; Rezaie, Anahita

    2014-11-01

    The present study was conducted to evaluate the local antinociceptive actions of EA and the possible involvement of l-arginine/NO/cGMP/KATP channel pathway in this effect using formalin test in rats. To evaluate the involvement of l-arginine/NO/cGMP/KATP channel pathway in the antinociceptive action of EA, rats were pre-treated intraplantarlly with l-NAME (NOS inhibitor, 25-100μg/paw), methylene blue (guanylyl cyclase inhibitor, 100-400μg/paw), glibenclamide (ATP-sensitive K(+) channel blocker, 25-100μg/paw), l-arginine (a nitric oxide precursor, 25-100μg/paw) and sodium nitroprusside (125-500μg/paw). The local peripheral ipsilateral, but not contralateral, administration of EA into the right paw (30-300μg/paw) produced a dose-related antinociception during both early and late phases of formalin test which is comparable with morphine (25μg/paw). Moreover, local pre-treatment with l-NAME, methylene blue and glibenclamide dose-dependently prevented EA (100μg/paw)-induced antinociception in late phase. Additionally, administration of l-arginine and sodium nitroprusside significantly potentiated the antinociception induced by EA in the late phase. However, these treatments had no significant effect on antinociceptive response of EA in the early phase of the formalin test. The results of the present study showed that EA-induced local peripheral antinociception during the both phases of formalin test. Also, our data suggested the activation of the l-arginine/NO/cGMP/KATP channels pathway in EA-induced antinociception in late phase of formalin test. Topical application of EA by ointment or jelly might be a useful method to relieving the inflammatory pain states. PMID:25278343

  7. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action

    PubMed Central

    Fonseca-Silva, Fernanda; Inacio, Job D. F.; Canto-Cavalheiro, Marilene M.; Menna-Barreto, Rubem F. S.; Almeida-Amaral, Elmo E.

    2016-01-01

    Background The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. Methodology/Principal Finding Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health

  8. Mechanism of action of peptidoglycan O-acetyltransferase B involves a Ser-His-Asp catalytic triad.

    PubMed

    Moynihan, Patrick J; Clarke, Anthony J

    2014-10-01

    The O-acetylation of the essential cell wall polymer peptidoglycan is essential in many bacteria for their integrity and survival, and it is catalyzed by peptidoglycan O-acetlytransferase B (PatB). Using PatB from Neisseria gonorrhoeae as the model, we have shown previously that the enzyme has specificity for polymeric muropeptides that possess tri- and tetrapeptide stems and that rates of reaction increase with increasing degrees of polymerization. Here, we present the catalytic mechanism of action of PatB, the first to be described for an O-acetyltransferase of any bacterial exopolysaccharide. The influence of pH on PatB activity was investigated, and pKa values of 6.4-6.45 and 6.25-6.35 for the enzyme-substrate complex (kcat vs pH) and the free enzyme (kcat·KM(-1) vs pH), respectively, were determined for the respective cosubstrates. The enzyme is partially inactivated by sulfonyl fluorides but not by EDTA, suggesting the participation of a serine residue in its catalytic mechanism. Alignment of the known and hypothetical PatB amino acid sequences identified Ser133, Asp302, and His305 as three invariant amino acid residues that could potentially serve as a catalytic triad. Replacement of Asp302 with Ala resulted in an enzyme with less than 20% residual activity, whereas activity was barely detectable with (His305 → Ala)PatB and (Ser133 → Ala)PatB was totally inactive. The reaction intermediate of the transferase reaction involving acetyl- and propionyl-acyl donors was trapped on both the wild-type and (Asp302 → Ala) enzymes and LC-MS/MS analysis of tryptic peptides identified Ser133 as the catalytic nucleophile. A transacetylase mechanism is proposed based on the mechanism of action of serine esterases. PMID:25215566

  9. Schistosoma mansoni: possible involvement of protein kinase C in linoleic acid-induced proteolytic enzyme release from cercariae.

    PubMed

    Matsumura, K; Mitsui, Y; Sato, K; Sakamoto, M; Aoki, Y

    1991-04-01

    The possible involvement of protein kinase C and Ca2+ metabolism in the proteolytic enzyme release from schistosome cercariae was studied. Cercariae were placed in dechlorinated tap water containing 0.37 mM calcium in the small glass petri dish and exposed to the stimuli (linoleic acid, phorbol esters, and Ca2+ ionophore) with or without inhibitors of protein kinase C or Ca2+ metabolism. The proteolytic activity of incubation medium of cercariae thus treated was measured by the azocoll assay. The penetration response of cercariae induced by linoleic acid, a physiological stimulus, was mimicked by phorbol esters. When exposed to phorbol esters, 0.02 to 2 microM of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 0.2 to 2 microM of phorbol-12,13-dibutyrate (PDBu), cercariae ceased the swimming movement, began a rhythmic thrusting of the anterior tip of the parasite, and released the proteolytic enzyme, but they did not shed the tails. Lowering Ca2+ in water by addition of 5 mM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), phorbol ester-induced release of enzyme was completely inhibited. Phorbol ester-induced release of enzyme was partially inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C, at a concentration of 100 microM. H-7 alone, at a concentration of 100 microM, did not affect the swimming movement of cercariae. The cercariae were stimulated to release the enzyme by high concentrations (10 and 100 microM) of the Ca2+ ionophore, A23187, but enzyme was not released by low concentrations (0.5 and 1 microM) of this drug. Cercariae exposed to A23187 behaved differently from those exposed to phorbol esters. They ceased swimming, showed strong muscle contraction, and shed their tail. A23187 stimulated cercariae to release the enzyme in the water containing 5 mM EGTA. A23187-induced enzyme release was not inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin

  10. Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action

    PubMed Central

    2011-01-01

    Background Magnolol, a plant lignan isolated from the bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically-induced skin cancer development. The objectives of this investigation are to study the anticarcinogenic effects of magnolol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and determine the possible role of apoptosis and cell cycle arrest involved in the skin tumor development. Methods UVB-induced skin carcinogenesis model in SKH-1 mice was used for determining the preventive effects of magnolol on skin cancer development. Western blottings and flow cytometric analysis were used to study the effects of magnolol on apoptosis and cell cycle. Results Magnolol pretreated groups (30, 60 μ g) before UVB treatments (30 mJ/cm2, 5 days/week) resulted in 27-55% reduction in tumor multiplicity as compared to control group in SKH-1 mice. Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21, a cell cycle inhibitor, and decreased the expression of proteins involved in the G2/M phase of cell cycle in skin samples from SKH-1 mice. Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner. Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h with a decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2 and simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor. Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP. Phospho-signal transducers and activators of transcription 3 (Tyr705), B-Raf, p-MEK, and p-AKT were down-regulated, whereas phosphorylation of ERK was induced by magnolol in A431 cells. Conclusions Magnolol pretreatments prevent UVB-induced skin cancer development by enhancing apoptosis, causing cell cycle arrest at G2/M

  11. Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice.

    PubMed

    Kumar, Anil; Singh, Anant

    2009-08-01

    Sleep is an important physiological process responsible for the maintenance of physical, mental and emotional health of a living being. Sleep deprivation is considered risky for several pathological diseases such as anxiety and motor and cognitive dysfunctions. Sleep deprivation has recently been reported to cause oxidative damage. This study has been designed to explore the possible involvement of the GABAergic mechanism in protective effects of melatonin against 72-h sleep deprivation-induced behaviour modification and oxidative damage in mice. Mice were sleep-deprived for a period of 72 h using the grid over water suspended method. Animals were divided into groups of 6-8 animals each. Melatonin (5 and 10 mg/kg), flumazenil (0.5 mg/kg), picrotoxin (0.5 mg/kg) and muscimol (0.05 mg/kg) were administered for 5 days starting 2 days before 72-h sleep deprivation. Various behavioural tests (plus maze, zero maze, mirror chamber, actophotometer) and body weight assessment followed by oxidative stress parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were carried out. The 72-h sleep deprivation caused significant anxiety-like behaviour, weight loss, impaired locomotor activity and oxidative damage as compared with naïve (without sleep deprivation). Treatment with melatonin (5 mg/kg and 10 mg/kg, ip) significantly improved locomotor activity, weight loss and antianxiety effect as compared with control (sleep-deprived). Biochemically, melatonin treatment significantly restored reduced glutathione, catalase activity, attenuated lipid peroxidation and nitrite level as compared with control animals (72-h sleep-deprived). Flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) pretreatments with a lower dose of melatonin (5 mg/kg) significantly antagonized the protective effect of melatonin. However, muscimol (0.05 mg/kg) pretreatment with melatonin (5 mg/kg, ip) potentiated the protective effect of melatonin which was significant as compared with their

  12. Bacillus thuringiensis Cry1A toxins are versatile proteins with multiple modes of action: two distinct pre-pores are involved in toxicity

    PubMed Central

    Gómez, Isabel; Sánchez, Jorge; Muñoz-Garay, Carlos; Matus, Violeta; Gill, Sarjeet S.; Soberón, Mario; Bravo, Alejandra

    2014-01-01

    Cry proteins from Bacillus thuringiensis are insecticidal PFTs (pore-forming toxins). In the present study, we show that two distinct functional pre-pores of Cry1Ab are formed after binding of the protoxin or the protease-activated toxin to the cadherin receptor, but before membrane insertion. Both pre-pores actively induce pore formation, although with different characteristics, and contribute to the insecticidal activity. We also analysed the oligomerization of the mutant Cry1AbMod protein. This mutant kills different insect populations that are resistant to Cry toxins, but lost potency against susceptible insects. We found that the Cry1AbMod-protoxin efficiently induces oligomerization, but not the activated Cry1AbMod-toxin, explaining the loss of potency of Cry1AbMod against susceptible insects. These data are relevant for the future control of insects resistant to Cry proteins. Our data support the pore-formation model involving sequential interaction with different midgut proteins, leading to pore formation in the target membrane. We propose that not only different insect targets could have different receptors, but also different midgut proteases that would influence the rate of protoxin/toxin activation. It is possible that the two pre-pore structures could have been selected for in evolution, since they have differential roles in toxicity against selected targets, increasing their range of action. These data assign a functional role for the protoxin fragment of Cry PFTs that was not understood previously. Most PFTs produced by other bacteria are secreted as protoxins that require activation before oligomerization, to finally form a pore. Thus different pre-pores could be also part of the general mechanism of action of other PFTs. PMID:24456341

  13. Combining sound science, legal action and stakeholder involvement to protect a vulnerable coastal aquifer on the island of St. Kitts

    NASA Astrophysics Data System (ADS)

    Sahely, H.; Nettles, S.; Burrowes, R.; Haas, G.

    2011-12-01

    Water resources in small island developing states (SIDS), especially those in the Caribbean are among the most vulnerable systems to human activities and climate change. This vulnerability is exacerbated by a fragmented approach to water resources management. The unconfined coastal aquifer underlying the Basseterre Valley is a significant asset for the people of St. Kitts-Nevis. The potable water extracted from this aquifer represents over 40% of the total water supply for St. Kitts. The area is subject to urban encroachment, inappropriate land use and threats from pollution. A project was implemented using an integrated approach to help government and communities take practical actions to protect this vulnerable aquifer by demonstrating proper management on three fronts: mitigation of threats from contaminants, protection of the aquifer and improved water resources management. The project is funded by the Global Environment Facility (GEF) as part of the Integrating Watershed and Coastal Areas Management (IWCAM) project for Caribbean Small Island States. A comprehensive hydrogeologic evaluation of the aquifer was undertaken in order to aid in the development of a water resources management strategy for the Basseterre Valley Aquifer. Multi-electrode electrical resistivity (MER), a novel surface geophysical technique, was used to delineate the thickness and distribution of sediments throughout the aquifer, zones of increased porosity, zones of possible contamination and the fresh/salt water interface. Together with slowly declining static water levels and elevated dissolved solids levels, the early stages of salt water intrusion have been documented. Groundwater modelling suggests that adjusting the pumping regime, redeveloping some of the existing wells and relocating other wells is a viable option for increasing efficiency and preventing long term dewatering. Overall, the study has provided a wealth of new information about the aquifer for a reasonable cost. A

  14. Aldrin epoxidation in flathead mullet (Mugil cephalus): possible involvement of CYP1A and CYP3A.

    PubMed

    Bozcaarmutlu, Azra; Turna, Sema; Sapmaz, Canan; Arinc, Emel; Yenisoy-Karakaş, Serpil

    2014-06-01

    The primary objective of this study was to determine specific cytochrome P450 isozyme(s) involved in the metabolism of aldrin to its toxic metabolite dieldrin in flathead mullet (Mugil cephalus) liver microsomes. To identify the cytochrome P450 isozyme responsible for the aldrin metabolism in mullet liver, the effects of mammalian-specific cytochrome P450 inhibitors and substrates were determined in the epoxidation reaction of aldrin. CYP3A-related inhibitors, ketoconazole, SKF-525A, and cimetidine, inhibited the metabolism of aldrin. The contribution of CYP1A to the aldrin metabolism was shown by the inhibition of 7-ethoxyresorufin-O-deethylase activity in the presence of aldrin. The results indicate that CY1A and CYP3A are the cytochrome P450s involved in aldrin epoxidase activity in mullet. In addition, the suitability of aldrin epoxidase activity for monitoring of environmental pollution was also assessed in the fish samples caught from four different locations of the West Black Sea coast of Turkey. PMID:24756956

  15. Involvement of opioid receptors in the systemic and peripheral antinociceptive actions of montelukast in the animal models of pain.

    PubMed

    Ghorbanzadeh, Behnam; Mansouri, Mohammad Taghi; Sahraei, Hedayat; Alboghobeish, Soheila

    2016-05-15

    This study aimed to investigate the involvement of opioid receptors in the systemic and peripheral antinociceptive activities of montelukast in different animal models of pain. Rats and mice were injected with montelukast to produce analgesia. The formalin and acetic acid-induced writhing tests were used to assess the nociceptive activity. The results showed that i.p. administration of montelukast (0.3-10mg/kg) dose-dependently reduced flinching behavior in both the first and second phases of formalin test with mean ED50 of 0.55 and 5.31mg/kg, respectively. Also, intraplantar administration of montelukast (3-30μg/paw) produced antinociception against the two phases of formalin assay in a dose-dependent way with mean ED30 of 2.92 and 8.11μg/paw, respectively. Furthermore, pre-treatment with naloxone (a non-selective opioid receptor antagonist) significantly inhibited both the systemic and also peripheral antinociceptive actions of montelukast in formalin test. In writhing test, the results showed that intraperitoneal administration of montelukast (3-10mg/kg) significantly reduced the writhe number induced by acetic acid in mice. Moreover, co-administration of non-effective doses of montelukast (0.3 and 1mg/kg; i.p.) and morphine (0.25mg/kg; i.p.) significantly decreased the writhes number induced by acetic acid. Also, this effect was naloxone-reversible. These findings suggest that the systemic and peripheral antinociception produced by montelukast were mediated through the opioid receptors in central and peripheral nervous systems. Moreover, combination of montelukast and morphine could be noted as a new strategy for pain relief. PMID:26948314

  16. Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

    PubMed Central

    Madlala, Hlengiwe P.; Metzinger, Thomas; van Heerden, Fanie R.; Mubagwa, Kanigula; Dessy, Chantal

    2016-01-01

    Purpose Plant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C. Methods Cell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors. Results OA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-ω-Nitro-L-arginine. A combination of both ATP-dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation. Conclusion These data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart. PMID:26799746

  17. Polymorphisms in the interleukin-10 gene cluster are possibly involved in the increased risk for major depressive disorder

    PubMed Central

    Traks, Tanel; Koido, Kati; Eller, Triin; Maron, Eduard; Kingo, Külli; Vasar, Veiko; Vasar, Eero; Kõks, Sulev

    2008-01-01

    Background Innate immune inflammatory response is suggested to have a role in the pathogenesis of major depressive disorder (MDD). Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 are all implicated in the inflammatory processes and polymorphisms in respective genes have been associated with various immunopathological conditions. This study was carried out to investigate whether single-nucleotide polymorphisms (SNPs) in these genes are also associated with MDD. Methods Case-control association study was performed with seven SNPs from the IL10 gene cluster. 153 patients with MDD and 277 healthy control individuals were recruited. Results None of the selected SNPs were individually associated with MDD. The linkage disequilibrium (LD) analysis indicated the existence of two recombination sites in the IL10 gene cluster, thus confirming the formerly established LD pattern of this genomic region. This also created two haplotype blocks, both consisting of three SNPs. Additionally, the haplotype analysis detected a significantly higher frequency of block 2 (IL20 and IL24 genes) haplotype TGC in the patients group compared to healthy control individuals (P = 0.0097). Conclusion Our study established increased risk for MDD related to the IL20 and IL24 haplotype and suggests that cytokines may contribute to the pathogenesis of MDD. Since none of the block 2 SNPs were individually associated with MDD, it is possible that other polymorphisms linked to them contribute to the disease susceptibility. Future studies are needed to confirm the results and to find the possible functional explanation. PMID:19087313

  18. Cloning and Expression Analysis of Vvlcc3, a Novel and Functional Laccase Gene Possibly Involved in Stipe Elongation

    PubMed Central

    Lu, Yuanping; Wu, Guangmei; Lian, Lingdan; Guo, Lixian; Wang, Wei; Yang, Zhiyun; Miao, Juan; Chen, Bingzhi; Xie, Baogui

    2015-01-01

    Volvariella volvacea, usually harvested in its egg stage, is one of the most popular mushrooms in Asia. The rapid transition from the egg stage to elongation stage, during which the stipe stretches to almost full length leads to the opening of the cap and rupture of the universal veil, and is considered to be one of the main factors that negatively impacts the yield and value of V. volvacea. Stipe elongation is a common phenomenon in mushrooms; however, the mechanisms, genes and regulation involved in stipe elongation are still poorly understood. In order to study the genes related to the stipe elongation, we analyzed the transcription of laccase genes in stipe tissue of V. volvacea, as some laccases have been suggested to be involved in stipe elongation in Flammulina velutipes. Based on transcription patterns, the expression of Vvlcc3 was found to be the highest among the 11 laccase genes. Moreover, phylogenetic analysis showed that VvLCC3 has a high degree of identity with other basidiomycete laccases. Therefore, we selected and cloned a laccase gene, named Vvlcc3, a cDNA from V. volvacea, and expressed the cDNA in Pichia pastoris. The presence of the laccase signature L1-L4 on the deduced protein sequence indicates that the gene encodes a laccase. Phylogenetic analysis showed that VvLCC3 clusters with Coprinopsis cinerea laccases. The ability to catalyze ABTS (2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation proved that the product of the Vvlcc3 gene was a functional laccase. We also found that the expression of the Vvlcc3 gene in V. volvacea increased during button stage to the elongation stage; it reached its peak in the elongation stage, and then decreased in the maturation stage, which was similar to the trend in the expression of Fv-lac3 and Fv-lac5 in F. velutipes stipe tissue. The similar trend in expression level of these laccase genes of F. velutipes suggested that this gene could be involved in stipe elongation in V. volvacea. PMID

  19. Cloning and Expression Analysis of Vvlcc3, a Novel and Functional Laccase Gene Possibly Involved in Stipe Elongation.

    PubMed

    Lu, Yuanping; Wu, Guangmei; Lian, Lingdan; Guo, Lixian; Wang, Wei; Yang, Zhiyun; Miao, Juan; Chen, Bingzhi; Xie, Baogui

    2015-01-01

    Volvariella volvacea, usually harvested in its egg stage, is one of the most popular mushrooms in Asia. The rapid transition from the egg stage to elongation stage, during which the stipe stretches to almost full length leads to the opening of the cap and rupture of the universal veil, and is considered to be one of the main factors that negatively impacts the yield and value of V. volvacea. Stipe elongation is a common phenomenon in mushrooms; however, the mechanisms, genes and regulation involved in stipe elongation are still poorly understood. In order to study the genes related to the stipe elongation, we analyzed the transcription of laccase genes in stipe tissue of V. volvacea, as some laccases have been suggested to be involved in stipe elongation in Flammulina velutipes. Based on transcription patterns, the expression of Vvlcc3 was found to be the highest among the 11 laccase genes. Moreover, phylogenetic analysis showed that VvLCC3 has a high degree of identity with other basidiomycete laccases. Therefore, we selected and cloned a laccase gene, named Vvlcc3, a cDNA from V. volvacea, and expressed the cDNA in Pichia pastoris. The presence of the laccase signature L1-L4 on the deduced protein sequence indicates that the gene encodes a laccase. Phylogenetic analysis showed that VvLCC3 clusters with Coprinopsis cinerea laccases. The ability to catalyze ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation proved that the product of the Vvlcc3 gene was a functional laccase. We also found that the expression of the Vvlcc3 gene in V. volvacea increased during button stage to the elongation stage; it reached its peak in the elongation stage, and then decreased in the maturation stage, which was similar to the trend in the expression of Fv-lac3 and Fv-lac5 in F. velutipes stipe tissue. The similar trend in expression level of these laccase genes of F. velutipes suggested that this gene could be involved in stipe elongation in V. volvacea. PMID

  20. Inositolphosphoglycans are possible mediators of the glucagon-like peptide 1 (7-36)amide action in the liver.

    PubMed

    Trapote, M A; Clemente, F; Galera, C; Morales, M; Alcántara, A I; López-Delgado, M I; Villanueva-Peñacarrillo, M L; Valverde, I

    1996-02-01

    A potent glycogenic effect for GLP-1(7-36)amide has been found in rat hepatocytes and skeletal muscle, and the specific receptors detected for GLP-1(7-36)amide in these tissue membranes do not seem to be associated to adenylate cyclase. On the other hand, inositolphosphoglycan molecules (IPGs) have been implicated as second messengers in the action of insulin. In a human hepatoma cell line (HEP G-2), we have observed the presence of [125I]GLP-1(7-36)amide specific binding, and a stimulatory effect of the peptide upon glycogen synthesis, confirming the findings in isolated rat hepatocytes. Also, GLP-1(7-36)amide modulates the cell content of radiolabelled glycosylphosphatidylinositols (GPIs), in the same manner as insulin, indicating hydrolysis of GPIs and an immediate and short-lived generation of IPGs. Thus, IPGs could be mediators in the GLP-1(7-36)amide glycogenic action in the liver. PMID:8778163

  1. Serotonin effects in the crab Neohelice granulata: Possible involvement of two types of receptors in peripheral tissues.

    PubMed

    Inohara, Elen Thegla Sander; Pinto, Charles Budazewsky; Model, Jorge Felipe Argenta; Trapp, Márcia; Kucharski, Luiz Carlos; Da Silva, Roselis Silveira Martins; Vinagre, Anapaula Sommer

    2015-07-01

    In crustaceans, serotonin (5-HT) controls various physiological processes, such as hormonal secretion, color changes, reproduction, and metabolism. Since 5-HT injections cause hyperglycemia, this study was designed to further investigate this action of 5-HT in the crab Neohelice granulate, fed with a high-carbohydrate (HC) or a high-protein (HP) diet. The effects of pre-treatment with mammalian 5-HT receptor antagonists, cyproheptadine and methiothepin, were also investigated. A series of in vivo experiments with (3)H-5-HT was carried out in order to investigate the presence of putative receptors in peripheral tissues. Since gills were the tissue with the highest labeling in in vivo experiments, in vitro studies with isolated anterior and posterior gills were also conducted. Cyproheptadine blocked the hyperglycemic effect of 5-HT in HP-fed crabs. Methiothepin reduced glycogen levels in the anterior gills of HP crabs and partially blocked the 5-HT-like posture. The injection of (3)H-5-HT identified specific binding sites in all the tissues studied and revealed that the binding can be influenced by the type of diet administered to the crabs. Incubation of the anterior and posterior gills with (3)H-5-HT and 5-HT confirmed the specificity of the binding sites. Both antagonists inhibited (3)H-5-HT binding. In conclusion, this study highlights the importance of serotonin in the control of glucose homeostasis in crustaceans and provides evidences of at least two types of 5-HT binding sites in peripheral tissues. Further studies are necessary to identify the structure of these receptors and their signaling pathways. PMID:25810362

  2. Identification of Proteins Possibly Involved in Glucosinolate Metabolism in L. agilis R16 and E. coli VL8.

    PubMed

    Luang-In, Vijitra; Narbad, Arjan; Cebeci, Fatma; Bennett, Mark; Rossiter, John T

    2015-04-01

    This study was aimed to identify sinigrin-induced bacterial proteins potentially involved in the metabolism of glucosinolate in two glucosinolate-metabolising bacteria Lactobacillus agilis R16 and Escherichia coli VL8. Sinigrin (2 mM) was used to induce the proteins in both bacteria under anaerobic incubation for 8 h at 30 °C for L. agilis R16 and 37 °C for E. coli VL8 and the controls without sinigrin were performed. Allyl isothiocyanate and allyl nitrile as two degradation products of sinigrin were detected in sinigrin-induced cultures of L. agilis R16 (27% total products) and E. coli VL8 (38% total products) from a complete sinigrin degradation in 8 h for both bacteria. 2D gel electrophoresis was conducted to identify induced proteins with at least twofold increased abundance. Sinigrin-induced L. agilis R16 and the control produced 1561 and 1543 protein spots, respectively. For E. coli VL8, 1363 spots were detected in sinigrin-induced and 1354 spots in the control. A combination of distinct proteins and upregulated proteins of 32 and 35 spots in L. agilis R16 and E. coli VL8, respectively were detected upon sinigrin induction. Of these, 12 and 16 spots from each bacterium respectively were identified by LC-MS/MS. In both bacteria most of the identified proteins are involved in carbohydrate metabolism, oxidoreduction system and sugar transport while the minority belong to purine metabolism, hydrolysis, and proteolysis. This indicated that sinigrin induction led to the expressions of proteins with similar functions in both bacteria and these proteins may play a role in bacterial glucosinolate metabolism. PMID:25805049

  3. Mutations in RIT1 cause Noonan syndrome with possible juvenile myelomonocytic leukemia but are not involved in acute lymphoblastic leukemia.

    PubMed

    Cavé, Hélène; Caye, Aurélie; Ghedira, Nehla; Capri, Yline; Pouvreau, Nathalie; Fillot, Natacha; Trimouille, Aurélien; Vignal, Cédric; Fenneteau, Odile; Alembik, Yves; Alessandri, Jean-Luc; Blanchet, Patricia; Boute, Odile; Bouvagnet, Patrice; David, Albert; Dieux Coeslier, Anne; Doray, Bérénice; Dulac, Olivier; Drouin-Garraud, Valérie; Gérard, Marion; Héron, Delphine; Isidor, Bertrand; Lacombe, Didier; Lyonnet, Stanislas; Perrin, Laurence; Rio, Marlène; Roume, Joëlle; Sauvion, Sylvie; Toutain, Annick; Vincent-Delorme, Catherine; Willems, Marjorie; Baumann, Clarisse; Verloes, Alain

    2016-08-01

    Noonan syndrome is a heterogeneous autosomal dominant disorder caused by mutations in at least eight genes involved in the RAS/MAPK signaling pathway. Recently, RIT1 (Ras-like without CAAX 1) has been shown to be involved in the pathogenesis of some patients. We report a series of 44 patients from 30 pedigrees (including nine multiplex families) with mutations in RIT1. These patients display a typical Noonan gestalt and facial phenotype. Among the probands, 8.7% showed postnatal growth retardation, 90% had congenital heart defects, 36% had hypertrophic cardiomyopathy (a lower incidence compared with previous report), 50% displayed speech delay and 52% had learning difficulties, but only 22% required special education. None had major skin anomalies. One child died perinatally of juvenile myelomonocytic leukemia. Compared with the canonical Noonan phenotype linked to PTPN11 mutations, patients with RIT1 mutations appear to be less severely growth retarded and more frequently affected by cardiomyopathy. Based on our experience, we estimate that RIT1 could be the cause of 5% of Noonan syndrome patients. Because mutations found constitutionally in Noonan syndrome are also found in several tumors in adulthood, we evaluated the potential contribution of RIT1 to leukemogenesis in Noonan syndrome. We screened 192 pediatric cases of acute lymphoblastic leukemias (96 B-ALL and 96 T-ALL) and 110 cases of juvenile myelomonocytic leukemias (JMML), but detected no variation in these tumoral samples, suggesting that Noonan patients with germline RIT1 mutations are not at high risk to developing JMML or ALL, and that RIT1 has at most a marginal role in these sporadic malignancies. PMID:26757980

  4. Characterization of an exported monoglyceride lipase from Mycobacterium tuberculosis possibly involved in the metabolism of host cell membrane lipids

    PubMed Central

    Côtes, Karen; Dhouib, Rabeb; Douchet, Isabelle; Chahinian, Henri; deCaro, Alain; Carrière, Frédéric; Canaan, Stéphane

    2007-01-01

    The Rv0183 gene of the Mycobacterium tuberculosis H37Rv strain, which has been implicated as a lysophospholipase, was cloned and expressed in Escherichia coli. The purified Rv0183 protein did not show any activity when lysophospholipid substrates were used, but preferentially hydrolysed monoacylglycerol substrates with a specific activity of 290 units·mg−1 at 37 °C. Rv0183 hydrolyses both long chain di- and triacylglycerols, as determined using the monomolecular film technique, although the turnover was lower than with MAG (monoacyl-glycerol). The enzyme shows an optimum activity at pH values ranging from 7.5 to 9.0 using mono-olein as substrate and is inactivated by serine esterase inhibitors such as E600, PMSF and tetrahydrolipstatin. The catalytic triad is composed of Ser110, Asp226 and His256 residues, as confirmed by the results of site-directed mutagenesis. Rv0183 shows 35% sequence identity with the human and mouse monoglyceride lipases and well below 15% with the other bacterial lipases characterized so far. Homologues of Rv0183 can be identified in other mycobacterial genomes such as Mycobacterium bovis, Mycobacterium smegmatis, and even Mycobacterium leprae, which is known to contain a low number of genes involved in the replication process within the host cells. The results of immunolocalization studies performed with polyclonal antibodies raised against the purified recombinant Rv0183 suggested that the enzyme was present only in the cell wall and culture medium of M. tuberculosis. Our results identify Rv0183 as the first exported lipolytic enzyme to be characterized in M. tuberculosis and suggest that Rv0183 may be involved in the degradation of the host cell lipids. PMID:17784850

  5. Inhibition by dizocilpine (MK-801) of striatal dopamine release induced by MPTP and MPP+: possible action at the dopamine transporter.

    PubMed

    Clarke, P B; Reuben, M

    1995-01-01

    1. The NMDA-type glutamate receptor antagonist, dizocilpine (MK-801) can protect against neurotoxicity associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its principal metabolite, the 1-methyl-4-phenylpyridinium ion (MPP+). It has been suggested that these neurotoxic effects may be mediated by release of excitatory amino acids, but possible alternative mechanisms have been little investigated. 2. MPTP and MPP+ (0.1-1000 microM) were tested in superfused rat striatal synaptosomes preloaded with [3H]-dopamine. Both MPTP (10 microM and higher) and MPP+ (1 microM and higher) evoked an immediate and concentration-dependent release of [3H]-dopamine. The maximal effect exceeded that achievable with nicotine. For subsequent experiments, submaximal concentrations of MPTP (50 microM) and MPP+ (10 microM) were tested. 3. MK-801 (0.1-100 microM) inhibited responses to MPTP (50 microM) and MPP+ (10 microM) in a concentration-dependent manner. However, further tests of NMDA-type glutamate receptor involvement proved negative. Responses to MPTP or MPP+ were unaffected by the omission of Mg2+ or Ca2+ and were not reduced by the NMDA receptor antagonists, AP-7 (200 microM) and kynurenic acid (300 microM). In this assay, N-methyl-D-aspartate (even in the absence of Mg2+ and with added glycine and strychnine) did not evoked [3H]-dopamine release. 4. In crude membrane preparations of rat cerebral cortex, MPTP and MPP+ inhibited high-affinity [3H]-nicotine binding to nicotinic cholinoceptors (IC50 1.8 microM and 26 microM, respectively). 5. [3H]-dopamine release evoked by nicotine (1 microM) was blocked by the nicotinic antagonists,mecamylamine and chlorisondamine, and by MK-801 (all at 100 micro M); K+-evoked release was not affected. Release evoked by MPTP and MPP+ was significantly attenuated by MK-801 but not by mecamylamine or chlorisondamine.6. At a high concentration (1O I1M), the selective dopamine uptake inhibitor, nomifensine, completely blocked [3HJ

  6. Single Muscle Immobilization Decreases Single-Fibre Myosin Heavy Chain Polymorphism: Possible Involvement of p38 and JNK MAP Kinases

    PubMed Central

    Derbré, Frédéric; Droguet, Mickaël; Léon, Karelle; Troadec, Samuel; Pennec, Jean-Pierre; Giroux-Metges, Marie-Agnès; Rannou, Fabrice

    2016-01-01

    Purpose Muscle contractile phenotype is affected during immobilization. Myosin heavy chain (MHC) isoforms are the major determinant of the muscle contractile phenotype. We therefore sought to evaluate the effects of muscle immobilization on both the MHC composition at single-fibre level and the mitogen-activated protein kinases (MAPK), a family of intracellular signaling pathways involved in the stress-induced muscle plasticity. Methods The distal tendon of female Wistar rat Peroneus Longus (PL) was cut and fixed to the adjacent bone at neutral muscle length. Four weeks after the surgery, immobilized and contralateral PL were dissociated and the isolated fibres were sampled to determine MHC composition. Protein kinase 38 (p38), extracellular signal-regulated kinases (ERK1/2), and c-Jun- NH2-terminal kinase (JNK) phosphorylations were measured in 6- and 15-day immobilized and contralateral PL. Results MHC distribution in immobilized PL was as follows: I = 0%, IIa = 11.8 ± 2.8%, IIx = 53.0 ± 6.1%, IIb = 35.3 ± 7.3% and I = 6.1 ± 3.9%, IIa = 22.1 ± 3.4%, IIx = 46.6 ± 4.5%, IIb = 25.2 ± 6.6% in contralateral muscle. The MHC composition in immobilized muscle is consistent with a faster contractile phenotype according to the Hill’s model of the force-velocity relationship. Immobilized and contralateral muscles displayed a polymorphism index of 31.1% (95% CI 26.1–36.0) and 39.3% (95% CI 37.0–41.5), respectively. Significant increases in p38 and JNK phosphorylation were observed following 6 and 15 days of immobilization. Conclusions Single muscle immobilization at neutral length induces a shift of MHC composition toward a faster contractile phenotype and decreases the polymorphic profile of single fibres. Activation of p38 and JNK could be a potential mechanism involved in these contractile phenotype modifications during muscle immobilization. PMID:27383612

  7. Molecular cloning of a new laccase from the edible straw mushroom Volvariella volvacea: possible involvement in fruit body development.

    PubMed

    Chen, Shicheng; Ge, Wei; Buswell, John A

    2004-01-30

    Cloning of a laccase-encoding cDNA from the edible straw mushroom, Volvariella volvacea, was performed using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. The cDNA of the putative laccase gene (lac4) consisted of 1689 bp, including an open reading frame encoding a 23-amino acid signal peptide at the N-terminal end and a 540-amino acid mature protein with a predicted molecular mass of 58173 Da and a pI value of 6.1. The 10 histidine residues and one cysteine residue required to co-ordinate the four copper atoms at the active site of the protein were all conserved. The amino acid sequence of V. volvacea lac4 has a high degree of identity with other basidiomycete laccases. Transcription of the laccase gene was analysed by RT-PCR and, unlike many other laccase genes, shown to be regulated independently of either copper or aromatic compounds under the test conditions. However, the laccase gene is strongly expressed during that part of the mushroom developmental cycle involving fruit body morphogenesis. PMID:14757236

  8. Identification of G Protein-Coupled Receptors (GPCRs) in Primary Cilia and Their Possible Involvement in Body Weight Control.

    PubMed

    Omori, Yoshihiro; Chaya, Taro; Yoshida, Satoyo; Irie, Shoichi; Tsujii, Toshinori; Furukawa, Takahisa

    2015-01-01

    Primary cilia are sensory organelles that harbor various receptors such as G protein-coupled receptors (GPCRs). We analyzed subcellular localization of 138 non-odorant GPCRs. We transfected GPCR expression vectors into NIH3T3 cells, induced ciliogenesis by serum starvation, and observed subcellular localization of GPCRs by immunofluorescent staining. We found that several GPCRs whose ligands are involved in feeding behavior, including prolactin-releasing hormone receptor (PRLHR), neuropeptide FF receptor 1 (NPFFR1), and neuromedin U receptor 1 (NMUR1), localized to the primary cilia. In addition, we found that a short form of dopamine receptor D2 (DRD2S) is efficiently transported to the primary cilia, while a long form of dopamine receptor D2 (DRD2L) is rarely transported to the primary cilia. Using an anti-Prlhr antibody, we found that Prlhr localized to the cilia on the surface of the third ventricle in the vicinity of the hypothalamic periventricular nucleus. We generated the Npy2r-Cre transgenic mouse line in which Cre-recombinase is expressed under the control of the promoter of Npy2r encoding a ciliary GPCR. By mating Npy2r-Cre mice with Ift80 flox mice, we generated Ift80 conditional knockout (CKO) mice in which Npy2r-positive cilia were diminished in number. We found that Ift80 CKO mice exhibited a body weight increase. Our results suggest that Npy2r-positive cilia are important for body weight control. PMID:26053317

  9. Macrophages in Langerhans cell histiocytosis are differentiated toward M2 phenotype: their possible involvement in pathological processes.

    PubMed

    Ohnishi, Koji; Komohara, Yoshihiro; Sakashita, Naomi; Iyama, Ken-Ichi; Murayama, Toshihiko; Takeya, Motohiro

    2010-01-01

    Although numerous macrophages are found in the lesions of Langerhans cell histiocytosis (LCH), their activation phenotypes and their roles in the disease process have not been clarified. Paraffin-embedded LCH samples were examined on immunohistochemistry and it was found that CD163 can be used to distinguish infiltrated macrophages from neoplastic Langerhans cells (LC). The number of CD163-positve macrophages was positively correlated with the number of multinucleated giant cells (MGC), indicating that most MGC are derived from infiltrated macrophages. A significant number of CD163-positive macrophages were positive for interleukin (IL)-10 and phospho-signal transducer and activator of transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This indicates that these macrophages are polarized to anti-inflammatory macrophages of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was considered to responsible for inducing M2 differentiation of infiltrated macrophages. The number of CD163-positive macrophages in different cases of LCH varied, and interestingly the density of CD163-positive macrophages was inversely correlated with the Ki-67-positivity of LC. Although the underlying mechanism is not fully elucidated, macrophage-derived IL-10 was considered to be involved in the suppression of tumor cell proliferation via activation of STAT3. PMID:20055949

  10. Trypsinlike enzymes from dormant and germinated spores of Bacillus cereus T and their possible involvement in germination.

    PubMed Central

    Boschwitz, H; Halvorson, H O; Keynan, A; Milner, Y

    1985-01-01

    Trypsin-like enzymes were studied in dormant, activated, and germinated spores of Bacillus cereus T. Dormant spores contained two heat-labile enzyme activities. One was extractable with 2 M KCl and hydrolyzed azo-albumin. The second, a trypsinlike activity, was not extractable with 2 M KCl and hydrolyzed benzoyl-L-arginine-p-nitroanilide. Because of their heat instability, these two enzyme activities are probably not involved in the germination of heat-activated spores. Upon germination of heat-treated spores, a trypsinlike protease which was not detected in intact dormant spores was activated or exposed. This enzyme, when measured in intact germinated spores, hydrolyzed benzoyl-DL-arginine-p-nitroanilide but not azo-albumin and was inhibited in situ by sulfhydryl-blocking reagents such as p-chloromercuribenzoic acid and Hg2+. There was a correlation between the inhibition of germination and enzymatic activity by sulfhydryl-blocking reagents. The enzyme was also inhibited by leupeptin, tosyl-L-lysine chromoethyl ketone, and tosyl-L-arginine methyl ester. Good correlation existed between the inhibition of germination and enzymatic activity by these agents. Electron micrographs showed that in the presence of trypsin inhibitors, the spores did not lose their cortex. The protein extracts of the inhibited spores formed a somewhat different electrophoretic pattern in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the protein extracts of dormant or germinated spores. Images PMID:3930468

  11. The antidepressant-like effect of bacopaside I: possible involvement of the oxidative stress system and the noradrenergic system.

    PubMed

    Liu, Xiaojun; Liu, Fang; Yue, Rongcai; Li, Yuanyuan; Zhang, Jigang; Wang, Shuping; Zhang, Shoude; Wang, Rui; Shan, Lei; Zhang, Weidong

    2013-09-01

    In the present study, the antidepressant-like effect of bacopaside I, a saponin compound present in the Bacopa monniera plant, was evaluated by behavioral and neurochemical methods. Bacopaside I (50, 15 and 5 mg/kg) was given to mice via oral gavage for 7 successive days. The treatment significantly decreased the immobility time in mouse models of despair tests, but it did not influence locomotor activity. Neurochemical assays suggested that treatment by bacopaside I (50, 15 and 5 mg/kg) improved brain antioxidant activity to varying degrees after the behavioral despair test. Bacopaside I (15 and 5 mg/kg) significantly reversed reserpine-induced depressive-like behaviors, including low temperature and ptosis. Conversely, bacopaside I did not affect either brain MAO-A or MAO-B activity after the behavioral despair test in mice. Additionally, 5-hydroxytryptophan (a precursor of 5-serotonin) was not involved in the antidepressant-like effect of bacopaside I. These findings indicated that the antidepressant-like effect of bacopaside I might be related to both antioxidant activation and noradrenergic activation, although the exact mechanism remains to be further elucidated. PMID:23872136

  12. Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance

    PubMed Central

    Dahan, P; Martinez Gala, J; Delmas, C; Monferran, S; Malric, L; Zentkowski, D; Lubrano, V; Toulas, C; Cohen-Jonathan Moyal, E; Lemarie, A

    2014-01-01

    Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover, recent studies showed that differentiated tumor cells may have the ability to dedifferentiate and acquire a stem-like phenotype, a phenomenon also called plasticity, in response to microenvironment stresses such as hypoxia. We hypothesized that GBM cells could be subjected to a similar dedifferentiation process after ionizing radiations (IRs), then supporting the GBM rapid recurrence after radiotherapy. In the present study we demonstrated that subtoxic IR exposure of differentiated GBM cells isolated from patient resections potentiated the long-term reacquisition of stem-associated properties such as the ability to generate primary and secondary neurospheres, the expression of stemness markers and an increased tumorigenicity. We also identified during this process an upregulation of the anti-apoptotic protein survivin and we showed that its specific downregulation led to the blockade of the IR-induced plasticity. Altogether, these results demonstrated that irradiation could regulate GBM cell dedifferentiation via a survivin-dependent pathway. Targeting the mechanisms associated with IR-induced plasticity will likely contribute to the development of some innovating pharmacological strategies for an improved radiosensitization of these aggressive brain cancers. PMID:25429620

  13. Genetic Evidence for Possible Involvement of the Calcium Channel Gene CACNA1A in Autism Pathogenesis in Chinese Han Population

    PubMed Central

    Yue, Weihua; Jia, Meixiang; Yu, Hao; Lu, Tianlan; Wu, Zhiliu; Ruan, Yanyan; Wang, Lifang; Zhang, Dai

    2015-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders. Recent studies suggested that calcium channel genes might be involved in the genetic etiology of ASD. CACNA1A, encoding an alpha-1 subunit of voltage-gated calcium channel, has been reported to play an important role in neural development. Previous study detected that a single nucleotide polymorphism (SNP) in CACNA1A confers risk to ASD in Central European population. However, the genetic relationship between autism and CACNA1A in Chinese Han population remains unclear. To explore the association of CACNA1A with autism, we performed a family-based association study. First, we carried out a family-based association test between twelve tagged SNPs and autism in 239 trios. To further confirm the association, the sample size was expanded to 553 trios by recruiting 314 additional trios. In a total of 553 trios, we identified association of rs7249246 and rs12609735 with autism though this would not survive after Bonferroni correction. Our findings suggest that CACNA1A might play a role in the etiology of autism. PMID:26566276

  14. Genetic Evidence for Possible Involvement of the Calcium Channel Gene CACNA1A in Autism Pathogenesis in Chinese Han Population.

    PubMed

    Li, Jun; You, Yang; Yue, Weihua; Jia, Meixiang; Yu, Hao; Lu, Tianlan; Wu, Zhiliu; Ruan, Yanyan; Wang, Lifang; Zhang, Dai

    2015-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders. Recent studies suggested that calcium channel genes might be involved in the genetic etiology of ASD. CACNA1A, encoding an alpha-1 subunit of voltage-gated calcium channel, has been reported to play an important role in neural development. Previous study detected that a single nucleotide polymorphism (SNP) in CACNA1A confers risk to ASD in Central European population. However, the genetic relationship between autism and CACNA1A in Chinese Han population remains unclear. To explore the association of CACNA1A with autism, we performed a family-based association study. First, we carried out a family-based association test between twelve tagged SNPs and autism in 239 trios. To further confirm the association, the sample size was expanded to 553 trios by recruiting 314 additional trios. In a total of 553 trios, we identified association of rs7249246 and rs12609735 with autism though this would not survive after Bonferroni correction. Our findings suggest that CACNA1A might play a role in the etiology of autism. PMID:26566276

  15. Antinociceptive effects of maprotiline in a rat model of peripheral neuropathic pain: possible involvement of opioid system

    PubMed Central

    Banafshe, Hamid Reza; Hajhashemi, Valiollah; Minaiyan, Mohsen; Mesdaghinia, Azam; Abed, Alireza

    2015-01-01

    Objective(s): Neuropathic pain remains a clinical problem and is poorly relieved by conventional analgesics. This study was designed to determine whether maprotiline administration was effective in alleviating symptoms of neuropathic pain and whether the antinociceptive effect of maprotiline mediated through the opioid system. Materials and Methods: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats, which resulted in thermal hyperalgesia, and mechanical and cold allodynia. Maprotiline (10, 20 and 40 mg/kg, IP) was administered on the 7th and 14th days after surgery. To study the role of the opioid system in the antinociceptive effects of maprotiline, maprotiline (20 mg/kg, IP) was administered in combination with naloxone (1 mg/kg, SC) on the 7th post-surgery day. Behavioral tests were done at 45 min after drug injections on the 7th and 14th days after surgery. Results: Systemic administration of maprotiline blocked heat hyperalgesia, cold allodynia and reduced mechanical allodynia. Also antihyperalgesic effect of maprotiline was reversed by pretreatment with naloxone. Conclusion: Our results suggest that maprotiline can be considered a potential therapeutic for the treatment of neuropathic pain, and the opioid system may be involved in the antihyperalgesic effects of maprotiline. PMID:26557963

  16. Isolation of putative glycoprotein gene from early somatic embryo of carrot and its possible involvement in somatic embryo development.

    PubMed

    Takahata, Kiminori; Takeuchi, Miyuki; Fujita, Minoru; Azuma, Junichi; Kamada, Hiroshi; Sato, Fumihiko

    2004-11-01

    Somatic embryogenesis is a unique process in plant cells. For example, embryogenic cells (EC) of carrot (Daucus carota) maintained in a medium containing 2,4-dichlorophenoxyacetic acid (2,4-D) regenerate whole plants via somatic embryogenesis after the depletion of 2,4-D. Although some genes such as C-ABI3 and C-LEC1 have been found to be involved in somatic embryogenesis, the critical molecular and cellular mechanisms for somatic embryogenesis are unknown. To characterize the early mechanism in the induction of somatic embryogenesis, we isolated genes expressed during the early stage of somatic embryogenesis after 2,4-D depletion. Subtractive hybridization screening and subsequent RNA gel blot analysis suggested a candidate gene, Carrot Early Somatic Embryogenesis 1 (C-ESE1). C-ESE1 encodes a protein that has agglutinin and S-locus-glycoprotein domains and its expression is highly specific to primordial cells of somatic embryo. Transgenic carrot cells with reduced expression of C-ESE1 had wide intercellular space and decreased polysaccharides on the cell surface and showed delayed development in somatic embryogenesis. The importance of cell-to-cell attachment in somatic embryogenesis is discussed. PMID:15574842

  17. Hydroxytyrosol inhibits phosphatidylserine exposure and suicidal death induced by mercury in human erythrocytes: Possible involvement of the glutathione pathway.

    PubMed

    Officioso, Arbace; Alzoubi, Kousi; Lang, Florian; Manna, Caterina

    2016-03-01

    Hydroxytyrosol (HT) is a phenolic antioxidant naturally occurring in virgin olive oil. In this study, we investigated the possible protective effects of HT on programmed suicidal death (eryptosis) induced by mercury (Hg) treatment in intact human erythrocytes (RBC). Our study confirms that the Hg-eryptosis is characterized by phosphatidylserine (PS) exposure at the cell surface, with cell shrinkage and ATP and glutathione depletion; calcium influx is also a key event that triggers eryptosis. Here we report that cell preconditioning with an optimal dose (1-5 μM) of HT prior to exposure to 2.5 μM HgCl2 causes a noteworthy decrease in PS-exposing RBC, almost restoring ATP and GSH content. Conversely, HT shows no effect against decrease in cell volume nor against influx of extracellular calcium. Taken together our data provide the first experimental evidence of the efficacy of HT in modulating the programmed suicidal death in non nucleated cells; the reported findings also confirm that the prevention of Hg toxicity should be regarded as an additional mechanism responsible for the health-promoting potential of this dietary phenol. Finally, virgin olive oil would appear to be a promising healthy food to reduce the adverse effects of chronic mercury exposure in humans. PMID:26774912

  18. Possible involvement of convergent nociceptive input to medullary dorsal horn neurons in intraoral hyperalgesia following peripheral nerve injury.

    PubMed

    Terayama, Ryuji; Tsuchiya, Hiroki; Omura, Shinji; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that the number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the medullary dorsal horn (MDH) evoked by noxious stimulation was increased after peripheral nerve injury, and such increase has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the MDH for convergent collateral primary afferent input to second order neurons deafferented by peripheral nerve injury, and to explore a possibility of its contribution to the c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input. c-Fos expression and the phosphorylation of ERK were induced by the intraoral application of capsaicin and by electrical stimulation of the inferior alveolar nerve (IAN), respectively. The number of c-Fos-IR neurons in the MDH induced by the intraoral application of capsaicin was increased after IAN injury, whereas the number of p-ERK immunoreactive neurons remained unchanged. The number of double-labeled neurons, that presumably received convergent primary afferent input from the lingual nerve and the IAN, was significantly increased after IAN injury. These results indicated that convergent primary nociceptive input through neighboring intact nerves may contribute to the c-Fos hyperinducibility in the MDH and the pathogenesis of neuropathic pain following trigeminal nerve injury. PMID:25407627

  19. Site-specific deletion in cauliflower mosaic virus DNA: possible involvement of RNA splicing and reverse transcription

    PubMed Central

    Hirochika, Hirohiko; Takatsuji, Hiroshi; Ubasawa, Aiko; Ikeda, Joh-E

    1985-01-01

    A frequent site-specific deletion was observed in the life cycle of cauliflower mosaic virus (S strain). Analysis of the sequence around the deletion site and the parental sequence implied that the deletion was promoted at sequences similar to the donor and acceptor consensus sequences of RNA splicing, designated as the deletion donor and acceptor sequences, respectively. To elucidate the mechanism of this site-specific deletion, point mutations were introduced into the deletion donor sequence (GT to GG or GA transversion). Deletion at the original deletion donor site did not occur in these mutants, instead, new (cryptic) donor sites were activated. All of these activated cryptic sites had sequences similar to the splicing consensus sequence. In all cases except one, the original deletion acceptor site was used. These results can be most readily explained by postulating that the site-specific deletion occurs by reverse transcription of spliced viral RNA. This frequent site-specific deletion was not observed in other strains. For a virus which replicates by reverse transcription, a mechanism to regulate the rate of splicing is required to ensure the intactness of the viral genome. We discuss the possibility that the S strain has a mutation in this regulatory mechanism. ImagesFig. 1.Fig. 3.Fig. 5.Fig. 7. PMID:16453624

  20. Hydroalcoholic extract of needles of Pinus eldarica enhances pentobarbital-induced sleep: possible involvement of GABAergic system

    PubMed Central

    Forouzanfar, Fatemeh; Ghorbani, Ahmad; Hosseini, Mahmoud; Rakhshandeh, Hassan

    2016-01-01

    Objective: Insomnia is accompanied by several health complications and the currently used soporific drugs can induce several side effects such as psychomotor impairment, amnesia, and tolerance. The present study was planned to investigate the sleep prolonging effect of Pinus eldarica. Materials and Methods: Hydroalcoholic extract (HAE) of P. eldarica, its water fraction (WF), ethyl acetate fraction (EAF) and n-butanol fraction (NBF) were injected (intraperitoneally) to mice 30 min before administration of pentobarbital. Then, the latent period and continuous sleeping time were recorded. Also, LD50 of P. eldarica extract was determined and the possible neurotoxicity of the extract was tested on neural PC12 cells. Results: The HAE and NBF decreased the latency of sleep (p<0.05) and significantly increased duration of sleep (p<0.05) induced by pentobarbital. These effects of P. eldarica were reversed by flumazenil. The LD50 value for HAE was found to be 4.8 g/Kg. HAE and its fractions did not show neurotoxic effects in cultured PC12-cell line. Conclusion: The present data indicate that P. eldarica potentiated pentobarbital hypnosis without major toxic effect. Most probably, the main components responsible for this effect are non-polar agents which are found in NBF of this plant. PMID:27516986

  1. Inhibition of Melanogenesis by the Pyridinyl Imidazole Class of Compounds: Possible Involvement of the Wnt/β-Catenin Signaling Pathway

    PubMed Central

    Bellei, Barbara; Pitisci, Angela; Izzo, Enzo; Picardo, Mauro

    2012-01-01

    While investigating the role of p38 MAPK in regulating melanogenesis, we found that pyridinyl imidazole inhibitors class compounds as well as the analog compound SB202474, which does not inhibit p38 MAPK, suppressed both α-MSH-induced melanogenesis and spontaneous melanin synthesis. In this study, we demonstrated that the inhibitory activity of the pyridinyl imidazoles correlates with inhibition of the canonical Wnt/β-catenin pathway activity. Imidazole-treated cells showed a reduction in the level of Tcf/Lef target genes involved in the β-catenin signaling network, including ubiquitous genes such as Axin2, Lef1, and Wisp1 as well as cell lineage-restricted genes such as microphthalmia-associated transcription factor and dopachrome tautomerase. Although over-expression of the Wnt signaling pathway effector β-catenin slightly restored the melanogenic program, the lack of complete reversion suggested that the imidazoles interfered with β-catenin-dependent transcriptional activity rather than with β-catenin expression. Accordingly, we did not observe any significant change in β-catenin protein expression. The independence of p38 MAPK activity from the repression of Wnt/β-catenin signaling pathway was confirmed by small interfering RNA knockdown of p38 MAPK expression, which by contrast, stimulated β-catenin-driven gene expression. Our data demonstrate that the small molecule pyridinyl imidazoles possess two distinct and opposite mechanisms that modulate β-catenin dependent transcription: a p38 inhibition-dependent effect that stimulates the Wnt pathway by increasing β-catenin protein expression and an off-target mechanism that inhibits the pathway by repressing β-catenin protein functionality. The p38-independent effect seems to be dominant and, at least in B16-F0 cells, results in a strong block of the Wnt/β-catenin signaling pathway. PMID:22427932

  2. Possible involvement of AMP-activated protein kinase in PGE1-induced synthesis of osteoprotegerin in osteoblasts

    PubMed Central

    KAINUMA, SHINGO; OTSUKA, TAKANOBU; KUROYANAGI, GEN; YAMAMOTO, NAOHIRO; MATSUSHIMA-NISHIWAKI, RIE; KOZAWA, OSAMU; TOKUDA, HARUHIKO

    2016-01-01

    AMP-activated protein kinase (AMPK) is firmly established as a central regulator of cellular energy homeostasis. We have previously reported that prostaglandin E1 (PGE1) stimulates the synthesis of osteoprotegerin through p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. The present study investigated the involvement of AMPK in PGE1-induced osteoprotegerin synthesis in MC3T3-E1 cells. The levels of osteoprotegerin were measured using an enzyme-linked immunosorbent assay, while the phosphorylation of AMPK, acetyl-CoA carboxylase, p38 MAP kinase and SAPK/JNK were analyzed by western blotting. In addition, the mRNA expression levels of osteoprotegerin were determined by a reverse transcription-quantitative polymerase chain reaction. It was revealed that PGE1 significantly induced the phosphorylation of the α and β subunits of AMPK in a time-dependent manner (P<0.05). In addition, acetyl-CoA carboxylase, a direct substrate of AMPK, was significantly phosphorylated by PGE1 (P<0.05). Compound C, an AMPK inhibitor, was revealed to suppress the phosphorylation of acetyl-CoA carboxylase, which significantly reduced the release and mRNA expression levels of PGE1-stimulated osteoprotegerin (P<0.05). However, the PGE1-induced phosphorylation of p38 MAP kinase and SAPK/JNK were not affected by compound C. The results of the present study indicated that AMPK may positively regulate PGE1-stimulated osteoprotegerin synthesis in osteoblasts; thus providing novel insight into the regulatory mechanisms underlying bone metabolism. PMID:27168848

  3. The Apparent Involvement of ANMEs in Mineral Dependent Methane Oxidation, as an Analog for Possible Martian Methanotrophy.

    PubMed

    House, Christopher H; Beal, Emily J; Orphan, Victoria J

    2011-01-01

    On Earth, marine anaerobic methane oxidation (AOM) can be driven by the microbial reduction of sulfate, iron, and manganese. Here, we have further characterized marine sediment incubations to determine if the mineral dependent methane oxidation involves similar microorganisms to those found for sulfate-dependent methane oxidation. Through FISH and FISH-SIMS analyses using 13C and 15N labeled substrates, we find that the most active cells during manganese dependent AOM are primarily mixed and mixed-cluster aggregates of archaea and bacteria. Overall, our control experiment using sulfate showed two active bacterial clusters, two active shell aggregates, one active mixed aggregate, and an active archaeal sarcina, the last of which appeared to take up methane in the absence of a closely-associated bacterial partner. A single example of a shell aggregate appeared to be active in the manganese incubation, along with three mixed aggregates and an archaeal sarcina. These results suggest that the microorganisms (e.g., ANME-2) found active in the manganese-dependent incubations are likely capable of sulfate-dependent AOM. Similar metabolic flexibility for Martian methanotrophs would mean that the same microbial groups could inhabit a diverse set of Martian mineralogical crustal environments. The recently discovered seasonal Martian plumes of methane outgassing could be coupled to the reduction of abundant surface sulfates and extensive metal oxides, providing a feasible metabolism for present and past Mars. In an optimistic scenario Martian methanotrophy consumes much of the periodic methane released supporting on the order of 10,000 microbial cells per cm2 of Martian surface. Alternatively, most of the methane released each year could be oxidized through an abiotic process requiring biological methane oxidation to be more limited. If under this scenario, 1% of this methane flux were oxidized by biology in surface soils or in subsurface aquifers (prior to release), a total

  4. Glycerophosphodiesterase GDE4 as a novel lysophospholipase D: a possible involvement in bioactive N-acylethanolamine biosynthesis.

    PubMed

    Tsuboi, Kazuhito; Okamoto, Yoko; Rahman, Iffat Ara Sonia; Uyama, Toru; Inoue, Tomohito; Tokumura, Akira; Ueda, Natsuo

    2015-05-01

    Bioactive N-acylethanolamines include anti-inflammatory palmitoylethanolamide, anorexic oleoylethanolamide, and an endocannabinoid arachidonoylethanolamide (anandamide). In animal tissues, these molecules are biosynthesized from N-acylethanolamine phospholipids directly by phospholipase D-type enzyme or through multi-step routes via N-acylethanolamine lysophospholipids. We previously found that mouse brain has a lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines and that this activity could be partially attributed to glycerophosphodiesterase (GDE) 1. In the present study, we examined catalytic properties of GDE4, another member of the GDE family. When overexpressed in HEK293 cells, murine GDE4 mostly resided in the membrane fraction. Purified GDE4 showed lysoPLD activity toward various lysophospholipids, including N-acylethanolamine lysophospholipids as well as lysophosphatidylethanolamine and lysophosphatidylcholine. When HEK293 cells were metabolically labeled with N-[(14)C]palmitoylethanolamine lysophospholipid, the transient expression of GDE4 increased the [(14)C]palmitoylethanolamide level, while the knockdown of endogenous GDE4 decreased this level. These results suggested that GDE4 functions as an N-acylethanolamine-generating lysoPLD in living cells. Moreover, the expression of GDE4 increased most species of lysophosphatidic acid (LPA), which can be produced from various lysophospholipids by the lysoPLD activity of GDE4. GDE4 mRNA was widely distributed among mouse tissues including brain, stomach, ileum, colon, and testis. In conclusion, GDE4 may act as a lysoPLD, which is involved in the generation of N-acylethanolamines and LPA. PMID:25596343

  5. DNase I and II present in avian oocytes: a possible involvement in sperm degradation at polyspermic fertilisation.

    PubMed

    Stepińska, Urszula; Olszańska, Bozenna

    2003-02-01

    During polyspermic fertilisation in birds numerous spermatozoa enter the eggs, in contrast to the situation in mammals where fertilisation is monospermic. However, in birds only one of the spermatozoa which have entered an egg participates in zygote nucleus formation, while the supernumerary spermatozoa degenerate at early embryogenesis. Our previous work has demonstrated the presence in preovulatory quail oocytes of DNase I and II activities able to digest naked lambdaDNA/HindIII substrate in vitro. In the present studies, the activities of both DNases in quail oocytes at different stages of oogenesis and in ovulated mouse oocytes were assayed in vitro using the same substrate. Degradation of quail spermatozoa by quail oocyte extracts was also checked. Digestion of the DNA substrate was evaluated by electrophoresis on agarose gels. The activities of DNase I and II in quail oocytes increased during oogenesis and were the highest in mature oocytes. The activities were present not only in germinal discs but also in a thin layer of cytoplasm adhering to the perivitelline layer surrounding the yolk. At all stages of oogenesis the activity of DNase II was much higher than that of DNase I. DNA contained in spermatozoa was also degraded by the quail oocyte extracts under conditions optimal for both DNases. In contrast to what is observed in quail oocytes, no DNase activities were detected in ovulated mouse eggs; this is logical as they would be useless or even harmful in monospermic fertilisation. The possible role of DNase activities in avian oocytes, in degradation of accessory spermatozoa during polyspermic fertilisation, is discussed. PMID:12625527

  6. Hydroxy-α sanshool induces colonic motor activity in rat proximal colon: a possible involvement of KCNK9.

    PubMed

    Kubota, Kunitsugu; Ohtake, Nobuhiro; Ohbuchi, Katsuya; Mase, Akihito; Imamura, Sachiko; Sudo, Yuka; Miyano, Kanako; Yamamoto, Masahiro; Kono, Toru; Uezono, Yasuhito

    2015-04-01

    Various colonic motor activities are thought to mediate propulsion and mixing/absorption of colonic content. The Japanese traditional medicine daikenchuto (TU-100), which is widely used for postoperative ileus in Japan, accelerates colonic emptying in healthy humans. Hydroxy-α sanshool (HAS), a readily absorbable active ingredient of TU-100 and a KCNK3/KCNK9/KCNK18 blocker as well as TRPV1/TRPA1 agonist, has been investigated for its effects on colonic motility. Motility was evaluated by intraluminal pressure and video imaging of rat proximal colons in an organ bath. Distribution of KCNKs was investigated by RT-PCR, in situ hybridization, and immunohistochemistry. Current and membrane potential were evaluated with use of recombinant KCNK3- or KCNK9-expressing Xenopus oocytes and Chinese hamster ovary cells. Defecation frequency in rats was measured. HAS dose dependently induced strong propulsive "squeezing" motility, presumably as long-distance contraction (LDC). TRPV1/TRPA1 agonists induced different motility patterns. The effect of HAS was unaltered by TRPV1/TRPA1 antagonists and desensitization. Lidocaine (a nonselective KCNK blocker) and hydroxy-β sanshool (a geometrical isomer of HAS and KCNK3 blocker) also induced colonic motility as a rhythmic propagating ripple (RPR) and a LDC-like motion, respectively. HAS-induced "LDC," but not lidocaine-induced "RPR," was abrogated by a neuroleptic agent tetrodotoxin. KCNK3 and KCNK9 were located mainly in longitudinal smooth muscle cells and in neural cells in the myenteric plexus, respectively. Administration of HAS or TU-100 increased defecation frequency in normal and laparotomy rats. HAS may evoke strong LDC possibly via blockage of the neural KCNK9 channel in the colonic myenteric plexus. PMID:25634809

  7. Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system.

    PubMed

    Seillier, Alexandre; Giuffrida, Andrea

    2016-02-01

    Previous studies have shown that social withdrawal in the phencyclidine (PCP) rat model of schizophrenia results from deficient endocannabinoid-induced activation of CB1 receptors. To understand the underlying cognitive mechanisms of the social deficit in PCP-treated rats, we examined the impact of pharmacological manipulation of the endocannabinoid system on sociability (i.e. social approach) and social novelty preference (which relies on social recognition). Control rats showed a clear preference for a "social" cage (i.e. unfamiliar stimulus rat placed under a wire mesh cage) versus an "empty" cage, and spent more time exploring a "novel" cage (i.e. new stimulus rat) versus a "familiar" cage. In contrast, rats receiving PCP (5 mg/kg, b.i.d. for 7 days, followed by a 7 day-washout period) showed intact sociability, but lacked social novelty preference. This PCP-induced deficit was due to increased activity at CB1 receptors as it was reversed by systemic administration of the CB1 antagonist AM251 (1 mg/kg). In agreement with this hypothesis, the cannabinoid agonist CP55,940 (0.003-0.03 mg/kg) dose-dependently suppressed social novelty preference in control animals without affecting sociability. Taken together, these data suggest that PCP-treated rats have a deficit in social cognition, possibly induced by increased stimulation of CB1 receptors. This deficit, however, is distinct from the social withdrawal previously observed in these animals, as the latter is due to deficient, rather than increased, CB1 stimulation. PMID:26706691

  8. Virus-induced airway hyperresponsiveness in the guinea-pig: possible involvement of histamine and inflammatory cells.

    PubMed Central

    Folkerts, G.; De Clerck, F.; Reijnart, I.; Span, P.; Nijkamp, F. P.

    1993-01-01

    histamine, twice a day (30 min) during 4 successive days, do not demonstrate an increased airway responsiveness, but instead show tachyphylaxis in response to histamine in vitro. In addition, no influx of inflammatory cells is found in these animals. 8. These results suggest that histamine does not directly increase the responsiveness of the guinea-pig trachea; however, histamine may be involved in a cascade of events leading to airway hyperresponsiveness after a viral infection, a process that could be related to an influx and/or an activation of broncho-alveolar cells after PI-3 virus stimulation. PMID:8097951

  9. Impairment of the mitochondrial respiratory chain activity in diethylnitrosamine-induced rat hepatomas: possible involvement of oxygen free radicals.

    PubMed

    Boitier, E; Merad-Boudia, M; Guguen-Guillouzo, C; Defer, N; Ceballos-Picot, I; Leroux, J P; Marsac, C

    1995-07-15

    Alterations in the energy metabolism of cancer cells have been reported for many years. However, the deleterious mechanisms involved in these deficiencies have not yet been clearly proved. The main goal of this study was to decipher the harmful mechanisms responsible for the respiratory chain deficiencies in the course of diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis, where mitochondrial DNA abnormalities had been previously reported. The respiratory activity of freshly isolated hepatoma mitochondria, assessed by oxygen consumption experiments and enzymatic assays, presented a severe complex I deficiency 19 months after DENA treatment, and later on, in addition, a defective complex III activity. Since respiratory complex subunits are encoded by both nuclear and mitochondrial genes, we checked whether the respiratory chain defects were due to impaired synthesis processes. The specific immunodetection of complex I failed to show any alterations in the steady-state levels of both nuclear and mitochondrial encoded subunits in the hepatomas. Moreover, in vitro protein synthesis experiments carried out on freshly isolated hepatoma mitochondria did not bring to light any modifications in the synthesis of the mitochondrial subunits of the respiratory complexes, whatever the degree of tumor progression. Finally, Southern blot analysis of mitochondrial DNA did not show any major mitochondrial DNA rearrangements in DENA-induced hepatomas. Because the synthetic processes of respiratory complexes did not seem to be implicated in the respiratory chain impairment, these deficiencies could be partly ascribed to a direct toxic impact of highly reactive molecules on these complexes, thus impairing their function. The mitochondrial respiratory chain is an important generator of noxious, reactive oxygen free radicals such as superoxide and H2O2, which are normally catabolized by powerful antioxidant scavengers. Nineteen months after DENA treatment, a general collapse of

  10. Possible involvement of hippocampal immediate-early genes in contextual fear memory deficit induced by cranial irradiation.

    PubMed

    Son, Yeonghoon; Kang, Sohi; Kim, Jinwook; Lee, Sueun; Kim, Jong-Choon; Kim, Sung-Ho; Kim, Joong-Sun; Jo, Sung-Kee; Jung, Uhee; Youn, BuHyun; Shin, Taekyun; Yang, Miyoung; Moon, Changjong

    2016-09-01

    Cranial irradiation can trigger adverse effects on brain functions, including cognitive ability. However, the cellular and molecular mechanisms underlying radiation-induced cognitive impairments remain still unknown. Immediate-early genes (IEGs) are implicated in neuronal plasticity and the related functions (i.e., memory formation) in the hippocampus. The present study quantitatively assessed changes in the mRNA and protein levels of the learning-induced IEGs, including Arc, c-fos, and zif268, in the mouse hippocampus after cranial irradiation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mice (male, 8-week-old C57BL/6) received whole-brain irradiation with 0 or 10Gy of gamma-ray and, 2weeks later, contextual fear conditioning (CFC) was used to induce IEGs. In the CFC task, mice evaluated 2weeks after irradiation exhibited significant memory deficits compared with sham (0Gy)-irradiated controls. The levels of mRNA encoding IEGs were significantly upregulated in the hippocampus 10 and 30min after CFC training. The mRNA levels in the irradiated hippocampi were significantly lower than those in the sham-irradiated controls. The IEG protein levels were significantly increased in all hippocampal regions, including the hippocampal dentate gyrus, cornu ammonis (CA)1, and CA3, after CFC training. The CFC-induced upregulation of Arc and c-fos in 10Gy-irradiated hippocampi was significantly lower than that in sham-irradiated controls, although there were no significant differences in the protein levels of the learning-induced zif268 between sham-irradiated and 10Gy-irradiated hippocampi. Thus, cranial irradiation with 10Gy of gamma-ray impairs the induction of hippocampal IEGs (particularly Arc and c-fos) via behavioral contextual fear memory, and this disturbance may be associated with the memory deficits evident in mice after cranial irradiation, possibly through the dysregulation of neuronal

  11. Correlation of the antimicrobial activity of salicylaldehydes with broadening of the NMR signal of the hydroxyl proton. Possible involvement of proton exchange processes in the antimicrobial activity.

    PubMed

    Elo, Hannu; Kuure, Matti; Pelttari, Eila

    2015-03-01

    Certain substituted salicylaldehydes are potent antibacterial and antifungal agents and some of them merit consideration as potential chemotherapeutic agents against Candida infections, but their mechanism of action has remained obscure. We report here a distinct correlation between broadening of the NMR signal of the hydroxyl proton of salicylaldehydes and their activity against several types of bacteria and fungi. When proton NMR spectra of the compounds were determined using hexadeuterodimethylsulfoxide as solvent and the height of the OH proton signal was measured, using the signal of the aldehyde proton as an internal standard, it was discovered that a prerequisite of potent antimicrobial activity is that the proton signal is either unobservable or relatively very low, i.e. that it is extremely broadened. Thus, none of the congeners whose OH proton signal was high were potent antimicrobial agents. Some congeners that gave a very low OH signal were, however, essentially inactive against the microbes, indicating that although drastic broadening of the OH signal appears to be a prerequisite, also other (so far unknown) factors are needed for high antimicrobial activity. Because broadening of the hydroxyl proton signal is related to the speed of the proton exchange process(es) involving that proton, proton exchange may be involved in the mechanism of action of the compounds. Further studies are needed to analyze the relative importance of different factors (such as electronic effects, strength of the internal hydrogen bond, co-planarity of the ring and the formyl group) that determine the rates of those processes. PMID:25621992

  12. A possible mechanism of action of danazol and an ethinylestradiol/norgestrel combination used as postcoital contraceptive agents.

    PubMed

    Rowlands, S; Kubba, A A; Guillebaud, J; Bounds, W

    1986-06-01

    Twenty-seven women requesting postcoital contraception were randomly allocated to take an ethinylestradiol/dl-norgestrel combination or danazol. Urine specimens were assayed for luteinising hormone (LH) and pregnanediol-3-glucuronide (P3G) levels from the day of the postcoital treatment to the next period. In addition, the urine samples of these recruits and 12 additional women were assayed for the Beta-subunit of human chorionic gonadotropin (B-hCG). A consistent pattern of alteration in urinary steroids was lacking, indicating a heterogeneous effect on ovarian function. There was no evidence of early pregnancy in successfully treated cases. We suggest that the main mechanism of action of these drugs is at the endometrial level. PMID:3533419

  13. [Possible mechanisms of the antitoxic action of calcium-containing derivatives of pantothenic acid in streptomycin poisoning].

    PubMed

    Dorofeev, B F; Chiger, V B; Moiseenok, A G

    1987-12-01

    Calcium salts of pantothenate (CPN), 4'-phosphopantothenate (CPP), S-sulfopantetheine (CSP), as well as pantetheine and panthenol were administered to mice by various routes and the influence of the administration route on acute toxicity of streptomycin (500 mg/kg, subcutaneously) was studied. It was shown that with subcutaneous, intramuscular, intraperitoneal and intravenous administration of CPN, CPP and CSP the acute toxicity of streptomycin was lower. The value of ED50 and the ranges of the antitoxic action (LD50/ED50) were indicative of high efficacy of CPP on its intravenous administration. In rats all the tested compounds normalized the liver excreting function (bromsulphalein test) impaired by exposure to streptomycin in subtoxic doses (200 mg/kg). The lowest levels of acetylation of the sulfacyl sodium test dose were observed in the animals treated with streptomycin in combination with CPN, CPP or CSP which could be explained by increased excretion and acetylation (detoxication) of the antibiotic. PMID:3439795

  14. A possible approach for setting a mercury risk-based action level based on tribal fish ingestion rates.

    PubMed

    Harper, Barbara L; Harris, Stuart G

    2008-05-01

    Risks from mercury and other contaminants in fish for a large Columbia River dataset are evaluated in this paper for a range of consumption rates. Extensive ethnohistorical, nutritional, recent ethnographic surveys, and other documentation was reviewed to confirm previous determinations that the traditional subsistence fish consumption rate is 500 pounds per capita annually, or 620 g per day (gpd). Lower comtemporary consumption rates for other population subsets are also discussed. The causes of the current suppression of fish consumption are discussed and the cultural, educational, social, and trade and economic impacts of the loss of fish are considered. Action levels for mercury for riverine Tribes in the Columbia Basin are suggested at 0.1 ppm or less based on the combined risk from mercury plus other contaminants, the higher fish consumption rates, the existing cultural deficit due to loss of salmon and other stressors, the health benefits of fish, and the cultural and economic importance of fish. The goal of fish advisories is to reduce fish consumption even further, which shifts the burden of avoiding risk to the very people who already bear the burdens of contaminant exposure, socio-economic impacts and cultural loss. However, because Tribal communities often do not have the choice of giving up more food, income, religion, culture, and heritage in order to avoid contamination, they are forced into choosing between culture and health. Many tribal members choose to incur chemical risk rather than giving up their culture and religion. We believe that lowering the action level for mercury is part of the federal fiduciary responsibility to American Indian Tribes. PMID:17631290

  15. Action selection in a possible model of striatal medium spiny neuron dysfunction: behavioral and EEG data in a patient with benign hereditary chorea.

    PubMed

    Beste, Christian; Saft, Carsten

    2015-01-01

    Chaining or cascading of different actions and responses is necessary to accomplish a goal. Yet, little is known about the functional neuroanatomical-electrophysiological mechanisms mediating these processes. Computational models suggest that medium spiny neurons (MSNs) play an important role in action cascading, but this assumption has hardly been tested relating neuroanatomical and electrophysiological parameters in a human model of circumscribed MSN dysfunction. As a possible human model of circumscribed MSN dysfunction, we investigate benign hereditary chorea in a case-control study applying bootstrap statistics. To investigate these mechanisms, we used a stop-change paradigm, where we apply mathematical constraints to describe the degree of how task goals are activated with more or less overlap during action cascading. We record event-related potentials and analyze neural synchronization processes. The results show that MSN dysfunctions lead to deficits in action cascading processes only when two response options seek simultaneous access to response selection resources. Attentional selection processes are not affected, but processes reflecting the transition between stimulus evaluation and responding are affected. The results underline computational models of MSN functioning and show that dysfunction in these networks leads to a more parallel and hence inefficient response selection. PMID:24135770

  16. Action at an Attentional Distance: A Study of Children's Reasoning about Causes and Effects Involving Spatial and Attentional Discontinuity

    ERIC Educational Resources Information Center

    Grotzer, Tina A.; Solis, S. Lynneth

    2015-01-01

    Spatial discontinuity between causes and effects is a feature of many scientific concepts, particularly those in the environmental and ecological sciences. Causes can be spatially separated from their effects by great distances. Action at a distance, the idea that causes and effects can be separated in physical space, is a well-studied concept in…

  17. Parents as Co-Researchers: A Participatory Action Research Initiative Involving Parents of People with Intellectual Disabilities in Ireland

    ERIC Educational Resources Information Center

    Walmsley, Jan; Mannan, Hasheem

    2009-01-01

    This paper evaluates a participatory action research (PAR) approach to conducting family research in Ireland. Drawing on PAR methodology it describes how parents of people with intellectual disabilities were recruited and trained to facilitate focus groups of parents in Ireland, in order to create an evidence base to support improved dialogue…

  18. SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson

    PubMed Central

    Santos, Gesivaldo; Giraldez-Alvarez, Lisandro Diego; Ávila-Rodriguez, Marco; Capani, Francisco; Galembeck, Eduardo; Neto, Aristóteles Gôes; Barreto, George E.; Andrade, Bruno

    2016-01-01

    Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection. PMID:27199743

  19. SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson.

    PubMed

    Santos, Gesivaldo; Giraldez-Alvarez, Lisandro Diego; Ávila-Rodriguez, Marco; Capani, Francisco; Galembeck, Eduardo; Neto, Aristóteles Gôes; Barreto, George E; Andrade, Bruno

    2016-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection. PMID:27199743

  20. Ground-water flow and the possible effects of remedial actions at J-Field, Aberdeen Proving Ground, Maryland

    USGS Publications Warehouse

    Hughes, W.B.

    1995-01-01

    J-Field, located in the Edgewood Area of Aberdeen Proving Ground, Md, has been used since World War II to test and dispose of explosives, chemical warfare agents, and industrial chemicals resulting in ground-water, surface-water, and soil contami- nation. The U.S. Geological Survey finite-difference model was used to better understand ground-water flow at the site and to simulate the effects of remedial actions. A surficial aquifer and a confined aquifer were simulated with the model. A confining unit separates these units and is represented by leakance between the layers. The area modeled is 3.65 mi2; the model was constructed with a variably spaced 40 X 38 grid. The horizontal and lower boundaries of the model are all no-flow boundaries. Steady-state conditions were used. Ground water at the areas under investigation flows from disposal pit areas toward discharge areas in adjacent estuaries or wetlands. Simulations indicate that capping disposal areas with an impermeable cover effectively slows advective ground water flow by 0.7 to 0.5 times. Barriers to lateral ground-water flow were simulated and effectively prevented the movement of ground water toward discharge areas. Extraction wells were simulated as a way to contain ground-water contamination and to extract ground water for treatment. Two wells pumping 5 gallons per minute each at the toxic-materials disposal area and a single well pumping 2.5 gallons per minute at the riot-control-agent disposal area effectively contained contamination at these sites. A combi- nation of barriers to horizontal flow east and south of the toxic-materials disposal area, and a single extraction well pumping at 5 gallons per minute can extract contaminated ground water and prevent pumpage of marsh water.

  1. Erythropoiesis-stimulating agent slows the progression of chronic kidney disease: a possibility of a direct action of erythropoietin.

    PubMed

    Tsuruya, Kazuhiko; Yoshida, Hisako; Suehiro, Takaichi; Fujisaki, Kiichiro; Masutani, Kosuke; Kitazono, Takanari

    2016-04-01

    Background Controversy exists regarding the renoprotective effect of erythropoiesis-stimulating agent (ESA) in progressive chronic kidney disease (CKD) with renal anemia. In this study, we examined whether ESA therapy has a renoprotective effect in progressive CKD. Methods The subjects in this retrospective observational study were 68 non-dialysis dependent CKD patients with renal anemia. We compared the progression rate (PR), defined by the slope of the linear regression line of estimated glomerular filtration rate, measured during 6 months just before and after the start of ESA therapy. We also investigated the factors affecting renoprotective efficacy of ESA therapy against the progression of CKD. Results Median (interquartile range) PR decreased significantly from 6.2 (3.7-12.7) to 4.0 (-0.3 to 7.3) mL/min/1.73 m(2)/year after the start of ESA therapy. Blood pressure levels and rate of medication with renin-angiotensin system inhibitors were comparable between the two periods. Next, we investigated the factors affecting renoprotective efficacy of ESA therapy against the progression of CKD. Thirty patients were good renal responders, defined as those with the ratio of post-/pre-PR of <0.5 and the difference of pre- minus post-PR >5.0 mL/min/1.73 m(2)/year, and 38 patients were poor renal responders who did not meet the definition of good renal responders. Multivariable logistic regression analysis showed that weekly ESA dose, but not increase in hemoglobin level, was a significant and independent determinant of the renoprotective effect of ESA. Conclusion ESA therapy slows the progression of CKD and part of the effect might be attributed to the direct renoprotective action of ESA. PMID:26822074

  2. Assessment of possible carcinogenicity of oxyfluorfen to humans using mode of action analysis of rodent liver effects.

    PubMed

    Stagg, Nicola J; LeBaron, Matthew J; Eisenbrandt, David L; Gollapudi, B Bhaskar; Klaunig, James E

    2012-08-01

    Oxyfluorfen is a herbicide that is not genotoxic and produces liver toxicity in rodents, following repeated administration at high dose levels. Lifetime rodent feeding studies reported in 1977 with low-purity oxyfluorfen (85%) showed no increase in any tumor type in rats (800 ppm, high dose) and only a marginally increased incidence of hepatocellular tumors in male CD-1 mice at the highest dose (200 ppm). To evaluate the potential carcinogenicity of the currently registered oxyfluorfen (> 98% purity), we conducted a series of short-term liver mode of action (MOA) toxicology studies in male CD-1 mice administered dietary doses of 0, 40, 200, 800, and 1600 ppm for durations of 3, 7, 10, or 28 days. MOA endpoints examined included liver weight, histopathology, cell proliferation, nuclear receptor-mediated gene expression, and other peroxisome proliferator-specific endpoints and their reversibility. Minimal liver effects were observed in mice administered doses at or below 200 ppm for up to 28 days. Increased liver weight, single-cell necrosis, cell proliferation, and peroxisomal acyl-CoA oxidase (ACO) were observed at 800 ppm after 28 days, but there was no increase in peroxisomes. Expression of Cyp2b10 and Cyp4a10 transcripts, markers of constitutive androstane receptor and peroxisome proliferator activated receptor α nuclear receptor activation, respectively, were increased at 800 and 1600 ppm after 3 or 10 days. Collectively, these data along with the negative genotoxicity demonstrate that oxyfluorfen (> 98% purity) has the potential to induce mouse liver tumors through a nongenotoxic, mitogenic MOA with a clear threshold and is not predicted to be carcinogenic in humans at relevant exposure levels. PMID:22539621

  3. Involvement of adrenoceptors, dopamine receptors and AMPA receptors in antidepressant-like action of 7-O-ethylfangchinoline in mice

    PubMed Central

    Sheng, Zhao-fu; Cui, Xiang-yu; Cui, Su-ying; Yu, Bin; Zhang, Xue-qiong; Li, Sheng-jie; Cao, Qing; Huang, Yuan-li; Xu, Ya-ping; Song, Jin-zhi; Ding, Hui; Lin, Zhi-ge; Yang, Guang; Zhang, Yong-he

    2015-01-01

    Aim: 7-O-ethylfangchinoline (YH-200) is a bisbenzylisoquinoline derivative. The aim of this study was to investigate the antidepressant-like action and underlying mechanisms of YH-200 in mice. Methods: Mice were treated with YH-200 (15, 30, and 60 mg/kg, ig) or tetrandrine (30 and 60 mg/kg, ig) before conducting forced swimming test (FST), tail suspension test (TST), or open field test (OFT). Results: YH-200 (60 mg/kg) significantly decreased the immobility time in both FST and TST, and prolonged the latency to immobility in FST. YH-200 (60 mg/kg) was more potent than the natural bisbenzylisoquinoline alkaloid tetrandrine (60 mg/kg) in FST. Pretreatment with α1-adrenoceptor antagonist prazosin (1 mg/kg), β-adrenoceptor antagonist propranolol (2 mg/kg), dopamine D1/D5 receptor antagonist SCH23390 (0.05 mg/kg), dopamine D2/D3 receptor antagonist haloperidol (0.2 mg/kg) or AMPA receptor antagonist NBQX (10 mg/kg) prevented the antidepressant-like action of YH-200 (60 mg/kg) in FST. In contrast, pretreatment with α2 adrenoceptor antagonist yohimbine (1 mg/kg) augmented the antidepressant-like action of YH-200 (30 mg/kg) in FST. Chronic administration of YH-200 (30 and 60 mg/kg for 14 d) did not produce drug tolerance; instead its antidepressant-like action was strengthened. Chronic administration of YH-200 did not affect the body weight of mice compared to control mice. Conclusion: YH-200 exerts its antidepressant-like action in mice via acting at multi-targets, including α1, α2 and β-adrenoceptors, D1/D5 and D2 /D3 receptors, as well as AMPA receptors. PMID:26238289

  4. The Actions of Headmasters and Headmistresses in Fostering Parent & Family Involvement in Low-Income Schools in Tamil Nadu, India

    ERIC Educational Resources Information Center

    Shekar, Anupama

    2013-01-01

    Decades of research has examined the contribution of parent involvement to children's educational outcomes. Research has also attempted to identify meaningful involvement practices, taking place at home or in school and, as a result, measuring its effects on school, school staff and parents themselves. Despite the extensive research base, very…

  5. Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses

    PubMed Central

    Ngan, Luong Thi My; Jang, Myeong Jin; Kwon, Min Jung; Ahn, Young Joon

    2015-01-01

    Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3–>8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV. PMID:25860871

  6. Prokinetic Activity of Prunus persica (L.) Batsch Flowers Extract and Its Possible Mechanism of Action in Rats

    PubMed Central

    Han, Wei; Xu, Jing Dong; Wei, Feng Xian; Zheng, Yong Dong; Ma, Jian Zhong; Xu, Xiao Dong; Wei, Zhen Gang; Wang, Wen; Zhang, You Cheng

    2015-01-01

    The peach tree, Prunus persica (L.) Batsch, is widely cultivated in China, and its flowers have been used for centuries in traditional Chinese medicine to treat gut motility disorders. But few studies have explored the pharmacological effect of Prunus persica (L.) Batsch flowers on gastrointestinal motility. In this study, the activities of different extracts from Prunus persica (L.) Batsch flowers on the smooth muscle contractions were evaluated using isolated colon model, and the ethyl acetate extract (EAE) showed the strongest effects in vitro. EAE (10−8–10−5 g/mL) caused a concentration-dependent stimulatory effect in rat colonic tissue. Additionally, ketotifen (100 µM), cimetidine (10 µM), and pyrilamine (1 µM) produced a significant inhibition of contractions caused by EAE. Furthermore, immunofluorescence and toluidine blue staining revealed increased numbers of mast cells in the EAE group, and EAE increased histamine release from the colonic tissues. These data indicate that EAE has significant prokinetic activity and acts by a mechanism that mainly involves mast cell degranulation. Our study provides a pharmacological basis for the use of an extract of Prunus persica (L.) Batsch flowers in the treatment of gut motility disorders. PMID:25821812

  7. Choosing Actions

    PubMed Central

    Rosenbaum, David A.; Chapman, Kate M.; Coelho, Chase J.; Gong, Lanyun; Studenka, Breanna E.

    2013-01-01

    Actions that are chosen have properties that distinguish them from actions that are not. Of the nearly infinite possible actions that can achieve any given task, many of the unchosen actions are irrelevant, incorrect, or inappropriate. Others are relevant, correct, or appropriate but are disfavored for other reasons. Our research focuses on the question of what distinguishes actions that are chosen from actions that are possible but are not. We review studies that use simple preference methods to identify factors that contribute to action choices, especially for object-manipulation tasks. We can determine which factors are especially important through simple behavioral experiments. PMID:23761769

  8. Understanding Obesity Perceptions in America: An Exploratory Study of Public Perceptions of the Problem and Possible Actions for Health Product Marketers.

    PubMed

    Emmett, Dennis; Chandra, Ashish

    2015-01-01

    Many healthcare professionals have stated that obesity is a major problem in the United States. The rate of obesity in young people has been rising until just recently, when it was reported to have leveled off. The authors examine the problem in terms of people's perception of how great a problem it is, along with examining their perception of the causes and possible remedies for the problem. If the general population does not believe that a problem exists, then corrective action will be hampered. Then, the authors examine what impact this has on marketing products to address this problem. PMID:26684682

  9. Factors associated with regulatory action involving investigation of illnesses associated with Shiga toxin-producing Escherichia coli in products regulated by the Food Safety and Inspection Service.

    PubMed

    Green, Alice L; Seys, Scott; Douris, Aphrodite; Levine, Jeoff; Robertson, Kis

    2014-07-01

    We described characteristics of the Escherichia coli O157 and Escherichia coli non-O157 illness investigations conducted by the United States Department of Agriculture's Food Safety and Inspection Service (FSIS) during the 5-year period from 2006 through 2010. We created a multivariable logistic regression model to determine characteristics of these investigations that were associated with FSIS regulatory action, which was defined as having occurred if a product recall occurred or if FSIS personnel performed an environmental health assessment (Food Safety Assessment) at the implicated establishment. During this period, FSIS took regulatory action in 38 of 88 (43%) investigations. Illness investigations in which FoodNet states were involved were more likely to result in regulatory action. Illness investigations in which state and local traceback, or FSIS traceback occurred were more likely to result in regulatory action. Reasons for lack of action included evidence of cross-contamination after the product left a regulated establishment, delayed notification, lack of epidemiological information, and insufficient product information. PMID:24826872

  10. Is Earth F**ked? Dynamical Futility of Global Environmental Management and Possibilities for Sustainability via Direct Action Activism

    NASA Astrophysics Data System (ADS)

    wErnEr, B.

    2012-12-01

    Environmental challenges are dynamically generated within the dominant global culture principally by the mismatch between short-time-scale market and political forces driving resource extraction/use and longer-time-scale accommodations of the Earth system to these changes. Increasing resource demand is leading to the development of two-way, nonlinear interactions between human societies and environmental systems that are becoming global in extent, either through globalized markets and other institutions or through coupling to global environmental systems such as climate. These trends are further intensified by dissipation-reducing technological advances in transactions, communication and transport, which suppress emergence of longer-time-scale economic and political levels of description and facilitate long-distance connections, and by predictive environmental modeling, which strengthens human connections to a short-time-scale virtual Earth, and weakens connections to the longer time scales of the actual Earth. Environmental management seeks to steer fast scale economic and political interests of a coupled human-environmental system towards longer-time-scale consideration of benefits and costs by operating within the confines of the dominant culture using a linear, engineering-type connection to the system. Perhaps as evidenced by widespread inability to meaningfully address such global environmental challenges as climate change and soil degradation, nonlinear connections reduce the ability of managers to operate outside coupled human-environmental systems, decreasing their effectiveness in steering towards sustainable interactions and resulting in managers slaved to short-to-intermediate-term interests. In sum, the dynamics of the global coupled human-environmental system within the dominant culture precludes management for stable, sustainable pathways and promotes instability. Environmental direct action, resistance taken from outside the dominant culture, as in

  11. Gene expression profiles following exposure to a developmental neurotoxicant, Aroclor 1254: Pathway analysis for possible mode(s) of action

    SciTech Connect

    Royland, Joyce E.; Kodavanti, Prasada Rao S.

    2008-09-01

    Epidemiological studies indicate that low levels of polychlorinated biphenyl (PCB) exposure can adversely affect neurocognitive development. In animal models, perturbations in calcium signaling, neurotransmitters, and thyroid hormones have been postulated as potential mechanisms for PCB-induced developmental neurotoxicity. In order to understand the role of these proposed mechanisms and to identify other mechanisms in PCB-induced neurotoxicity, we have chosen a global approach utilizing oligonucleotide microarrays to examine gene expression profiles in the brain following developmental exposure to Aroclor 1254 (0 or 6 mg/kg/day from gestation day 6 through postnatal day (PND) 21) in Long-Evans rats. Gene expression levels in the cerebellum and hippocampus from PNDs 7 and 14 animals were determined on Affymetrix rat 230A{sub 2}.0 chips. In the cerebellum, 87 transcripts were altered at PND7 compared to 27 transcripts at PND14 by Aroclor 1254 exposure, with only one transcript affected at both ages. In hippocampus, 175 transcripts and 50 transcripts were altered at PND7 and PND14, respectively, by Aroclor 1254 exposure with five genes commonly affected. Functional analysis suggests that pathways related to calcium homeostasis (Gng3, Ryr2, Trdn, Cacna1a), intracellular signaling (Camk2d, Stk17b, Pacsin2, Ryr2, Trio, Fert2, Ptk2b), axonal guidance (Lum, Mxd3, Akap11, Gucy1b3), aryl hydrocarbon receptor signaling (Nfia, Col1a2), and transcripts involved in cell proliferation (Gspt2, Cdkn1c, Ptk2b) and differentiation (Ifitm31, Hpca, Zfp260, Igsf4a, Hes5) leading to the development of nervous system were significantly altered by Aroclor 1254 exposure. Of the two brain regions examined, Aroclor 1254-induced genomic changes were greater in the hippocampus than the cerebellum. The genomic data suggests that PCB-induced neurotoxic effects were due to disruption of normal ontogenetic pattern of nervous system growth and development by altering intracellular signaling pathways

  12. Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction

    PubMed Central

    Ait‐Belgnaoui, A; Han, W; Lamine, F; Eutamene, H; Fioramonti, J; Bueno, L; Theodorou, V

    2006-01-01

    Background Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti‐inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p‐MLC). Methods Female Wistar rats received either 1011 CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham‐PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham‐PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p‐MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham‐PRS. Results PRS significantly increased the number of spike bursts for CRD pressures of 30–60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p‐MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase. Conclusion L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic. PMID:16507583

  13. The possible involvement of copper-containing nitrite reductase (NirK) and flavohemoglobin in denitrification by the fungus Cylindrocarpon tonkinense.

    PubMed

    Kim, Sang-Wan; Fushinobu, Shinya; Zhou, Shengmin; Wakagi, Takayoshi; Shoun, Hirofumi

    2010-01-01

    The occurrence of denitrification and nitrate respiration among eukaryotes has been established during the last few decades. However, denitrification-related eukaryotic genes have been isolated from only a few fungi, and eukaryotic denitrification (or nitrate respiration) is still inadequately understood. In this study, we identified genes that were up-regulated under denitrifying conditions in the fungus Cylindrocarpon tonkinense using the suppression subtraction hybridization technique, and the expression patterns of these genes were characterized by Northern analysis. We identified copper-containing nitrite reductase, cytochrome P450 nitric oxide reductase, flavohemoglobin (Fhb), and formate/nitrite transporter homolog genes as possibly involved in fungal denitrification. Our results concerning the involvement of Fhb and formate/nitrite transporter perhaps provide new insight into the fungal denitrification system. PMID:20622453

  14. The anticonvulsant action of the galanin receptor agonist NAX-5055 involves modulation of both excitatory- and inhibitory neurotransmission.

    PubMed

    Walls, Anne B; Flynn, Sean P; West, Peter J; Müller, Margit S; Bak, Lasse K; Bulaj, Grzegorz; Schousboe, Arne; White, H Steve

    2016-03-01

    The endogenous neuropeptide galanin is ubiquitously expressed throughout the mammalian brain. Through the galanin receptors GalR1-3, galanin has been demonstrated to modulate both glutamatergic and GABAergic neurotransmission, and this appears to be important in epilepsy and seizure activity. Accordingly, galanin analogues are likely to provide a new approach to seizure management. However, since peptides are generally poor candidates for therapeutic agents due to their poor metabolic stability and low brain bioavailability, a search for alternative strategies for the development of galanin-based anti-convulsant drugs was prompted. Based on this, a rationally designed GalR1 preferring galanin analogue, NAX-5055, was synthesized. This compound demonstrates anti-convulsant actions in several animal models of epilepsy. However, the alterations at the cellular level leading to this anti-convulsant action of NAX-5055 are not known. Here we investigate the action of NAX-5055 at the cellular level by determining its effects on excitatory and inhibitory neurotransmission, i.e. vesicular release of glutamate and GABA, respectively, in cerebellar, neocortical and hippocampal preparations. In addition, its effects on cell viability and neurotransmitter transporter capacity were examined to evaluate potential cell toxicity mediated by NAX-5055. It was found that vesicular release of glutamate was reduced concentration-dependently by NAX-5055 in the range from 0.1 to 1000 nM. Moreover, exposure to 1 μM NAX-5055 led to a reduction in the extracellular level of glutamate and an elevation of the extracellular level of GABA. Altogether these findings may at least partly explain the anti-convulsant effect of NAX-5055 observed in vivo. PMID:26894875

  15. Antifungal Action of Methylene Blue Involves Mitochondrial Dysfunction and Disruption of Redox and Membrane Homeostasis in C. albicans.

    PubMed

    Ansari, Moiz A; Fatima, Zeeshan; Hameed, Saif

    2016-01-01

    Candida albicans is known to cause infections ranging from superficial and systemic in immunocompromised person. In this study, we explored that the antifungal action of Methylene blue (MB) is mediated through mitochondrial dysfunction and disruption of redox and membrane homeostasis against C. albicans. We demonstrated that MB displayed its antifungal potential against C. albicans and two clinical isolates tested. We also showed that MB is effective against two non- albicans species as well. Notably, the antifungal effect of MB seems to be independent of the major drug efflux pumps transporter activity. We explored that MB treated Candida cells were sensitive on non-fermentable carbon source leading us to propose that MB inhibits mitochondria. This sensitive phenotype was reinforced with the fact that sensitivity of Candida cells to MB could be rescued upon the supplementation of ascorbic acid, an antioxidant. This clearly suggests that disturbances in redox status are linked with MB action. We further demonstrated that Candida cells were susceptible to membrane perturbing agent viz. SDS which was additionally confirmed by transmission electron micrographs showing disruption of membrane integrity. Moreover, the ergosterol levels were significantly decreased by 66% suggesting lipid compositional changes due to MB. Furthermore, we could demonstrate that MB inhibits the yeast to hyphal transition in C. albicans which is one of the major virulence attribute in most of the hyphal inducing conditions. Taken together, the data generated from present study clearly establishes MB as promising antifungal agent that could be efficiently employed in strategies to treat Candida infections. PMID:27006725

  16. Cordycepin Decreases Compound Action Potential Conduction of Frog Sciatic Nerve In Vitro Involving Ca (2+) -Dependent Mechanisms.

    PubMed

    Yao, Li-Hua; Yu, Hui-Min; Xiong, Qiu-Ping; Sun, Wei; Xu, Yan-Liang; Meng, Wei; Li, Yu-Ping; Liu, Xin-Ping; Yuan, Chun-Hua

    2015-01-01

    Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP), which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 ± 8.06% and 57.34% ± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca(2+)-free medium or in the presence of Ca(2+) channel blockers (CdCl2/LaCl3). Pretreatment with L-type Ca(2+) channel antagonist (nifedipine/deltiazem) also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca(2+) channel antagonists (Ni(2+)) failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca(2+) channel-dependent mechanism. PMID:26078886

  17. Histamine H1 receptor involvement in prepulse inhibition and memory function: Relevance for the antipsychotic actions of clozapine

    PubMed Central

    Roegge, Cindy S.; Perraut, Charles; Hao, Xin; Levin, Edward D.

    2009-01-01

    Histamine H1 blockade is one of the more prominent actions of the multi-receptor acting antipsychotic clozapine. It is currently not known how much this H1 antagonism of clozapine contributes to the therapeutic or adverse side effects of clozapine. The current studies with Sprague-Dawley rats were conducted to determine the participation of histaminergic H1 receptor subtype in sensorimotor plasticity and memory function affected by clozapine using tests of prepulse inhibition (PPI) and radial-arm maze choice accuracy. The PPI impairment caused by the glutamate antagonist dizocilpine (MK-801) was significantly attenuated by clozapine. In the current project, we found that the selective H1 antagonist pyrilamine also reversed the dizocilpine-induced impairment in PPI of tactile startle with an auditory prepulse. In the radial-arm maze (RAM), pyrilamine, like clozapine, impaired working memory and caused a significant dose-related slowing of response. Pyrilamine, however, decreased the number of reference memory errors. We have previously shown that nicotine effectively attenuates the clozapine-induced working memory impairment, but in the current study, nicotine did not significantly alter the effects of pyrilamine on the RAM. In summary, the therapeutic effect of clozapine in reversing PPI impairment was mimicked by the H1 antagonist pyrilamine, while pyrilamine had a mixed effect on cognition. Pyrilamine impaired working memory but improved reference memory in rats. Thus, H1 antagonism seems to play a role in part of the beneficial actions of antipsychotics, such as clozapine. PMID:17382376

  18. Antifungal Action of Methylene Blue Involves Mitochondrial Dysfunction and Disruption of Redox and Membrane Homeostasis in C. albicans

    PubMed Central

    Ansari, Moiz A.; Fatima, Zeeshan; Hameed, Saif

    2016-01-01

    Candida albicans is known to cause infections ranging from superficial and systemic in immunocompromised person. In this study, we explored that the antifungal action of Methylene blue (MB) is mediated through mitochondrial dysfunction and disruption of redox and membrane homeostasis against C. albicans. We demonstrated that MB displayed its antifungal potential against C. albicans and two clinical isolates tested. We also showed that MB is effective against two non- albicans species as well. Notably, the antifungal effect of MB seems to be independent of the major drug efflux pumps transporter activity. We explored that MB treated Candida cells were sensitive on non-fermentable carbon source leading us to propose that MB inhibits mitochondria. This sensitive phenotype was reinforced with the fact that sensitivity of Candida cells to MB could be rescued upon the supplementation of ascorbic acid, an antioxidant. This clearly suggests that disturbances in redox status are linked with MB action. We further demonstrated that Candida cells were susceptible to membrane perturbing agent viz. SDS which was additionally confirmed by transmission electron micrographs showing disruption of membrane integrity. Moreover, the ergosterol levels were significantly decreased by 66% suggesting lipid compositional changes due to MB. Furthermore, we could demonstrate that MB inhibits the yeast to hyphal transition in C. albicans which is one of the major virulence attribute in most of the hyphal inducing conditions. Taken together, the data generated from present study clearly establishes MB as promising antifungal agent that could be efficiently employed in strategies to treat Candida infections. PMID:27006725

  19. Where the Action Is; A Log of Successful Urban Programs Involving Businessmen, Chambers of Commerce or Associations.

    ERIC Educational Resources Information Center

    Chamber of Commerce of the United States, Washington, DC.

    This log cites about 150 successful programs, dealing with key urban problems, which involve businessmen either individually or through efforts of their companies, chambers of commerce, and trade and professional associations. The examples are listed alphabetically by location by city or state name for statewide programs. A few national programs…

  20. Labor and Career Education: Ideas for Action. Handbook of Ideas for Involving and Integrating Labor in Career Education.

    ERIC Educational Resources Information Center

    Topougis, Nicholas J.

    This handbook provides specific examples of activities and procedures of labor-education collaboration within the context of the career education program. It is intended to help interested communities develop or expand labor's active involvement in the educational process. After an introduction, a section lists a number of concerns shared by…

  1. Expression of E-Cadherin and N-Cadherin in Perinatal Hamster Ovary: Possible Involvement in Primordial Follicle Formation and Regulation by Follicle-Stimulating Hormone

    PubMed Central

    Wang, Cheng; Roy, Shyamal K.

    2010-01-01

    We examined the expression and hormonal regulation of E-cadherin (CDH1) and N-cadherin (CDH2) with respect to primordial follicle formation. Hamster Cdh1 and Cdh2 cDNA and amino acid sequences were more than 90% similar to those of the mouse, rat, and human. Although CDH1 expression remained exclusively in the oocytes during neonatal ovary development, CDH2 expression shifted from the oocytes to granulosa cells of primordial follicles on postnatal day (P)8. Subsequently, strong CDH2 expression was restricted to granulosa cells of growing follicles. Cdh2 mRNA levels in the ovary decreased from embryonic d 13 through P10 with a transient increase on P7, which was the day before the appearance of primordial follicles. Cdh1 mRNA levels decreased from embryonic d 13 through P3 and then showed a transient increase on P8, coinciding with the formation of primordial follicles. CDH1 and CDH2 expression were consistent with that of mRNA. Neutralization of FSH in utero impaired primordial follicle formation with an associated decrease in Cdh2 mRNA and CDH2, but an increase in Cdh1 mRNA and CDH1 expression. The altered expression was reversed by equine chorionic gonadotropin treatment on P1. Whereas a CDH2 antibody significantly reduced the formation of primordial and primary follicles in vitro, a CDH1 antibody had the opposite effect. This is the first evidence to suggest that primordial follicle formation requires a differential spatiotemporal expression and action of CDH1 and CDH2. Further, FSH regulation of primordial follicle formation may involve the action of CDH1 and CDH2. PMID:20219978

  2. Involvement of G Protein-Coupled Receptor 30 (GPR30) in Rapid Action of Estrogen in Primate LHRH Neurons

    PubMed Central

    Noel, Sekoni D.; Keen, Kim L.; Baumann, David I.; Filardo, Edward J.; Terasawa, Ei

    2009-01-01

    Previously, we have reported that 17β-estradiol (E2) induces an increase in firing activity of primate LH-releasing hormone (LHRH) neurons. The present study investigates whether E2 alters LHRH release as well as the pattern of intracellular calcium ([Ca2+]i) oscillations and whether G protein-coupled receptor 30 (GPR30) plays a role in mediating the rapid E2 action in primate LHRH neurons. Results are summarized: 1) E2, the nuclear membrane-impermeable estrogen, estrogen-dendrimer conjugate, and the plasma membrane-impermeable estrogen, E2-BSA conjugate, all stimulated LHRH release within 10 min of exposure; 2) whereas the estrogen receptor antagonist, ICI 182,780, did not block the E2-induced LHRH release, E2 application to cells treated with pertussis toxin failed to induce LHRH release; 3) GPR30 mRNA was expressed in olfactory placode cultures, and GPR30 protein was expressed in a subset of LHRH neurons; 4) pertussis toxin treatment blocked the E2-induced increase in [Ca2+]i oscillations; 5) knockdown of GPR30 in primate LHRH neurons by transfection with small interfering RNA (siRNA) for GPR30 completely abrogated the E2-induced changes in [Ca2+]i oscillations, whereas transfection with control siRNA did not; 6) the estrogen-dendrimer conjugate-induced increase in [Ca2+]i oscillations also did not occur in LHRH neurons transfected with GPR30 siRNA; and 7) G1, a GPR30 agonist, resulted in changes in [Ca2+]i oscillations, similar to those observed with E2. Collectively, E2 induces a rapid excitatory effect on primate LHRH neurons, and this rapid action of E2 appears to be mediated, in part, through GPR30. PMID:19131510

  3. The involvement of neuronal nitric oxide synthase in antiepileptic action of alpha-asarone on pentylenetetrazol molding rats.

    PubMed

    Su, Jing; Zhu, Wenting; Liu, Jing; Yin, Jian; Qin, Wei; Jiang, Changbin

    2014-01-01

    The aim of the present study was to research the role of nitric oxide (NO) as a mediator of alpha (α)-asarone effect at the pentylenetetrazol (PTZ)-induced epileptiform discharge in rat. α-Asarone that was injected intraperitoneally twenty minutes before PTZ injection suppressed the clonic discharge effectively and the significant actions lasted for 30 min with no change of clonic amplitude. Administration of α-asarone did not influence interictal discharge. Four kinds of NO regulators were administered, including non-selective NG-nitro-L-arginine methyl ester (L-NAME), selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG) and NO substrate, L-arginine (ARG) and their influence on the actions of α-asarone were studied, and all of the regulators were administered fifteen minutes before α-asarone injection. L-NAME and 7-NI reversed the anticlonic activity of α-asarone, and a significant increase of clonic activity was induced by L-NAME later in L-NAME +.α-asarone + PTZ group. There were no significant differences between AG + α-asarone + PTZ and α-asarone + PTZ group. L-ARG played a dual role in this study. It aggravated clonic discharge in the early stage but relieved interictal discharge in the late stage compared with PTZ group alone, and the beneficial effect of α-asarone was also reversed. All the above results suggest that nNOS/NO pathway mediates the anticonvulsant effect of α-asarone, and NO played a biphasic role in PTZ modeling process, while iNOS was unrelated to the inhibition effect of α-asarone on PTZ induced epileptiform activity. PMID:25227079

  4. Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions

    PubMed Central

    Herz, Josephine; Reitmeir, Raluca; Hagen, Sabine I.; Reinboth, Barbara S.; Guo, Zeyun; Zechariah, Anil; ElAli, Ayman; Doeppner, Thorsten R.; Bacigaluppi, Marco; Pluchino, Stefano; Kilic, Ülkan; Kilic, Ertugrul; Hermann, Dirk M.

    2015-01-01

    Vascular endothelial growth factor (VEGF) has potent angiogenic and neuroprotective effects in the ischemic brain. Its effect on axonal plasticity and neurological recovery in the post-acute stroke phase was unknown. Using behavioral tests combined with anterograde tract tracing studies and with immunohistochemical and molecular biological experiments, we examined effects of a delayed i.c.v. delivery of recombinant human VEGF165, starting 3 days after stroke, on functional neurological recovery, corticorubral plasticity and inflammatory brain responses in mice submitted to 30 min of middle cerebral artery occlusion. We herein show that the slowly progressive functional improvements of motor grip strength and coordination, which are induced by VEGF, are accompanied by enhanced sprouting of contralesional corticorubral fibres that branched off the pyramidal tract in order to cross the midline and innervate the ipsilesional parvocellular red nucleus. Infiltrates of CD45+ leukocytes were noticed in the ischemic striatum of vehicle-treated mice that closely corresponded to areas exhibiting Iba-1+ activated microglia. VEGF attenuated the CD45+ leukocyte infiltrates at 14 but not 30 days post ischemia and diminished the microglial activation. Notably, the VEGF-induced anti-inflammatory effect of VEGF was associated with a downregulation of a broad set of inflammatory cytokines and chemokines in both brain hemispheres. These data suggest a link between VEGF’s immunosuppressive and plasticity-promoting actions that may be important for successful brain remodeling. Accordingly, growth factors with anti-inflammatory action may be promising therapeutics in the post-acute stroke phase. PMID:22198574

  5. Anti-neuroinflammatory properties of synthetic cryptolepine in human neuroblastoma cells: possible involvement of NF-κB and p38 MAPK inhibition.

    PubMed

    Olajide, Olumayokun A; Bhatia, Harsharan S; de Oliveira, Antonio C P; Wright, Colin W; Fiebich, Bernd L

    2013-05-01

    Cryptolepis sanguinolenta and its bioactive alkaloid, cryptolepine have shown anti-inflammatory activity. However, the underlying mechanism of anti-inflammatory action in neuronal cells has not been investigated. In the present study we evaluated an extract of C. sanguinolenta (CSE) and cryptolepine (CAS) on neuroinflammation induced with IL-1β in SK-N-SH neuroblastoma cells. We then attempted to elucidate the mechanisms underlying the anti-neuroinflammatory effects of CAS in SK-N-SH cells. Cells were stimulated with 10 U/ml of IL-1β in the presence or absence of different concentrations of CSE (25-200 μg/ml) and CAS (2.5-20 μM). After 24 h incubation, culture media were collected to measure the production of PGE2 and the pro-inflammatory cytokines (TNFα and IL-6). Protein and gene expressions of cyclooxygenase (COX-2) and microsomal prostaglandin synthase-1 (mPGES-1) were studied by immunoblotting and qPCR, respectively. CSE produced significant (p < 0.05) inhibition of TNFα, IL-6 and PGE2 production in SK-N-SH cells. Studies on CAS showed significant and dose-dependent inhibition of TNFα, IL-6 and PGE2 production in IL-1β-stimulated cells without affecting viability. Pre-treatment with CAS (10 and 20 μM) was also found to inhibit IL-1β-induced protein and gene expressions of COX-2 and mPGES-1. Further studies to determine the mechanism of action of CAS showed inhibition of NF-κBp65 nuclear translocation, but not IκB phosphorylation. At 10 and 20 μM, CAS inhibited IL-1β-induced phosphorylation of p38 MAPK. Studies on the downstream substrate of p38, MAPK-activated protein kinase 2 (MAPKAPK2) showed that CAS produced significant (p < 0.05) and dose dependent inhibition of MAPKAPK2 phosphorylation in IL-1β-stimulated SK-N-SH cells. This study clearly shows that cryptolepine (CAS) inhibits neuroinflammation through mechanisms involving inhibition of COX-2 and mPGES-1. It is suggested that these actions are probably mediated through NF

  6. Cytotoxic action of Ganoderma lucidum on interleukin-3 dependent lymphoma DA-1 cells: involvement of apoptosis proteins.

    PubMed

    Calviño, Eva; Pajuelo, Lucía; Casas, Jon A Ochoa de Eribe; Manjón, José Luis; Tejedor, M Cristina; Herráez, Angel; Alonso, Manuel Díez; Diez, José C

    2011-01-01

    Aqueous extracts and a semipurified fraction obtained by methanol extraction and column chromatography were isolated from Ganoderma lucidum [Ganoderma lucidum (Curtis) P. Karst.; Ganodermataceae Donk] and their effects on interleukin 3-dependent lymphoma cells (DA-1) were studied. Cell viability was reduced by the action of unboiled aqueous extract and by the methanol-extracted column-chromatography semipurified fraction, producing DNA fragmentation in DA-1 cells. Treatments with aqueous extracts showed increments of Bax after 13 h, increments of p53 and Mdm2 after 19 h and a reduction of these three proteins after 24 h. The methanol-extracted semipurified fraction also induced increments of p53 and Mdm2 factors at 19 h with a reduction after 24 h. The methanol-extracted column-chromatography semipurified fraction from Ganoderma lucidum produced minor changes in the level of Akt after treatments for 19 h in DA-1 cells with a slight reduction in the levels of NFkB-p65 factor. Both the unboiled aqueous extract and the methanol-extracted column-chromatography semipurified fraction produced cleavage of inactive caspase 3, as a clear indication of induction of apoptosis by compounds present in Ganoderma lucidum. PMID:20568239

  7. The involvement of neuronal nitric oxide synthase in the anti-epileptic action of curcumin on pentylenetetrazol-kindled rats.

    PubMed

    Zhu, Wenting; Su, Jing; Liu, Jing; Jiang, Changbin

    2015-01-01

    In this study, it was investigated whether a NO signaling pathway is involved in the anti-epileptic effect of curcumin on pentylenetetrazol (PTZ)-kindled rats. PTZ-kindled rats received different doses of curcumin that were administered intraperitoneally for 24 days. Either a non-selective inhibitor of nitric oxide synthase (NOS) (N-nitro-L-arginine methyl ester (L-NAME)), a selective inhibitor of neuronal NOS (7-Nitroindazole (7-NI)), a selective inhibitor of inducible NOS (aminoguanidine (AG)), or a NO precursor (L-arginine (L-ARG)) was administered chronically to evaluate the role of NO in curcumin's anti-seizure effect. A chronic administration of curcumin (200 mg/kg) was most effective for decreasing the mean frequency of epileptiform discharge. Furthermore, a pretreatment with L-NAME or 7-NI augmented the anti-epileptic effect of curcumin. In contrast, AG failed to significantly alter the anti-epileptic effect of curcumin. A pretreatment with L-ARG temporally reversed the anti-epileptic effect of curcumin in the early stage, but in the late stage, it potentiated curcumin's anti-epileptic effect. These findings suggest that the L-arginine-nitric oxide pathway may be involved in the anti-epileptic properties of curcumin, and that the role of nNOS (and not iNOS) is prominent in this neuroprotective feature. PMID:26406082

  8. Possible Involvement of µ Opioid Receptor in the Antidepressant-Like Effect of Shuyu Formula in Restraint Stress-Induced Depression-Like Rats

    PubMed Central

    Wang, Fu-rong; Qiao, Ming-qi; Xue, Ling; Wei, Sheng

    2015-01-01

    Recently μ opioid receptor (MOR) has been shown to be closely associated with depression. Here we investigated the action of Shuyu, a Chinese herbal prescription, on repeated restraint stress induced depression-like rats, with specific attention to the role of MOR and the related signal cascade. Our results showed that repeated restraint stress caused significant depressive-like behaviors, as evidenced by reduced body weight gain, prolonged duration of immobility in forced swimming test, and decreased number of square-crossings and rearings in open field test. The stress-induced depression-like behaviors were relieved by Shuyu, which was accompanied by decreased expression of MOR in hippocampus. Furthermore, Shuyu upregulated BDNF protein expression, restored the activity of CREB, and stimulated MEK and ERK phosphorylation in hippocampus of stressed rats. More importantly, MOR is involved in the effects of Shuyu on these depression-related signals, as they can be strengthened by MOR antagonist CTAP. Collectively, these data indicated that the antidepressant-like properties of Shuyu are associated with MOR and the corresponding CREB, BDNF, MEK, and ERK signal pathway. Our study supports clinical use of Shuyu as an effective treatment of depression and also suggests that MOR might be a target for treatment of depression and developing novel antidepressants. PMID:25821488

  9. Informatic support for processing the data regarding the environment factors possibly involved in the etiopathogenesis of insulin-dependent diabetes mellitus ETIODIAB.

    PubMed

    Alecu, S; Dadarlat, V; Stanciu, E; Ionescu-Tirgoviste, C; Konerth, A M

    1997-01-01

    Diabetes represents a heterogeneous group of disturbances, which can have a different aetiology, but have in common glucidic, lipidic and proteinic metabolic disturbances. Insulin-dependent diabetes appears in genetically susceptible persons, as an autoimmune disease activated by environment factors. Epidemiological studies performed in different countries, notice the increasing of diabetes cases in the last decades. Therefore the informatic system EtioDiab (from Etiopathological diabetes) has been developed. The purpose of this system is to assist the medical research regarding the environment factors involved in the etiopathogenesis of insulin-dependent diabetes. The system offers the possibility of calculation of many statistic indicators, of graphic representation of the recorded data, of verification of the statistical hypotheses. PMID:10179563

  10. A protein kinase antigenically related to pp60v-src possibly involved in yeast cell cycle control: positive in vivo regulation by sterol.

    PubMed Central

    Dahl, C; Biemann, H P; Dahl, J

    1987-01-01

    The effects of ergosterol, yeast's natural sterol, on cell cycling and a protein kinase antigenically related to pp60v-src were examined in a sterol auxotroph of Saccharomyces cerevisiae. Sterol-depleted cells accumulate in an unbudded, G1 state. Cell budding and proliferation are reinitiated upon addition of nonlimiting ergosterol or cholesterol with trace ergosterol, whereas cholesterol or trace ergosterol alone is less effective. Stimulation of a protein kinase associated with immune complexes of yeast protein and anti-pp60v-src shows a positive correlation with exit from the G1 phase following ergosterol addition. Ergosterol-stimulated cells also demonstrate an increase in phosphatidylinositol kinase activity. The data suggest that hormonal levels of ergosterol (effective concentration, approximately equal to 1 nM) participate in a signaling process associated with a protein kinase possibly involved in yeast cell cycle control. Images PMID:2438691

  11. Intracellular signal transduction of PBAN action in the silkworm, Bombyx mori: involvement of acyl CoA reductase.

    PubMed

    Ozawa, R; Matsumoto, S

    1996-03-01

    In the silkworm, Bombyx mori, production of the sex pheromone bombykol is regulated by a neurohormone termed PBAN. We have detected the activity of acyl CoA reductase in the pheromone gland of B. mori by using palmitoyl CoA as a substrate. The acyl CoA reductase requires NADPH, but not NADH, as a proton dono. When the pheromone gland was incubated with the PBAN fragment peptide TKYFSPRLamide, palmitoyl CoA was incorporated and converted into the corresponding C16 alcohols. Radio HPLC analysis revealed that these C16 alcohols were hexadecan-1-ol (81.2%), (Z)-11-hexadecen-1-ol (12.3%), and (E, Z)-10, 12-hexadecadien-1-ol (= bombykol, 6.5%). The production of C16 alcohols in the pheromone gland was inhibited by the known bombykol biosynthesis inhibitors EDTA, LaCl3, W-7, trifluoperazine, p-nitrophenyl phosphate, NaF and compactin. By contrast, when the pheromone gland homogenate was incubated in the presence of palmitoyl CoA and NADPH, production of C16 alcohols was affected by compactin, W-7 and trifluoperazine, but not by EDTA, LaCl3, p-nitrophenyl phosphate and NaF. These results indicate that compactin, W-7 and trifluoperazine directly suppress the step catalyzed by acyl CoA reductase, whereas EDTA, LaCl3, pNPP, and NaF inhibit bombykol production by affecting other biochemical steps in the signal transduction of PBAN action. The present results also imply that PBAN regulates the step catalyzed by acyl CoA reductase and that palmitoyl CoA could be used as a substrate of the acyl CoA reductase that regulates bombykol biosynthesis. PMID:8900596

  12. Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a kampo (traditional Japanese) medicine, daikenchuto.

    PubMed

    Tokita, Yohei; Yamamoto, Masahiro; Satoh, Kazuko; Nishiyama, Mitsue; Iizuka, Seiichi; Imamura, Sachiko; Kase, Yoshio

    2011-01-01

    This study focused on the localization of transient receptor potential vanilloid type 1 (TRPV1) in the intestines in postoperative adhesion model rats and investigated the underlying mechanism for the anti-adhesion action of daikenchuto (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA was examined by in situ hybridization and real-time RT-PCR. The effects of DKT and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP-channel antagonist, on talc-induced intestinal adhesions were evaluated. The level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA expression was identified in the submucosal plexus of both sham-operated and talc-treated rats; and in talc-treated rats, it was observed also in the myenteric plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool significantly prevented formation of intestinal adhesions. The effects of DKT and hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These results suggest that pharmacological modulation of TRPV1 might be a possible therapeutic option in postoperative intestinal adhesion, which might be relevant to the prevention of postoperative adhesive obstruction by DKT. PMID:21186335

  13. Studies on the involvement of lysosomes in estrogen action, I. Isolation and enzymatic properties of pig endometrial lysosomes.

    PubMed

    Sierralta, W; Truitt, A J; Jungblut, P W

    1978-04-01

    Pig endometrium cells, collected by curettage and homogenized in an all-glass Potter Elvehjem homogenizer, gave a considerably higher yield of intact mitochondria and lysosomes than homogenates of whole uterus obtained with the Ultraturrax or the Parr bomb. After homogenization of the cells and subfractionation in the presence of Mg2, mitochondria and lysosomes equilibrated at the same modal density in isopycnic centrifugation. Homogenization and subfractionation in buffers devoid of divalent cations and containing EDTA resulted in a decrease in the buoyant density of mitochondria, allowing for a separation from lysosomes. The pH optima and the specific activities of two mitochondrial enzymes and eight hydrolyases used as marker enzymes were determined. The morphological characteristics of fractions were established by electron microscopy. Preliminary results indicate an involvement of lysosomes in steroid metabolism rather than in steroid and receptor translocation into the nucleus. PMID:25838

  14. Genomic organization of the Neurospora crassa gsn gene: possible involvement of the STRE and HSE elements in the modulation of transcription during heat shock.

    PubMed

    Freitas, F Zanolli; Bertolini, M C

    2004-12-01

    Glycogen synthase, an enzyme involved in glycogen biosynthesis, is regulated by phosphorylation and by the allosteric ligand glucose-6-phosphate (G6P). In addition, enzyme levels can be regulated by changes in gene expression. We recently cloned a cDNA for glycogen synthase ( gsn) from Neurospora crassa, and showed that gsn transcription decreased when cells were exposed to heat shock (shifted from 30 degrees C to 45 degrees C). In order to understand the mechanisms that control gsn expression, we isolated the gene, including its 5' and 3' flanking regions, from the genome of N. crassa. An ORF of approximately 2.4 kb was identified, which is interrupted by four small introns (II-V). Intron I (482 bp) is located in the 5'UTR region. Three putative Transcription Initiation Sites (TISs) were mapped, one of which lies downstream of a canonical TATA-box sequence (5'-TGTATAAA-3'). Analysis of the 5'-flanking region revealed the presence of putative transcription factor-binding sites, including Heat Shock Elements (HSEs) and STress Responsive Elements (STREs). The possible involvement of these motifs in the negative regulation of gsn transcription was investigated using Electrophoretic Mobility Shift Assays (EMSA) with nuclear extracts of N. crassa mycelium obtained before and after heat shock, and DNA fragments encompassing HSE and STRE elements from the 5'-flanking region. While elements within the promoter region are involved in transcription under heat shock, elements in the 5'UTR intron may participate in transcription during vegetative growth. The results thus suggest that N. crassa possesses trans -acting elements that interact with the 5'-flanking region to regulate gsn transcription during heat shock and vegetative growth. PMID:15558319

  15. ROS Involves the Fungicidal Actions of Thymol against Spores of Aspergillus flavus via the Induction of Nitric Oxide

    PubMed Central

    Shen, Qingshan; Zhou, Wei; Li, Hongbo; Hu, Liangbin; Mo, Haizhen

    2016-01-01

    Aspergillus flavus is a well-known pathogenic fungus for both crops and human beings. The acquisition of resistance to azoles by A. flavus is leading to more failures occurring in the prevention of infection by A. flavus. In this study, we found that thymol, one of the major chemical constituents of the essential oil of Monarda punctate, had efficient fungicidal activity against A. flavus and led to sporular lysis. Further studies indicated that thymol treatment induced the generation of both ROS and NO in spores, whereas NO accumulation was far later than ROS accumulation in response to thymol. By blocking ROS production with the inhibitors of NADPH oxidase, NO generation was also significantly inhibited in the presence of thymol, which indicated that ROS induced NO generation in A. flavus in response to thymol treatment. Moreover, the removal of either ROS or NO attenuated lysis and death of spores exposed to thymol. The addition of SNP (exogenous NO donor) eliminated the protective effects of the inhibitors of NADPH oxidase on thymol-induced lysis and death of spores. Taken together, it could be concluded that ROS is involved in spore death induced by thymol via the induction of NO. PMID:27196096

  16. ANTI-APOPTOTIC ACTIONS OF VASOPRESSIN IN H32 NEURONS INVOLVE MAP KINASE TRANSACTIVATION AND BAD PHOSPHORYLATION

    PubMed Central

    Chen, Jun; Volpi, Simona; Aguilera, Greti

    2008-01-01

    Vasopressin (VP) secreted within the brain modulates neuronal function acting as a neurotransmitter. Based on the observation that VP prevented serum deprivation-induced cell death in the neuronal cell line, H32, which expresses endogenous V1 receptors, we tested the hypothesis that VP has anti-apoptotic properties. Flow cytometry experiments showed that 10nM VP prevented serum deprivation-induced cell death and annexin V binding. Serum deprivation increased caspase-3 activity in a time and serum concentration dependent manner, and VP prevented these effects through interaction with receptors of V1 subtype. The signaling pathways mediating the anti-apoptotic effect of VP involve mitogen activated protein (MAP) kinase and extracellular signal-regulated kinases (ERK), Ca2+/calmodulin dependent kinase (CaMK) and protein kinase C (PKC). Western blot analyses revealed time-dependent decreases of Bad phosphorylation and increases in cytosolic levels of cytochrome c following serum deprivation, effects which were prevented by 10nM VP. These data demonstrate that activation of endogenous V1 VP receptors prevents serum deprivation-induced apoptosis, through phosphorylation-inactivation of the pro-apoptotic protein, Bad, and consequent decreases in cytosolic cytochome c and caspase-3 activation. The data suggest that VP has anti-apoptotic activity in neurons and that VP may act as a neuroprotective agent in the brain. PMID:18402937

  17. ROS Involves the Fungicidal Actions of Thymol against Spores of Aspergillus flavus via the Induction of Nitric Oxide.

    PubMed

    Shen, Qingshan; Zhou, Wei; Li, Hongbo; Hu, Liangbin; Mo, Haizhen

    2016-01-01

    Aspergillus flavus is a well-known pathogenic fungus for both crops and human beings. The acquisition of resistance to azoles by A. flavus is leading to more failures occurring in the prevention of infection by A. flavus. In this study, we found that thymol, one of the major chemical constituents of the essential oil of Monarda punctate, had efficient fungicidal activity against A. flavus and led to sporular lysis. Further studies indicated that thymol treatment induced the generation of both ROS and NO in spores, whereas NO accumulation was far later than ROS accumulation in response to thymol. By blocking ROS production with the inhibitors of NADPH oxidase, NO generation was also significantly inhibited in the presence of thymol, which indicated that ROS induced NO generation in A. flavus in response to thymol treatment. Moreover, the removal of either ROS or NO attenuated lysis and death of spores exposed to thymol. The addition of SNP (exogenous NO donor) eliminated the protective effects of the inhibitors of NADPH oxidase on thymol-induced lysis and death of spores. Taken together, it could be concluded that ROS is involved in spore death induced by thymol via the induction of NO. PMID:27196096

  18. Stimulation by parathyroid hormone of sup 45 Ca sup 2+ uptake in osteoblast-like cells: Possible involvement of alkaline phosphatase

    SciTech Connect

    Fukayama, S.; Tashjian, A.H. Jr. )

    1990-04-01

    We have investigated the actions of human PTH (hPTH-(1-34)) on the association of 45Ca2+ with two human (SaOS-2 and MG-63) and two rat (ROS 17/2.8 and UMR-106) osteoblast-like cell types. In SaOS-2 cells, hPTH-(1-34) binds to specific membrane receptors to activate adenylate cyclase. Treatment of SaOS-2 cells with hPTH-(1-34) resulted in an increase in 45Ca2+ uptake, in a dose-dependent fashion, up to 2- to 4-fold above control values. The increase was first evident at 10 min and persisted for at least 30 min. Treatment with nimodipine, a calcium channel antagonist, was without effect on the stimulatory action of PTH. A similar enhancement of cell-associated 45Ca2+ was observed when the cells were incubated with vasoactive intestinal peptide, which acts via different receptors to activate adenylate cyclase in SaOS-2 cells. Treatment with (Bu)2cAMP also induced an increase in cell-associated 45Ca2+. Pretreatment of SaOS-2 cells with hPTH-(1-34) for 4 h, which induced homologous desensitization to a second challenge with the same peptide for stimulation of cAMP production, did not attenuate the further enhancement of cell-associated 45Ca2+ by a second treatment with hPTH-(1-34). We then examined a possible relationship between alkaline phosphatase (ALPase) and 45Ca2+ uptake. SaOS-2 cells contained high levels of alkaline phosphatase activity and continuously released the enzyme into the medium. Release was enhanced by treatment with hPTH-(1-34) for 10 min. Incubation of cells with levamisole (an inhibitor of the liver/bone/kidney type of ALPase) resulted in a rapid decrease in basal and PTH-stimulated 45Ca2+ uptake, while treatment with L-Phe-Gly-Gly was without effect. Treatment of the cells with ALPase (bovine kidney) enhanced 45Ca2+ uptake. In MG-63 cells, a stimulatory effect of hPTH-(1-34) on cell-associated 45Ca2+ was also observed; however, hPTH-(1-34) did not stimulate cAMP production in MG-63 cells.

  19. Antinociceptive, anti-inflammatory and smooth muscle relaxant activities of the pyrrolo[3,4-d]pyridazinone derivatives: Possible mechanisms of action.

    PubMed

    Mogilski, Szczepan; Kubacka, Monika; Redzicka, Aleksandra; Kazek, Grzegorz; Dudek, Magdalena; Malinka, Wiesław; Filipek, Barbara

    2015-06-01

    The aim of this study was to evaluate the analgesic as well as anti-inflammatory activities of the new pyrrolo[3,4-d]pyridazinone derivatives. Moreover, the present study attempted to assess some of the mechanisms involved in the pharmacological activity of these compounds. In the previous studies it was shown that these compounds were highly active in the phenylbenzoquinone-induced 'writhing syndrome' test and had much lower activity in the hot plate, which indicates that mainly peripheral mechanisms of analgesia are involved in their effects. In these extended studies the analgesic activity of two tested compounds (4c, 4f) was confirmed in some animal models of pain. The studied compounds showed a significant and dose-related antinociceptive effect in the models of pain induced by formalin, capsaicin and glutamic acid. Both compounds decreased the edema formation and one of them (4c) attenuated mechanical hyperalgesia in carrageenan-induced paw inflammation in rats. Furthermore, both compounds inhibited cell migration, plasma exudation and nociceptive reaction in zymosan A-induced mouse peritonitis. In the subsequent studies, including experiments on isolated organs (ileum, trachea, aorta), radioligand assays and biochemical tests, it was demonstrated that analgesic and anti-inflammatory effects of the investigated structures are largely due to their competitive antagonism for histamine H1 receptor. The influence on the level of cAMP in inflammatory cells (shown in RAW 264.7 macrophages) and subsequent inhibition of cytokine (TNFα, IL-1β) release can also be one of the important mechanisms of their action. Moreover some additional mechanisms may also be involved in the eventual analgesic effect of tested pyrrolo[3,4-d]pyridazinone derivatives. PMID:25847619

  20. Mechanisms Involved in the Anti-Inflammatory Action of a Polysulfated Fraction from Gracilaria cornea in Rats

    PubMed Central

    Coura, Chistiane Oliveira; Souza, Ricardo Basto; Rodrigues, José Ariévilo Gurgel; Vanderlei, Edfranck de Sousa Oliveira; de Araújo, Ianna Wivianne Fernandes; Ribeiro, Natássia Albuquerque; Frota, Annyta Fernandes; Ribeiro, Kátia Alves; Chaves, Hellíada Vasconcelos; Pereira, Karuza Maria Alves; da Cunha, Rodrigo Maranguape Silva; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2015-01-01

    The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI) were investigated using a paw edema model induced in rats by different inflammatory agents (carrageenan, dextran, serotonin, bradykinin, compound 48/80 or L-arginine). Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously - s.c., significantly inhibited rat paw edema induced by carrageenan and dextran, as confirmed by myeloperoxidase and Evans’ blue assessments, respectively. Gc-FI (9 mg/kg, s.c.) inhibited rat paw edema induced by histamine, compound 48/80 and L-arginine. Additionally, Gc-FI (9 mg/kg, s.c.) inhibited Cg-induced edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2 mRNA and protein levels compared with those of the carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with ZnPP IX, a specific heme oxygenase-1 (HO-1) inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena. PMID:25807556

  1. Involvement of 5-HT3 receptors in the action of vortioxetine in rat brain: Focus on glutamatergic and GABAergic neurotransmission.

    PubMed

    Riga, Maurizio S; Sánchez, Connie; Celada, Pau; Artigas, Francesc

    2016-09-01

    The antidepressant vortioxetine is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin (5-HT) transporter (SERT) inhibitor. Vortioxetine occupies all targets at high therapeutic doses and only SERT and 5-HT3-R at low doses. Vortioxetine increases extracellular monoamine concentrations in rat forebrain more than selective serotonin reuptake inhibitors (SSRI) and shows pro-cognitive activity in preclinical models. Given its high affinity for 5-HT3-R (Ki = 3.7 nM), selectively expressed in GABA interneurons, we hypothesized that vortioxetine may disinhibit glutamatergic and monoaminergic neurotransmission following 5-HT3-R blockade. Here we assessed vortioxetine effect on pyramidal neuron activity and extracellular 5-HT concentration using in vivo extracellular recordings of rat medial prefrontal cortex (mPFC) pyramidal neurons and microdialysis in mPFC and ventral hippocampus (vHPC). Vortioxetine, but not escitalopram, increased pyramidal neuron discharge in mPFC. This effect was prevented by SR57227A (5-HT3-R agonist) and was mimicked by ondansetron (5-HT3-R antagonist) and by escitalopram/ondansetron combinations. In microdialysis experiments, ondansetron augmented the 5-HT-enhancing effect of escitalopram in mPFC and vHPC. Local ondansetron in vHPC augmented escitalopram effect, indicating the participation of intrinsic mechanisms. Since 5-HT neurons express GABAB receptors, we examined their putative involvement in controlling 5-HT release after 5-HT3-R blockade. Co-perfusion of baclofen (but not muscimol) reversed the increased 5-HT levels produced by vortioxetine and escitalopram/ondansetron combinations in vHPC. The present results suggest that vortioxetine increases glutamatergic and serotonergic neurotransmission in rat forebrain by blocking 5-HT3 receptors in GABA interneurons. PMID:27106166

  2. HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4

    PubMed Central

    Cai, Jingjing; Yuan, Hong; Wang, Qingde; Yang, Huan; Al-Abed, Yousef; Hua, Zhong; Wang, Jiemei; Chen, Dandan; Wu, Jinze; Lu, Ben; Pribis, John P.; Jiang, Weihong; Yang, Kan; Hackam, David J.; Tracey, Kevin J.; Billiar, Timothy R.; Chen, Alex F.

    2016-01-01

    Objective Endoluminal vascular interventions such as angioplasty initiate a sterile inflammatory response resulting from local tissue damage. This response drives the development of intimal hyperplasia (IH) that, in turn, can lead to arterial occlusion. We hypothesized that the ubiquitous nuclear protein and damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is one of the endogenous mediators that activates processes leading to IH after endoluminal injury to the arterial wall. The aim of this study is to investigate whether approaches that reduce the levels of HMGB1 or inhibit its activity suppresses IH after arterial injury. Approach and Results Here, we show that HMGB1 regulates IH in a mouse carotid wire injury model. Induced genetic deletion or neutralization of HMGB1 prevents IH, monocyte recruitment, and smooth muscle cell growth factor production after endoluminal carotid artery injury. A specific inhibitor of HMGB1 myeloid differentiation factor 2–toll-like receptor 4 (TLR4) interaction, P5779, also significantly inhibits IH. HMGB1 deletion is mimicked in this model by global deletion of TLR4 and partially replicated by myeloid-specific deletion of TLR4 but not TLR2 or receptor for advanced glycation endproducts deletion. The specific HMGB1 isoform known to activate TLR4 signaling (disulfide HMGB1) stimulates smooth muscle cell to migrate and produce monocyte chemotactic protein 1/CCL2) via TLR4. Macrophages produce smooth muscle cell mitogens in response to disulfide HMGB1 also in a TLR4/myeloid differentiation primary response gene (88)/Trif-dependent manner. Conclusions These findings place HMGB1 and its receptor, TLR4 as critical regulators of the events that drive the inflammation leading to IH after endoluminal arterial injury and identify this pathway as a possible therapeutic target to limit IH to attenuate damage-associated molecular pattern molecule–mediated vascular inflammatory responses. PMID:26515416

  3. Involvement of capsaicin-sensitive nerves in the bronchomotor effects of arachidonic acid and melittin: a possible role for lipoxin A4.

    PubMed Central

    Manzini, S.; Meini, S.

    1991-01-01

    1. Functional studies have been performed to evaluate the potential involvement of capsaicin-sensitive nerves in the bronchomotor responses evoked by lipid mediators produced from the metabolic breakdown of arachidonic acid (AA) in the guinea-pig bronchus. 2. In the presence of indomethacin, the exogenous administration of AA (0.01-1 mM) produced a concentration-dependent contractile response in guinea-pig isolated bronchial rings. AA-induced contractions were augmented by epithelium-removal and by thiorphan (10 microM), an inhibitor of tachykinin breakdown. A sustained downward and rightward displacement of the complete concentration-response curve to AA was observed after in vitro capsaicin desensitization. 3. BWA4C (1 microM), a selective inhibitor of 5-lipoxygenase, shifted the AA concentration-response curve to the right. In the presence of this inhibitor, capsaicin desensitization did not have any further inhibitory action. 4. A potent, concentration-dependent and capsaicin-sensitive bronchoconstrictor effect was also observed with the polypeptide, melittin (10 nM-1 microM), an activator of phospholipase A2, which therefore should generate endogenous AA. 5. In vitro capsaicin-desensitization produced a significant reduction of the bronchomotor responses evoked by lipoxin A4 (1-6 microM), but not of those elicited by other lipoxygenases products such as leukotriene D4 (1-100 nM) or by 15-hydroxyeicosatetraenoic acid (15-HETE, 1-6 microM). 6. These findings indicate that lipoxin A4 but not leukotriene D4 or 15-HETE, might be one of the lipoxygenase mediators of excitatory effects of AA on capsaicin-sensitive sensory nerves. PMID:1908731

  4. Cell cycle alterations induced by urban PM2.5 in bronchial epithelial cells: characterization of the process and possible mechanisms involved

    PubMed Central

    2013-01-01

    Background This study explores and characterizes cell cycle alterations induced by urban PM2.5 in the human epithelial cell line BEAS-2B, and elucidates possible mechanisms involved. Methods The cells were exposed to a low dose (7.5 μg/cm2) of Milan winter PM2.5 for different time points, and the cell cycle progression was analyzed by fluorescent microscopy and flow cytometry. Activation of proteins involved in cell cycle control was investigated by Western blotting and DNA damage by 32P-postlabelling, immunostaining and comet assay. The formation of reactive oxygen species (ROS) was quantified by flow cytometry. The role of PM organic fraction versus washed PM on the cell cycle alterations was also examined. Finally, the molecular pathways activated were further examined using specific inhibitors. Results Winter PM2.5 induced marked cell cycle alteration already after 3 h of exposure, represented by an increased number of cells (transient arrest) in G2. This effect was associated with an increased phosphorylation of Chk2, while no changes in p53 phosphorylation were observed at this time point. The increase in G2 was followed by a transient arrest in the metaphase/anaphase transition point (10 h), which was associated with the presence of severe mitotic spindle aberrations. The metaphase/anaphase delay was apparently followed by mitotic slippage at 24 h, resulting in an increased number of tetraploid G1 cells and cells with micronuclei (MN), and by apoptosis at 40 h. Winter PM2.5 increased the level of ROS at 2 h and DNA damage (8-oxodG, single- and double stand breaks) was detected after 3 h of exposure. The PM organic fraction caused a similar G2/M arrest and augmented ROS formation, while washed PM had no such effects. DNA adducts were detected after 24 h. Both PM-induced DNA damage and G2 arrest were inhibited by the addition of antioxidants and α-naphthoflavone, suggesting the involvement of ROS and reactive electrophilic metabolites formed via a P

  5. Human factors involved in perception and action in a natural stereoscopic world: an up-to-date review with guidelines for stereoscopic displays and stereoscopic virtual reality (VR)

    NASA Astrophysics Data System (ADS)

    Perez-Bayas, Luis

    2001-06-01

    In stereoscopic perception of a three-dimensional world, binocular disparity might be thought of as the most important cue to 3D depth perception. Nevertheless, in reality there are many other factors involved before the 'final' conscious and subconscious stereoscopic perception, such as luminance, contrast, orientation, color, motion, and figure-ground extraction (pop-out phenomenon). In addition, more complex perceptual factors exist, such as attention and its duration (an equivalent of 'brain zooming') in relation to physiological central vision, In opposition to attention to peripheral vision and the brain 'top-down' information in relation to psychological factors like memory of previous experiences and present emotions. The brain's internal mapping of a pure perceptual world might be different from the internal mapping of a visual-motor space, which represents an 'action-directed perceptual world.' In addition, psychological factors (emotions and fine adjustments) are much more involved in a stereoscopic world than in a flat 2D-world, as well as in a world using peripheral vision (like VR, using a curved perspective representation, and displays, as natural vision does) as opposed to presenting only central vision (bi-macular stereoscopic vision) as in the majority of typical stereoscopic displays. Here is presented the most recent and precise information available about the psycho-neuro- physiological factors involved in the perception of stereoscopic three-dimensional world, with an attempt to give practical, functional, and pertinent guidelines for building more 'natural' stereoscopic displays.

  6. Evidence that glucose metabolism is decreased in the cerebrum of aged female senescence-accelerated mouse; possible involvement of a low hexokinase activity.

    PubMed

    Kurokawa, T; Sato, E; Inoue, A; Ishibashi, S

    1996-08-16

    d-Glucose metabolism in cerebral cells prepared from aged senescence-accelerated mouse (SAM), was investigated in consideration of a sex difference. The production of 14CO2 from 6-[14C]D-glucose was reduced in female senescence-accelerated-prone mouse (SAMP) 8, a prone substrain, in comparison with that in female senescence-accelerated-resistant mouse (SAMR) 2, a control substrain, whereas there was no difference in males. The 2-deoxy-D-glucose uptake into cerebral cells from female SAMP8 was also lower than that of control mice. But, the 3-O-methyl-D-glucose uptake in SAMP8 was higher than that of SAMR2, suggesting that the low hexokinase activity was involved in the decreased glucose metabolism in cerebrum of SAMP8 females irrespective of glucose transporter. This possibility was supported by the finding that the contents of glucose 6-phosphate produced from glucose added to cerebral cells from SAMP8 was lower than that in ICR mice. PMID:8873128

  7. Diclofenac-Induced Apoptosis in the Neuroblastoma Cell Line SH-SY5Y: Possible Involvement of the Mitochondrial Superoxide Dismutase

    PubMed Central

    Cecere, Francesca; Iuliano, Annarita; Albano, Francesco; Zappelli, Claudia; Castellano, Immacolata; Grimaldi, Pasquale; Masullo, Mariorosario; De Vendittis, Emmanuele; Ruocco, Maria Rosaria

    2010-01-01

    Diclofenac, a nonsteroidal anti-inflammatory drug, induces apoptosis on the neuroblastoma cell line SH-SY5Y through a mitochondrial dysfunction, affecting some antioxidant mechanisms. Indeed, the time- and dose-dependent increase of apoptosis is associated to an early enhancement of the reactive oxygen species (ROS). Mitochondrial superoxide dismutase (SOD2) plays a crucial role in the defence against ROS, thus protecting against several apoptotic stimuli. Diclofenac decreased the protein levels and the enzymatic activity of SOD2, without any significant impairment of the corresponding mRNA levels in the SH-SY5Y extracts. When cells were incubated with an archaeal exogenous thioredoxin, an attenuation of the diclofenac-induced apoptosis was observed, together with an increase of SOD2 protein levels. Furthermore, diclofenac impaired the mitochondrial membrane potential, leading to a release of cytochrome c. These data suggest that mitochondria are involved in the diclofenac-induced apoptosis of SH-SY5Y cells and point to a possible role of SOD2 in this process. PMID:20625417

  8. Anatomy of the antennal dorsal organ in female of Neodryinus typhlocybae (Hymenoptera: Dryinidae): A peculiar sensory structure possibly involved in perception of host vibration.

    PubMed

    Riolo, Paola; Isidoro, Nunzio; Ruschioni, Sara; Minuz, Roxana L; Bin, Ferdinando; Romani, Roberto

    2016-01-01

    Neodryinus typhlocybae (Hymenoptera: Dryinidae) is a natural enemy of the planthopper Metcalfa pruinosa, which was introduced from North America into Europe and has become established in various regions as a pest species. Vibrational signals play a crucial role in the communication of M. pruinosa, which appears to be exploited by N. typhlocybae. Scanning and transmission electron microscopy have shown that the antennae of N. typhlocybae females have peculiar and complex sensory structures: deep longitudinal grooves that house long sensilla trichodea, termed here "Antennal Dorsal Organs." Such structures were not present on male antennae. These sensilla extend for the length of the grooves, without contact with the groove cuticle. Their hair shaft is empty and aporous, and inserted into a specialized socket, underneath which there is a cuticular ampulla-like chamber. Each sensillum is associated with two sensory neurons: one terminates at the proximal end of the dendritic sheath; the other continues into the sensillum sinus and is enclosed in the dendritic sheath. This second sensory neuron then enters the ampulla-like chamber through the circular opening, and then terminates with a conspicuous tubular body at the shaft base. The possible involvement of this peculiar structure in the context of host recognition mechanism is discussed. PMID:26460191

  9. Transcriptional profiling analysis of Spodoptera litura larvae challenged with Vip3Aa toxin and possible involvement of trypsin in the toxin activation

    PubMed Central

    Song, Feifei; Chen, Chen; Wu, Songqing; Shao, Ensi; Li, Mengnan; Guan, Xiong; Huang, Zhipeng

    2016-01-01

    Vip proteins, a new group of insecticidal toxins produced by Bacillus thuringiensis, are effective against specific pests including Spodoptera litura. Here, we report construction of a transcriptome database of S. litura by de novo assembly along with detection of the transcriptional response of S. litura larvae to Vip3Aa toxin. In total, 56,498 unigenes with an N50 value of 1,853 bp were obtained. Results of transcriptome abundance showed that Vip3Aa toxin provoked a wide transcriptional response of the S. litura midgut. The differentially expressed genes were enriched for immunity-related, metabolic-related and Bt-related genes. Twenty-nine immunity-related genes, 102 metabolic-related genes and 62 Bt-related genes with differential expression were found. On the basis of transcriptional profiling analysis, we focus on the functional validation of trypsin which potentially participated in the activation of Vip3Aa protoxin. Zymogram analysis indicated that the presence of many proteases, including trypsin, in S. litura larvae midgut. Results of enzymolysis in vitro of Vip3Aa by trypsin, and bioassay and histopathology of the trypsin-digested Vip3Aa toxin showed that trypsin was possibly involved in the Vip3Aa activation. This study provides a transcriptome foundation for the identification and functional validation of the differentially expressed genes in an agricultural important pest, S. litura. PMID:27025647

  10. Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.

    PubMed

    Chanana, Priyanka; Kumar, Anil

    2016-04-01

    Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. PMID:26848139

  11. Transcriptional profiling analysis of Spodoptera litura larvae challenged with Vip3Aa toxin and possible involvement of trypsin in the toxin activation.

    PubMed

    Song, Feifei; Chen, Chen; Wu, Songqing; Shao, Ensi; Li, Mengnan; Guan, Xiong; Huang, Zhipeng

    2016-01-01

    Vip proteins, a new group of insecticidal toxins produced by Bacillus thuringiensis, are effective against specific pests including Spodoptera litura. Here, we report construction of a transcriptome database of S. litura by de novo assembly along with detection of the transcriptional response of S. litura larvae to Vip3Aa toxin. In total, 56,498 unigenes with an N50 value of 1,853 bp were obtained. Results of transcriptome abundance showed that Vip3Aa toxin provoked a wide transcriptional response of the S. litura midgut. The differentially expressed genes were enriched for immunity-related, metabolic-related and Bt-related genes. Twenty-nine immunity-related genes, 102 metabolic-related genes and 62 Bt-related genes with differential expression were found. On the basis of transcriptional profiling analysis, we focus on the functional validation of trypsin which potentially participated in the activation of Vip3Aa protoxin. Zymogram analysis indicated that the presence of many proteases, including trypsin, in S. litura larvae midgut. Results of enzymolysis in vitro of Vip3Aa by trypsin, and bioassay and histopathology of the trypsin-digested Vip3Aa toxin showed that trypsin was possibly involved in the Vip3Aa activation. This study provides a transcriptome foundation for the identification and functional validation of the differentially expressed genes in an agricultural important pest, S. litura. PMID:27025647

  12. Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines.

    PubMed

    Flocke, Lea S; Trondl, Robert; Jakupec, Michael A; Keppler, Bernhard K

    2016-06-01

    Sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) is a clinically investigated ruthenium-based metal complex, which shows promising results in solid tumors, such as non-small cell lung cancer, colorectal carcinoma, and most distinctively in gastrointestinal neuroendocrine tumors. In previous studies, fast binding to albumin as well as transferrin could be shown. The enhanced permeability and retention (EPR) effect, which is diversely being exploited for tumor targeting, could therefore be applicable for NKP-1339. Here we studied the serum dependence of its biological activity in various methods, influencing its cellular accumulation, cytotoxicity as well as the generation of reactive oxygen species (ROS). ROS lead to Nrf2 activation, which is known to activate antioxidant response gene transcription. GRP78 down-regulation on the protein level suggests ER associated protein degradation (ERAD) as a mode of action, as RNA levels are only mildly affected. Another important part for the mode of action is endoplasmic reticulum (ER) stress, as different factors are highly upregulated on the protein level. For example PERK, a transmembrane receptor which is released by GRP78 when the ER is disturbed, is upregulated and phosphorylated. EIF2α is phosphorylated, which leads to an inhibition of CAP-dependent translation and other stress responses. The transcription factor CHOP (DDIT3), which promotes ER stress dependent apoptosis, is time and concentration dependently upregulated. Finally cytotoxicity tests could prove that inhibition of ER stress and ER stress-mediated apoptosis leads to decreased cytotoxic effects of NKP-1339, which highlights the involvement of this mechanism in the mode of action. PMID:26988975

  13. Possible mechanisms of action of the compounds injected intralesionally in the treatment of cutaneous leishmaniasis, in addition to their direct effects on the parasites.

    PubMed

    Najim, R A; Sharquie, K E; Al-Zubaidy, S A A

    2006-01-01

    By injecting uninfected rabbits intradermally with one of the test compounds or the isotonic saline (0.9% NaCl) used as a control, the possible mechanisms of the indirect action of some drugs used intralesionally in the treatment of human cutaneous leishmaniasis [sodium stibogluconate, 2% zinc sulphate, and hypertonic (7% NaCL) saline] were explored. The 24 injected rabbits (six for the control and six for each test compound) were followed up for 30 days, both macroscopically, with checks for erythema and increases in skin thickness, and microscopically, with the histopathological examination of sections of biopsies from the injection sites. Although the microscopy revealed inflammatory-cell infiltration, beginning with eosinophils, followed by lymphocytes and finally by the proliferation of fibroblasts, at all of the injection sites, these changes were most intense with the sodium stibogluconate and 2% zinc sulphate, less marked with the hypertonic saline, and minimal and relatively short-lived with the isotonic saline. Presumably as a result of their metal content, sodium stibogluconate and zinc sulphate each probably induce tissue damage and, subsequently, severe inflammatory changes. The antileishmanial activity of hypertonic saline, however, may be entirely attributable to its osmotic effects. PMID:16417711

  14. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress.

    PubMed

    Sun, Jing; Wang, Fangyan; Hong, Guangliang; Pang, Mengqi; Xu, Hailing; Li, Haixiao; Tian, Feng; Fang, Renchi; Yao, Ye; Liu, Jiaming

    2016-04-01

    Sodium butyrate (NaB) has exhibited neuroprotective activity. This study aimed to explore that NaB exerts beneficial effects on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and its possible mechanisms. The behavioral tests including sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) and forced swimming test (FST) were to evaluate the antidepressant effects of NaB. Then changes of Nissl's body in the hippocampus, brain serotonin (5-HT) concentration, brain-derived neurotrophic factor (BDNF) and tight junctions (TJs) proteins level were assessed to explore the antidepressant mechanisms. Our results showed that CUMS caused significant depression-like behaviors, neuropathological changes, and decreased brain 5-HT concentration, TJs protein levels and BDNF expression in the hippocampus. However, NaB treatment significantly ameliorated behavioral deficits of the CUMS-induced mice, increased 5-HT concentration, increased BDNF expression, and up-regulated Occludin and zonula occludens-1(ZO-1) protein levels in the hippocampus, which demonstrated that NaB could partially restore CUMS-induced blood-brain barrier (BBB) impairments. Besides, the pathologic changes were alleviated. In conclusion, these results demonstrated that NaB significantly improved depression-like behaviors in CUMS-induced mice and its antidepressant actions might be related with, at least in part, the increasing brain 5-HT concentration and BDNF expression and restoring BBB impairments. PMID:26957230

  15. The human erythrocyte Cl-dependent Na-K cotransport system as a possible model for studying the action of loop diuretics.

    PubMed Central

    Ellory, J. C.; Stewart, G. W.

    1982-01-01

    1 The recent demonstration of the chloride-dependence of the red cell Na-K cotransport system suggests an analogy between this process and the active Cl- absorption in the ascending loop of Henle, which is the target transport system for loop diuretics. 2 Using red cell K influx, four known loop diuretics, six experimental frusemide analogues, two thiazides, two K-retaining diuretics and one organomercurial were compared for inhibitory potency on the red cell Na-K cotransport system. 3 Except for mersalyl, whose exact mode of action in the kidney is still in doubt, the inhibition of the red cell system by various loop diuretics was consistent with both published whole body diuretic data and isolated perfused tubule studies, while the system did not respond to the thiazides or the K-retaining diuretics. 4 It is concluded that the human red cell Na-K cotransport system is a possible valid model process on which to study the activity of loop diuretics. PMID:7074281

  16. Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

    SciTech Connect

    Goodman, A.B.

    1995-08-14

    Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies. 201 refs., 1 tab.

  17. Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer.

    PubMed

    Shigeta, S; Toyoshima, M; Kitatani, K; Ishibashi, M; Usui, T; Yaegashi, N

    2016-07-01

    Fallopian tubal epithelium is a candidate for the origin of high-grade serous ovarian cancer. Transferrin-containing follicular fluid and/or retrograde menstrual blood are possible risk factors for carcinogenesis. Accumulation of DNA double-strand breaks (DNA-DSBs) in the fallopian tubal epithelium is considered to play an important role in the development of cancer. However, the mechanisms by which DNA-DSBs accumulate have not yet been fully elucidated. The hydroxyl radical, which is produced in a Fenton reaction catalyzed by an iron ion, serves as a potent DNA-DSB-inducing molecule, raising the potential of an iron ion transporter of transferrin in the formation of DNA-DSBs. We studied the potential involvement of transferrin in DNA damage and the development of ovarian cancer. Treatment with transferrin facilitated the formation of histone 2AX phosphorylated at Serine 139 (γH2AX), which is known as a DNA-DSB marker, in human fallopian tube secretory epithelial cells and A2780 ovarian cancer cells. Knockdown of transferrin receptor 1 (TfR1), but not transferrin receptor 2, suppressed the transferrin uptake and consequent formation of γH2AX. As hydroxyl radicals in reactive oxygen species (ROS) are involved in DNA-DSBs, the formation of ROS was determined. Treatment with TfR1-specific small interference RNAs significantly diminished transferrin-induced formation of ROS. Moreover, TfR1-dependent uptake of transferrin was revealed to augment the formation of DNA-DSBs in the presence of hydrogen peroxide, which served as a substrate for the Fenton reaction. An ex vivo study with murine fallopian tubes further demonstrated that transferrin treatment introduced DNA-DSBs in the fallopian tubal epithelium. Collectively, these data suggested that the transferrin-TfR1 axis accounts for the induction of DNA-DSBs that potentially lead to DNA damage/genome instability. These findings also suggested that exposure to transferrin initiates and promotes the development of

  18. Possible involvement of the CA1 GABAA receptors upon acquisition and expression of the ACPA-induced place preference in mice.

    PubMed

    Nasehi, Mohammad; Kamali-Dolatabadi, Leila; Torabi-Nami, Mohammad; Zarrindast, Mohammad-Reza

    2016-07-01

    A plethora of investigations has substantiated a close relationship between cannabinoidergic and GABAergic systems in hippocampal CA1. The crucial role of these two systems in regulation of the addictive behaviors is well described. The aim of the current study was to investigate whether the CA1 GABAA receptors are involved in ACPA (a selective CB1 cannabinoid receptor agonist)-induced rewarding effects using the condition place preference (CPP) protocol. Moreover, the hole-board paradigm was used to measure the exploratory behaviors which may potentially influence this phenomenon. Results showed that ACPA (0.02mg/kg, i.p.) induced CPP. Applying a 3-day conditioning schedule, we found that the sole administration of the GABAA receptor agonist, muscimol (0.125, 0.25 and 0.5μg/mouse; intra-CA1), or the GABAA receptor antagonist, bicuculline (0.0635, 0.125 and 0.25μg/mouse; intra-CA1), fail to induce CPP or CPA (condition place aversion). Similarly, injection of the subthreshold dose of muscimol (0.125μg/mouse, intra-CA1) decreased the CPP acquisition induced by ACPA. Similar intervention with the subthreshold dose of bicuculline (0.125μg/mouse, intra-CA1) did not alter the CPP acquisition induced by ACPA. Furthermore, the sole intra-CA1 administration of muscimol (0.125, 0.25 and 0.5μg/mouse) and bicuculline (0.0635, 0.125 and 0.25μg/mouse; intra-CA1) prior to testing, did not induce CPP or CPA. Similar interventions revealed that muscimol and bicuculline increase and decrease CPP expression induced by ACPA, respectively. The ACPA- and muscimol-induced CPP could be blocked by bicuculline. Taken together, the CA1 GABAA receptors seem to be possibly involved in the modulation of acquisition or expression process upon ACPA-induced CPP. PMID:27090228

  19. Community-Involved Learning to Expand Possibilities for Vulnerable Children: A Critical Communicative, Sen's Capability, and Action Research Approach

    ERIC Educational Resources Information Center

    Kim, Kyung Hi

    2014-01-01

    This research, based on a case study of vulnerable children in Korea, used a mixed methods transformative approach to explore strategies to support and help disadvantaged children. The methodological approach includes three phases: a mixed methods contextual analysis, a qualitative dominant analysis based on Sen's capability approach and…

  20. Mechanism of action of the breast cancer-promoter hormone, 5α-dihydroprogesterone (5αP), involves plasma membrane-associated receptors and MAPK activation.

    PubMed

    Wiebe, John P; Pawlak, Kevin J; Kwok, Arthur

    2016-01-01

    Previous studies have shown that breast tissues and breast cell lines can convert progesterone to 5α-pregnane-3,20-dione (5aP), and that 5αP stimulates breast cell proliferation and detachment in vitro, and tumor formation in vivo, regardless of presence or absence of receptors for progesterone (PR) or estrogen (ER). Recently it was demonstrated, both in vitro and in vivo, that pro-cancer actions attributed to administered progesterone are due to the in situ produced 5αP. Because of the significant role of 5αP in breast cancers, it is important to understand its molecular mechanisms of action. The aims of the current studies were to identify 5αP binding sites and to determine if the mechanisms of action of 5αP involve the mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinases (ERK1/2) pathway. Binding studies, using tritium-labeled 5αP ([(3)H]5αP), carried out on membrane, cytosol and nuclear fractions from human breast cells (MCF-7, PR/ER-positive; MDA-MB-231, PR/ER-negative) and on highly enriched membrane fractions, identified the plasma membrane as the site of ligand specific 5αP receptors. Localization of 5αP receptors to the cell membrane was confirmed visually with fluorescently labeled conjugate (5αP-BSA-FITC). Treatment of cells with either 5αP or membrane-impermeable 5αP-BSA resulted in significant increases in cell proliferation and detachment. 5αP and 5αP-BSA equally activated the MAPK/ERK1/2 pathway as evidenced by phosphorylation of ERK1/2. Inhibitors (PD98059, mevastatin and genistein) of specific sites along the Ras/Raf/MEK/ERK signaling pathway, blocked the phosphorylation and concomitantly inhibited 5αP-induced stimulation of cell proliferation and detachment. The study has identified high affinity, stereo-specific binding sites for 5αP that have the characteristics of a functional membrane 5αP receptor, and has shown that the cancer-promoter actions of 5αP are mediated from the liganded receptor

  1. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  2. Screening of UV-B-induced genes from apple peels by SSH: possible involvement of MdCOP1-mediated signaling cascade genes in anthocyanin accumulation.

    PubMed

    Peng, Ting; Saito, Takanori; Honda, Chikako; Ban, Yusuke; Kondo, Satoru; Liu, Ji-Hong; Hatsuyama, Yoshimichi; Moriguchi, Takaya

    2013-07-01

    Suppression subtractive hybridization (SSH) was employed to identify candidate genes involved in red coloration in apple peel with the ultraviolet (UV)-B-treated 'Mutsu'. After reverse Northern blotting verification, nearly 80 clones were successfully sequenced. Large portions of the expressed sequence tags (ESTs) are well characterized anthocyanin biosynthesis-related genes, such as chalcone synthase (11A5), flavonol synthase (12F3), anthocyanidin synthase (11H5) and UDP-glycosyl transferase (14A12) whose presence proved the success of SSH. Eight ESTs were selected for quantitative real-time polymerase chain reaction analysis and their expressions were all elevated in 'Induction', further confirming the reliability of the SSH library. One EST, 11F4 (CONSTITUTIVE PHOTOMORPHOGENIC 1: COP1) with putative function in light signal relay was further analyzed in 'Mutsu' and 'Tsugaru', along with MdHY5 (ELONGATED HYPOCOTYL 5: the downstream target of COP1), MdMYB22 (a possible flavonol-specific activator under the regulation of HY5, belonging to the SG7/PRODUCTION OF FLAVONOL GLYCOSIDES family) and MdMYBA. Results showed that MdCOP1, MdHY5, MdMYB22 and MdMYBA were all UV-B inducible genes and anthocyanin accumulation occurred after their increased expressions. Moreover, their expressions and anthocyanin content were enhanced under UV-B plus 17°C treatment. The presence of G box, a known consensus binding site of HY5, in the MdMYBA promoter region implicated that it could be regulated by MdHY5, which was verified by the result of the yeast one-hybrid analysis. Our data suggested that UV-B irradiation would induce the utmost upstream light signaling factor, MdCOP1, which activates MdHY5 signaling by binding to the promoter regions of MdMYBs, and finally leads to the red coloration of apple peels. PMID:23171407

  3. Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat.

    PubMed

    Shimizu, Takahiro; Tanaka, Kenjiro; Nakamura, Kumiko; Taniuchi, Keisuke; Yawata, Toshio; Higashi, Youichirou; Ueba, Tetsuya; Dimitriadis, Fotios; Shimizu, Shogo; Yokotani, Kunihiko; Saito, Motoaki

    2014-07-01

    We recently reported that intracerebroventricularly administered 2-arachidonoylglycerol elevated plasma noradrenaline and adrenaline by brain monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms in the rat. These results suggest that 2-arachidonoylglycerol is hydrolyzed by MGL to free arachidonic acid, which is further metabolized to prostaglandins (PGs) by cyclooxygenase in the brain, thereby elevating plasma noradrenaline and adrenaline. On the other hand, 2-arachidonoylglycerol can be also metabolized by cyclooxygenase to PG glycerol esters (PG-Gs), which seems to be hydrolyzed by MGL to free PGs. Here, we examined the involvement of brain PG-Gs in the elevation of plasma noradrenaline and adrenaline regarding PGE2-G and prostanoid EP receptors using anesthetized male Wistar rats. Intracerebroventricularly administered PGE2-G (1.5 and 3 nmol/animal) dose-dependently elevated plasma noradrenaline but not adrenaline. PGE2-G also elevated systolic, mean and diastolic blood pressure and heart rate. The PGE2-G-induced elevation of plasma noradrenaline was attenuated by JZL184 (MGL inhibitor). Intracerebroventricularly administered PGE2 (0.3 and 1.5 nmol/animal) and sulprostone (0.1 and 0.3 nmol/animal) (EP1/EP3 agonist) also elevated plasma noradrenaline but not adrenaline in a dose-dependent manner. The sulprostone-induced elevation was attenuated by L-798,106 (EP3 antagonist), but not by SC-51322 (EP1 antagonist). L-798,106 also attenuated the PGE2-G- and PGE2-induced elevation of plasma noradrenaline, while PF-04418948 (EP2 antagonist) and L-161,982 (EP4 antagonist) had no effect on the PGE2-G-induced response. These results suggest a possibility that brain PGE2-G produced from 2-arachidonoylglycerol can be hydrolyzed to free PGE2, thereby activating central sympathetic outflow by brain prostanoid EP3 receptor-mediated mechanisms in the rat. PMID:24657150

  4. Involving migrants in the development of guidelines for communication in cross-cultural general practice consultations: a participatory learning and action research project

    PubMed Central

    O'Reilly-de Brún, Mary; MacFarlane, Anne; de Brún, Tomas; Okonkwo, Ekaterina; Bonsenge Bokanga, Jean Samuel; Manuela De Almeida Silva, Maria; Ogbebor, Florence; Mierzejewska, Aga; Nnadi, Lovina; van den Muijsenbergh, Maria; van Weel-Baumgarten, Evelyn; van Weel, Chris

    2015-01-01

    Objective The aim of this research was to involve migrants and other key stakeholders in a participatory dialogue to develop a guideline for enhancing communication in cross-cultural general practice consultations. In this paper, we focus on findings about the use of formal versus informal interpreters because dialogues about these issues emerged as central to the identification of recommendations for best practice. Design This qualitative case study involved a Participatory Learning and Action (PLA) research methodology. Participants The sample comprised 80 stakeholders: 51 from migrant communities; 15 general practitioners (GPs) and general practice staff; 7 established migrants as peer researchers; 5 formal, trained interpreters; and 2 service planners from the national health authority. Setting Galway, Ireland. Results There was 100% consensus across stakeholder groups that while informal interpreters have uses for migrants and general practice staff, they are not considered acceptable as best practice. There was also 100% consensus that formal interpreters who are trained and working as per a professional code of practice are acceptable as best practice. Conclusions Policymakers and service planners need to work in partnership with service providers and migrants to progress the implementation of professional, trained interpreters as a routine way of working in general practice. PMID:26391628

  5. Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects on Leishmania amazonensis and Possible Mechanisms of Action

    PubMed Central

    Amorim, Layane Valéria; de Oliveira, Jamylla Mirck Guerra; Dias, Clarice Noleto; Moraes, Denise Fernandes Coutinho; Andrade, Eloisa Helena de Aguiar; Maia, Jose Guilherme Soares; Carneiro, Sabrina Maria Portela; Carvalho, Fernando Aécio de Amorim

    2013-01-01

    Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components were sesquiterpenes (91.92%), with curzerene (47.3%), γ-elemene (14.25%), and trans-β-elemenone (10.4%) being the major constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04 μg·mL−1) and amastigotes (IC50, 1.92 μg·mL−1) suggested significant anti-Leishmania activity. In the cytotoxicity determination, EuEO was 20 times more toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the highest concentration tested (400 μg·mL−1); however, there appeared to be no toxicity at 50 μg·mL−1. While the data show that EuEO activity is not mediated by nitric oxide production, they do suggest that macrophage activation may be involved in EuEO anti-Leishmania activity, as evidenced by increases in both the phagocytic capacity and the lysosomal activity. More studies are needed to determine in vivo activity as well as additional mechanisms of the anti-Leishmania activity. PMID:23533469

  6. Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects on Leishmania amazonensis and Possible Mechanisms of Action.

    PubMed

    Rodrigues, Klinger Antonio da Franca; Amorim, Layane Valéria; de Oliveira, Jamylla Mirck Guerra; Dias, Clarice Noleto; Moraes, Denise Fernandes Coutinho; Andrade, Eloisa Helena de Aguiar; Maia, Jose Guilherme Soares; Carneiro, Sabrina Maria Portela; Carvalho, Fernando Aécio de Amorim

    2013-01-01

    Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components were sesquiterpenes (91.92%), with curzerene (47.3%), γ -elemene (14.25%), and trans- β -elemenone (10.4%) being the major constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04  μ g·mL(-1)) and amastigotes (IC50, 1.92  μ g·mL(-1)) suggested significant anti-Leishmania activity. In the cytotoxicity determination, EuEO was 20 times more toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the highest concentration tested (400  μ g·mL(-1)); however, there appeared to be no toxicity at 50  μ g·mL(-1). While the data show that EuEO activity is not mediated by nitric oxide production, they do suggest that macrophage activation may be involved in EuEO anti-Leishmania activity, as evidenced by increases in both the phagocytic capacity and the lysosomal activity. More studies are needed to determine in vivo activity as well as additional mechanisms of the anti-Leishmania activity. PMID:23533469

  7. A possible mechanism of action of plant growth-promoting rhizobacteria (PGPR) strain Bacillus pumilus WP8 via regulation of soil bacterial community structure.

    PubMed

    Kang, Yijun; Shen, Min; Wang, Huanli; Zhao, Qingxin

    2013-01-01

    According to the traditional view, establishment and maintenance of critical population densities in the rhizosphere was the premise of PGPR to exert growth-promoting effects. In light of the facts that soil bacterial community structures can be changed by some PGPR strains including Bacillus pumilus WP8, we hypothesize that regulation of soil bacterial community structure is one of the plant growth-promoting mechanisms of B. pumilus WP8, rather than depending on high-density cells in soil. In this study, denaturing gradient gel electrophoresis (PCR-DGGE) was performed to evaluate the relationship between changes in soil bacterial community structure and growth-promoting effect on the seedling growth of fava beans (Vicia faba L.) during three successive cultivations. We found that B. pumilus WP8 lacks capacity to reproduce in large enough numbers to survive in bulk soil more than 40 days, yet the bacterial community structures were gradually influenced by inoculation of WP8, especially on dominant populations. Despite WP8 being short-lived, it confers the ability of steadily promoting fava bean seedling growth on soil during the whole growing period for at least 90 days. Pseudomonas chlororaphis RA6, another tested PGPR strain, exists in large numbers for at least 60 days but less than 90 days, whilst giving rise to slight influence on bacterial community structure. In addition, along with the extinction of RA6 cells in bulk soils, the effect of growth promotion disappeared simultaneously. Furthermore, the increment of soil catalase activity from WP8 treatment implied the ability to stimulate soil microbial activity, which may be the reason why the dominant population changed and increased as time passed. Our study suggests that regulation of treated soil bacterial community structure may be another possible action mechanism. PMID:24005176

  8. Possible Mechanism of Action of the Antiallergic Effect of an Aqueous Extract of Heliotropium indicum L. in Ovalbumin-Induced Allergic Conjunctivitis

    PubMed Central

    Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Abokyi, Samuel; Wiredu, Eric Addo

    2015-01-01

    Heliotropium indicum is used traditionally as a remedy for conjunctivitis in Ghana. This study therefore evaluated the antiallergic potential of an aqueous whole plant extract of Heliotropium indicum (HIE) in ovalbumin-induced allergic conjunctivitis and attempted to predict its mode of action. Clinical scores for allergic conjunctivitis induced by intraperitoneal ovalbumin sensitization (100 : 10 μg OVA/Al(OH)3 in phosphate-buffered saline [PBS]) and topical conjunctival challenge (1.5 mg OVA in 10 μL PBS) in Dunkin-Hartley guinea pigs were estimated after a week's daily treatment with 30–300 mg kg−1 HIE, 30 mg kg−1 prednisolone, 10 mg kg−1 chlorpheniramine, or 10 mL kg−1 PBS. Ovalbumin-specific IgG and IgE and total IgE in serum were estimated using Enzyme-Linked Immunosorbent Assay. Histopathological assessment of the exenterated conjunctivae was also performed. The 30 and 300 mg kg−1 HIE treatment resulted in a significantly (p ≤ 0.001) low clinical score of allergic conjunctivitis. Ovalbumin-specific IgG and IgE as well as total serum IgE also decreased significantly (p ≤ 0.01–0.001). The conjunctival tissue in HIE treated guinea pigs had mild mononuclear infiltration compared to the PBS-treated ones, which had intense conjunctival tissue inflammatory infiltration. HIE exhibited antiallergic effect possibly by immunomodulation or immunosuppression. PMID:26681960

  9. Spatio-Temporal Variation in Predation by Urban Domestic Cats (Felis catus) and the Acceptability of Possible Management Actions in the UK

    PubMed Central

    Thomas, Rebecca L.; Fellowes, Mark D. E.; Baker, Philip J.

    2012-01-01

    Urban domestic cat (Felis catus) populations can attain exceedingly high densities and are not limited by natural prey availability. This has generated concerns that they may negatively affect prey populations, leading to calls for management. We enlisted cat-owners to record prey returned home to estimate patterns of predation by free-roaming pets in different localities within the town of Reading, UK and questionnaire surveys were used to quantify attitudes to different possible management strategies. Prey return rates were highly variable: only 20% of cats returned ≥4 dead prey annually. Consequently, approximately 65% of owners received no prey in a given season, but this declined to 22% after eight seasons. The estimated mean predation rate was 18.3 prey cat−1 year−1 but this varied markedly both spatially and temporally: per capita predation rates declined with increasing cat density. Comparisons with estimates of the density of six common bird prey species indicated that cats killed numbers equivalent to adult density on c. 39% of occasions. Population modeling studies suggest that such predation rates could significantly reduce the size of local bird populations for common urban species. Conversely, most urban residents did not consider cat predation to be a significant problem. Collar-mounted anti-predation devices were the only management action acceptable to the majority of urban residents (65%), but were less acceptable to cat-owners because of perceived risks to their pets; only 24% of cats were fitted with such devices. Overall, cat predation did appear to be of sufficient magnitude to affect some prey populations, although further investigation of some key aspects of cat predation is warranted. Management of the predation behavior of urban cat populations in the UK is likely to be challenging and achieving this would require considerable engagement with cat owners. PMID:23173057

  10. Enhanced lysis of (/sup 125/I)5-iodo-2'-deoxyuridine-labeled target cells in the presence of normal macrophages: possible mechanisms of action

    SciTech Connect

    Evans, R.; Eidlen, D.M.

    1985-01-01

    The potential mechanisms involved during the faster release of (/sup 125/I)-iodo-2'-deoxyuridine (/sup 125/IdUrd)-labeled target sarcoma cells in the presence of normal C57BL/6J peritoneal macrophages were investigated. Maximum (. 90%) spontaneous release of /sup 125/I from target cells cultured alone occurred over a period of about 10 days. However, after about 3 days, confluent sheets of target cells developed. In the presence of normal macrophages, 90% of the /sup 125/I was released between 3 and 7 days, again with the formation of confluent sheets of target cells. This enhanced /sup 125/I release was not influenced by increasing the relative concentration of IdUrd using the nonradioactive isotope 127IdUrd. Established mechanisms of target cell destruction were investigated but no evidence was found for the involvement of superoxide anion, hydrogen peroxide, or regulation by prostaglandin synthesis. The macrophage-mediated effect was abrogated by incorporating hydrocortisone-acetate (10(-7) to 10(-4) M) into the culture medium but this did not affect target cell proliferation. The use of serum-free culture medium suggested that macrophages secreted a soluble mediator that was not derived from or dependent on the presence of fetal bovine serum. In addition, macrophage-conditioned medium was able to induce the faster /sup 125/I release. The failure to precipitate with 20% trichloroacetic acid the /sup 125/I released from target cells cultured in the presence of macrophages indicated that the radioactive component had been separated from the precipitable DNA. The data are discussed in light of two possible hypotheses: that macrophages recognized subtle changes in IdUrd-labeled cells and exacerbate radiotoxicity, and that the faster release reflected proliferative death caused by stimulated growth.

  11. Transcriptional and Proteomic Analysis of a Ferric Uptake Regulator (Fur) Mutant of Shewanella oneidensis: Possible Involvement of Fur in Energy Metabolism, Transcriptional Regulation, and Oxidative Stress

    PubMed Central

    Thompson, Dorothea K.; Beliaev, Alexander S.; Giometti, Carol S.; Tollaksen, Sandra L.; Khare, Tripti; Lies, Douglas P.; Nealson, Kenneth H.; Lim, Hanjo; Yates III, John; Brandt, Craig C.; Tiedje, James M.; Zhou, Jizhong

    2002-01-01

    The iron-directed, coordinate regulation of genes depends on the fur (ferric uptake regulator) gene product, which acts as an iron-responsive, transcriptional repressor protein. To investigate the biological function of a fur homolog in the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1, a fur knockout strain (FUR1) was generated by suicide plasmid integration into this gene and characterized using phenotype assays, DNA microarrays containing 691 arrayed genes, and two-dimensional polyacrylamide gel electrophoresis. Physiological studies indicated that FUR1 was similar to the wild-type strain when they were compared for anaerobic growth and reduction of various electron acceptors. Transcription profiling, however, revealed that genes with predicted functions in electron transport, energy metabolism, transcriptional regulation, and oxidative stress protection were either repressed (ccoNQ, etrA, cytochrome b and c maturation-encoding genes, qor, yiaY, sodB, rpoH, phoB, and chvI) or induced (yggW, pdhC, prpC, aceE, fdhD, and ppc) in the fur mutant. Disruption of fur also resulted in derepression of genes (hxuC, alcC, fhuA, hemR, irgA, and ompW) putatively involved in iron uptake. This agreed with the finding that the fur mutant produced threefold-higher levels of siderophore than the wild-type strain under conditions of sufficient iron. Analysis of a subset of the FUR1 proteome (i.e., primarily soluble cytoplasmic and periplasmic proteins) indicated that 11 major protein species reproducibly showed significant (P < 0.05) differences in abundance relative to the wild type. Protein identification using mass spectrometry indicated that the expression of two of these proteins (SodB and AlcC) correlated with the microarray data. These results suggest a possible regulatory role of S. oneidensis MR-1 Fur in energy metabolism that extends the traditional model of Fur as a negative regulator of iron acquisition systems. PMID:11823232

  12. Reducing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on alcohol self-administration in rats: Possible involvement of the GABAB receptor.

    PubMed

    Maccioni, Paola; Lorrai, Irene; Carai, Mauro A M; Riva, Antonella; Morazzoni, Paolo; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-05-16

    Recent studies demonstrated that treatment with saikosaponin A (SSA) - an active ingredient of the medicinal herb, Bupleurum falcatum L. - selectively suppressed, likely via a GABAB receptor-mediated mechanism, intravenous self-administration of morphine and cocaine in rats [Yoon et al., 2012; 2013]. The present study was designed to investigate whether the capacity of SSA to suppress morphine and cocaine self-administration extends to oral alcohol self-administration. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were trained to lever-respond on a Fixed Ratio (FR) 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested under the FR4 (measure of alcohol reinforcing properties) and Progressive Ratio (PR; measure of alcohol motivational properties) schedules of reinforcement. The possible involvement of the GABAB receptor system was investigated testing the effect of (a) pretreatment with the GABAB receptor antagonist, SCH50911, and (b) combined treatment with the positive allosteric modulator of the GABAB receptor, GS39783. Treatment with SSA (0, 0.25, 0.5, and 1mg/kg, i.p.) markedly reduced lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). Pretreatment with 2mg/kg SCH50911 (i.p.) resulted in a partial blockade of the reducing effect of 0.5mg/kg SSA on lever-responding for alcohol and amount of self-administered alcohol. Combination of per se ineffective doses of GS39783 (5mg/kg, i.g.) and SSA (0.1mg/kg, i.p.) reduced lever-responding for alcohol and amount of self-administered alcohol. These results (a) extend to alcohol self-administration the capacity of SSA to suppress morphine and cocaine self-administration in rats and (b) suggest that the GABAB receptor system is likely part of the neural substrate underlying the reducing effect of SSA on

  13. Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

    SciTech Connect

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa

    2013-07-01

    Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

  14. Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy

    PubMed Central

    Schaerlinger, B; Hickel, P; Etienne, N; Guesnier, L; Maroteaux, L

    2003-01-01

    The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT2 subtype. To elucidate if 5-HT2 receptors (5-HT2Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8′-hydroxy-DHE (8′-OH-DHE) at the 5-HT2B and 5-HT2CRs by binding, inositol triphosphate (IP3) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. DHE and 8′-OH-DHE are competitive compounds at 5-HT2B and 5-HT2CRs. 8′-OH-DHE interaction at (5-HT2BRs) was best fitted by a biphasic competition curve and displayed the highest affinity with a Ki of 5 nM. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC50 of 8.32±0.09 for 8′-OH-DHE at 5-HT2B and 7.83±0.06 at 5-HT2CRs. Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8′-OH-DHE. The number of 5-HT2BR-binding sites was always more affected than 5-HT2CRs. At 5-HT2BRs, 8′-OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP3 or cGMP. By contrast, the 5-HT2CR coupling was reversible after either treatment. Chronic exposure to 8′-OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT2B, but not 5-HT2CRs. This may be of relevance to therapeutic actions of the compound. PMID:12970106

  15. Nodes-and-connections RNAi knockdown screening: identification of a signaling molecule network involved in fulvestrant action and breast cancer prognosis

    PubMed Central

    Miyoshi, N; Wittner, B S; Shioda, K; Hitora, T; Ito, T; Ramaswamy, S; Isselbacher, K J; Sgroi, D C; Shioda, T

    2015-01-01

    Although RNA interference (RNAi) knockdown screening of cancer cell cultures is an effective approach to predict drug targets or therapeutic/prognostic biomarkers, interactions among identified targets often remain obscure. Here, we introduce the nodes-and-connections RNAi knockdown screening that generates a map of target interactions through systematic iterations of in silico prediction of targets and their experimental validation. An initial RNAi knockdown screening of MCF-7 human breast cancer cells targeting 6560 proteins identified four signaling molecules required for their fulvestrant-induced apoptosis. Signaling molecules physically or functionally interacting with these four primary node targets were computationally predicted and experimentally validated, resulting in identification of four second-generation nodes. Three rounds of further iterations of the prediction–validation cycle generated third, fourth and fifth generation of nodes, completing a 19-node interaction map that contained three predicted nodes but without experimental validation because of technical limitations. The interaction map involved all three members of the death-associated protein kinases (DAPKs) as well as their upstream and downstream signaling molecules (calmodulins and myosin light chain kinases), suggesting that DAPKs play critical roles in the cytocidal action of fulvestrant. The in silico Kaplan–Meier analysis of previously reported human breast cancer cohorts demonstrated significant prognostic predictive power for five of the experimentally validated nodes and for three of the prediction-only nodes. Immunohistochemical studies on the expression of 10 nodal proteins in human breast cancer tissues not only supported their prognostic prediction power but also provided statistically significant evidence of their synchronized expression, implying functional interactions among these nodal proteins. Thus, the Nodes-and-Connections approach to RNAi knockdown screening yields

  16. Involvement of neurotransmitters in the action of the nociceptin/orphanin FQ peptide-receptor system on passive avoidance learning in rats.

    PubMed

    Palotai, Miklós; Adamik, Agnes; Telegdy, Gyula

    2014-08-01

    The nociceptin/orphanin FQ peptide (NOP) receptor and its endogenous ligand plays role in several physiologic functions of the central nervous system, including pain, locomotion, anxiety and depression, reward and drug addiction, learning and memory. Previous studies demonstrated that the NOP-receptor system induces impairment in memory and learning. However, we have little evidence about the underlying neuromodulation. The aim of the present study was to investigate the involvement of distinct neurotransmitters in the action of the selective NOP receptor agonist orphan G protein-coupled receptor (GPCR) SP9155 P550 on memory consolidation in a passive avoidance learning test in rats. Accordingly, rats were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a nonselective opioid receptor antagonist, naloxone, a non-specific nitric oxide synthase inhibitor, nitro-L-arginine, a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol. Atropine, bicuculline, naloxone and phenoxybenzamine reversed the orphan GPCR SP9155 P550-induced memory impairment, whereas propranolol, haloperidol and nitro-L-arginine were ineffective. Our results suggest that the NOP system-induced impairment of memory consolidation is mediated through muscarinic cholinergic, GABA-A-ergic, opioid and α-adrenergic receptors, whereas β-adrenergic, D2, D3, D4-dopaminergic and nitrergic mechanisms are not be implicated. PMID:24893797

  17. Mode of action analysis for pesticide-induced rodent liver tumours involving activation of the constitutive androstane receptor: relevance to human cancer risk.

    PubMed

    Lake, Brian G; Price, Roger J; Osimitz, Thomas G

    2015-06-01

    A number of non-genotoxic chemicals, including some pesticides, have been shown to increase the incidence of liver tumours in rats and/or mice. Frameworks for analysing the modes of action (MOAs) by which chemicals produce liver tumours in rodents and the relevance of such tumour data for human risk assessment have now been established. One common MOA for rodent liver tumour formation by non-genotoxic chemicals involves activation of the constitutive androstane receptor (CAR). Key and associative events for a CAR-activation MOA include receptor activation, liver hypertrophy, induction of cytochrome P450 enzyme activities, increased replicative DNA synthesis, altered hepatic foci and liver tumours. While some effects of rodent CAR activators can be observed in human liver, a major species difference is that, unlike rodents, CAR activators do not increase replicative DNA synthesis in human hepatocytes. The CAR-activation MOA for rodent liver tumour formation is thus not plausible for humans, and hence such compounds do not pose a hepatocarcinogenic hazard for humans. PMID:25045103

  18. Systems Analysis of Immune Responses in Marek's Disease Virus-Infected Chickens Identifies a Gene Involved in Susceptibility and Highlights a Possible Novel Pathogenicity Mechanism▿†

    PubMed Central

    Smith, Jacqueline; Sadeyen, Jean-Remy; Paton, Ian R.; Hocking, Paul M.; Salmon, Nigel; Fife, Mark; Nair, Venugopal; Burt, David W.; Kaiser, Pete

    2011-01-01

    Marek's disease virus (MDV) is a highly contagious oncogenic alphaherpesvirus that causes disease that is both a cancer model and a continuing threat to the world's poultry industry. This comprehensive gene expression study analyzes the host response to infection in both resistant and susceptible lines of chickens and inherent expression differences between the two lines following the infection of the host. A novel pathogenicity mechanism, involving the downregulation of genes containing HIC1 transcription factor binding sites as early as 4 days postinfection, was suggested from this analysis. HIC1 drives antitumor mechanisms, suggesting that MDV infection switches off genes involved in antitumor regulation several days before the expression of the MDV oncogene meq. The comparison of the gene expression data to previous QTL data identified several genes as candidates for involvement in resistance to MD. One of these genes, IRG1, was confirmed by single nucleotide polymorphism analysis to be involved in susceptibility. Its precise mechanism remains to be elucidated, although the analysis of gene expression data suggests it has a role in apoptosis. Understanding which genes are involved in susceptibility/resistance to MD and defining the pathological mechanisms of the disease gives us a much greater ability to try to reduce the incidence of this virus, which is costly to the poultry industry in terms of both animal welfare and economics. PMID:21865384

  19. Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages.

    PubMed

    Bae, Young-An; Cheon, Hyae Gyeong

    2016-07-01

    Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction. PMID:27382358

  20. Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages

    PubMed Central

    Bae, Young-An

    2016-01-01

    Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction. PMID:27382358

  1. Involvement of Receptor Activity-Modifying Protein 3 (RAMP3) in the Vascular Actions of Adrenomedullin in Rat Mesenteric Artery Smooth Muscle Cells.

    PubMed

    Chauhan, Madhu; Yallampalli, Uma; Banadakappa, Manu; Yallampalli, Chandrasekhar

    2015-11-01

    CALCB, ADM, and ADM2 are potent vasodilators that share a seven-transmembrane GPCR, calcitonin receptor-like receptor (CALCRL), whose ligand specificity is dictated by the presence of one of the three receptor activity-modifying proteins (RAMPs). We assessed the relative pharmacologic potency of these peptides in mesenteric artery smooth muscle cells (VSMCs) and the specific RAMP that mediates the effect of ADM in VSMCs. VSMCs, with or without RAMP knockdown, were treated with CALCB, ADM, or ADM2 in the presence or absence of their antagonists, CALCB8-37, ADM22-52, and ADM217-47, respectively, to assess the relative effect of peptides on cAMP production and their pharmacologic potency. Proximity ligation assay was used to assess the specific RAMP that associates with CALCRL to mediate the actions of ADM in VSMCs. All three peptides induced cAMP generation in VSMCs and the order of their potency is CALCB > ADM > ADM2. Effects of CALCB were blocked by CALCB8-37, ADM effects were blocked by CALCB8-37 and ADM217-47 but not ADM22-52, and ADM2 effects were blocked by all three antagonists. Knockdown of RAMP2 was ineffective, whereas knockdown of RAMP3 inhibited ADM-induced cAMP production in VSMCs, suggesting involvement of RAMP3 with CALCRL to mediate ADM effects. Absence of both RAMP2 and RAMP3 further increased CALCB-induced cAMP synthesis compared to control (P < 0.05). ADM increased CALCRL and RAMP3 association and RAMP3 knockdown inhibited the interaction of ADM with CALCRL. PMID:26423127

  2. The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: A study in a rat model of moderate and relatively high human exposure

    SciTech Connect

    Brzoska, Malgorzata M. Rogalska, Joanna; Kupraszewicz, Elzbieta

    2011-02-01

    It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H{sub 2}O{sub 2}), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50 mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50 mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H{sub 2}O{sub 2} and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress.

  3. The Global Possible: Resources, Development, and the New Century. The Statement and Action Agenda of an International Conference (Washington, D.C., May 2-5, 1984).

    ERIC Educational Resources Information Center

    World Resources Inst., Washington, DC.

    The relationships between earth's resources and the human future and the challenges of maintaining a sustainable environment were probed at an international conference sponsored by the World Resources Institute. A synthesis of the conference's reports, perspectives, and plans for action are presented in this document. The position supported by the…

  4. Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

    PubMed Central

    Barış, İkbal Cansu; Caner, Vildan; Şen Türk, Nilay; Sarı, İsmail; Hacıoğlu, Sibel; Doğu, Mehmet Hilmi; Çetin, Ozan; Tepeli, Emre; Can, Özge; Bağcı, Gülseren; Keskin, Ali

    2015-01-01

    Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. Materials and Methods: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. Results: GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040). Conclusion: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ. PMID:25912017

  5. Possible involvement of nitrergic and opioidergic systems in the modulatory effect of acute chloroquine treatment on pentylenetetrazol induced convulsions in mice.

    PubMed

    Hassanipour, Mahsa; Shirzadian, Armin; Boojar, Mahdi Mashhadi-Akbar; Abkhoo, Aminreza; Abkhoo, Alireza; Delazar, Sina; Amiri, Shayan; Rahimi, Nastaran; Ostadhadi, Sattar; Dehpour, Ahmad-Reza

    2016-03-01

    Chloroquine has long been used for the treatment of malaria and rheumatological disorders. Accumulating evidence suggests potential use of chloroquine as a neuroprotective agent. Several studies have reported that endogenous opioids and nitric oxide (NO) system mediate the chloroquine effects. In the present study, the involvements of endogenous opioids and NO in the modulatory effects of chloroquine on pentylenetetrazol-induced seizures were assessed in mice. Chloroquine 5mg/kg significantly increased the seizure threshold, but this effect was reversed with naltrexone 1mg/kg. Acute co-administration of l-NAME (non-selective NO synthase (NOS) inhibitor, 5mg/kg) or 7-NI (selective neuronal NOS inhibitor, 40mg/kg) with the effective dose of chloroquine completely inhibited its anticonvulsant effects. Acute single injection of a sub-effective dose of l-arginine (NO precursor, 60mg/kg) with a sub-effective dose of chloroquine 2.5mg/kg increased the seizure threshold but administration of l-arginine 60mg/kg with chloroquine 10mg/kg decreased the seizure threshold. Moreover, the combination of the lower doses of naltrexone (0.1mg/kg) and 7-NI (15mg/kg) showed additive effects in blocking the chloroquine-induced anticonvulsant properties. Chloroquine 5mg/kg enhanced the hippocampal nitrite levels. Chloroquine at the dose of 20mg/kg decreased the seizure threshold. This effect was inhibited through l-NAME (5mg/kg), 7-NI (40mg/kg) and naltrexone (1mg/kg) administration with this dose of chloroquine. In conclusion, NO signaling probably through neuronal NOS, but not inducible NOS could be involved in the opioid-dependent anticonvulsant effects of chloroquine in this model of seizures in mice. It seems that nitric oxide and opioid systems are involved in modulatory effect of chloroquine on seizures induced by pentylenetetrazol. PMID:26655695

  6. Possible involvement of toluene-2,3-dioxygenase in defluorination of 3-fluoro-substituted benzenes by toluene-degrading Pseudomonas sp. strain T-12

    SciTech Connect

    Renganathan, V. )

    1989-02-01

    Pseudomonas sp. strain T-12 cells in which the toluene-degradative pathway enzymes have been induced can transform many 3-fluoro-substituted benzenes to the corresponding 2,3-catechols with simultaneous elimination of the fluorine substituent as inorganic fluoride. Substrates for this transformation included 3-fluorotoluen, 3-fluorotrifluorotuluene, 3-fluorohalobenzenes, 3-fluoroanisole, and 3-fluorobenzonitrile. While 3-fluorotoluene and 3-fluoroaniole produced only defluorinated catechols, other substrates generated catechol products with and without the fluorine substituent. The steric size of the C-1 substituent affected the ratio of defluorinated to fluorinated catechols formed from a substrate. A mechanism for the defluorination reaction involving toluene-2,3-dioxygenase is proposed.

  7. Molecular characterisation and chromosomal mapping of transcripts having tissue-specific expression in the malaria mosquito Anopheles gambiae: possible involvement in visual or olfactory processes.

    PubMed

    Ricci, Irene; Santolamazza, Federica; Costantini, Carlo; Favia, Guido

    2002-01-01

    We have compared the transcriptional activity of heads, antennae + palps, and carcasses in the mosquito Anopheles gambiae by means of differential display PCR (DD-PCR). Three transcripts specifically or preferentially expressed in the heads and in the antennae + palps have been selected. All are very similar to genes related to visual and olfactory mechanisms of several different organisms. They have been named Ag arrestin, Ag rLDL, and Ag dynamin. The potential of the DD-PCR technique in identifying genes involved in mosquito behaviour and the usefulness of the molecular characterisation of these transcripts are discussed. PMID:11822731

  8. Effects of Controlled Atmospheres on Production of Sesquiterpenoid Stress Metabolites by White Potato Tuber: Possible Involvement of Cyanide-resistant Respiration.

    PubMed

    Alves, L M; Heisler, E G; Kissinger, J C; Patterson, J M; Kalan, E B

    1979-02-01

    Levels of katahdinone (solavetivone), lubimin, rishitin, and phytuberin, sesquiterpenoid stress metabolites of white potato (Solanum tuberosum), were monitored in tuber slices which were challenged with an extract of Phytophthora infestans and incubated under controlled atmospheres. A mixture of ethylene in air enhanced stress metabolite production. This enhancement was amplified by higher partial pressures of oxygen. Stress metabolite production was inhibited by salicylhydroxamic acid. These results suggest the involvement of cyanide-resistant respiration in the production of potato stress metabolites, compounds which may serve as phytoalexins. PMID:16660728

  9. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.

    PubMed

    Yu, Jing; Eto, Masato; Akishita, Masahiro; Kaneko, Akiyo; Ouchi, Yasuyoshi; Okabe, Tetsuro

    2007-02-16

    Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells. PMID:17196933

  10. H. R. 3124: A bill to require the Secretary of Transportation to take actions to protect against railroad accidents involving hazardous materials, introduced in the US House of Representatives, One Hundred Second Congress, First Session, July 31, 1991

    SciTech Connect

    Not Available

    1991-01-01

    This bill was introduced into the US House of Representatives on July 31, 1991 to require the Secretary of Transportation to take actions to protect against railroad accidents involving hazardous materials. One of the main aspects of this legislation is to identify railroad routes which present the greatest danger of accidents and to find alternative routes.

  11. Possible involvement of sulfotransferase 1A1 in estragole-induced DNA modification and carcinogenesis in the livers of female mice.

    PubMed

    Suzuki, Yuta; Umemura, Takashi; Ishii, Yuji; Hibi, Daisuke; Inoue, Tomoki; Jin, Meilan; Sakai, Hiroki; Kodama, Yukio; Nohmi, Takehiko; Yanai, Tokuma; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2012-12-12

    Estragole (ES), a natural organic compound, is frequently used as a flavoring in food even though it is a hepatocarcinogen in mice. Although formation of ES-specific DNA adducts following conversion from ES to the nucleophilic metabolite by sulfotransferase 1A1 (SULT1A1) has been reported, the modes of action underlying ES-induced hepatocarcinogenesis remain uncertain because conventional genotoxicity tests for ES yield negative results. In the present study, taking notice of the fact that there is a sex difference in SULT1A1 activity in the mouse liver, we assessed the frequency of micronuclei in polychromatic erythrocytes and the mutant frequency (MF) of reporter genes in female gpt delta mice treated with ES at doses of 0 (corn oil), 37.5, 75, 150 or 300mg/kg body weight (bw) by gavage for 13 weeks. Results were compared with those obtained in males. Since one female was found dead at week one, the highest dose was reduced to 250mg/kg bw in females from week two. As reported previously in C57BL/6 mice, the mRNA levels of Sult1a1 in female gpt delta mice were significantly higher than those in the males. The levels of ES-specific DNA adducts in the females were higher than those in the males at all doses except the highest dose. In addition, MFs of the gpt gene were significantly increased from doses of 75mg/kg bw of females, but the increment was observed only at the highest dose in males. There were no changes in the micronucleus test among the groups. Thus, the overall data suggest that specific DNA modifications by the SULT1A1-mediated carbocation formation and the resultant genotoxicity are key events in the early stage of ES-induced hepatocarcinogenesis of mice. PMID:22885592

  12. Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1.

    PubMed

    Yamashita, Atsushi; Kumazawa, Tsukasa; Koga, Hiroki; Suzuki, Naotaka; Oka, Saori; Sugiura, Takayuki

    2010-07-01

    GPR55 is a seven-transmembrane G-protein-coupled receptor that has been proposed as a novel type of cannabinoid receptor. Previously, we identified lysophosphatidylinositol (LPI), in particular 2-arachidonoyl-LPI, as an agonist for GPR55. In the present study, we examined whether intracellular phospholipase A1 (DDHD domain containing 1, or DDHD1), previously identified as phosphatidic acid (PA)-preferring PLA1 (PA-PLA1), is involved in the formation of 2-arachidonoyl-LPI. HEK293 cells expressing DDHD1 produced [(3)H]arachidonic acid-containing LPI after prelabeling with [(3)H]arachidonic acid and subsequent activation by ionomycin; the formation of [(3)H]LPI was inhibited by n-butanol and the overexpression of an inactive PLD1 mutant PLD1K898R. DDHD1 was translocated from the cytosol to membranes upon ionomycin treatment. A purified recombinant DDHD1 formed [(3)H]LPI when incubated with [(3)H]PI; the V(max) and apparent K(m) were 190 micromol/min/mg protein and 10 mol% PI, respectively. DDHD1 binds PA, and the addition of PA to DDHD1 increased the affinity for PI (K(m) ; 3 mol%) and augmented the PI-PLA1 activity. DDHD1 activated by PA was returned to a basal state by its own PA-hydrolytic activity. These results implicate DDHD1 in the formation of 2-arachidonoyl-LPI and indicate that the process is modulated by PA released by phospholipase D. Similar observations for the production of arachidonic acid-containing LPI in neuroblastoma cells suggest the DDHD1-LPI-GPR55 axis to be involved in functions in the brain. PMID:20359546

  13. Identification of domains on the extrinsic 23 kDa protein possibly involved in electrostatic interaction with the extrinsic 33 kDa protein in spinach photosystem II.

    PubMed

    Tohri, Akihiko; Dohmae, Naoshi; Suzuki, Takehiro; Ohta, Hisataka; Inoue, Yasunori; Enami, Isao

    2004-03-01

    To elucidate the domains on the extrinsic 23 kDa protein involved in electrostatic interaction with the extrinsic 33 kDa protein in spinach photosystem II, we modified amino or carboxyl groups of the 23 kDa protein to uncharged methyl ester groups with N-succinimidyl propionate or glycine methyl ester in the presence of a water-soluble carbodiimide, respectively. The N-succinimidyl propionate-modified 23 kDa protein did not bind to the 33 kDa protein associated with PSII membranes, whereas the glycine methyl ester-modified 23 kDa protein completely bound. This indicates that positive charges on the 23 kDa protein are important for electrostatic interaction with the 33 kDa protein associated with the PSII membranes. Mapping of the N-succinimidyl propionate-modified sites of the 23 kDa protein was performed using Staphylococcus V8 protease digestion of the modified protein followed by determination of the mass of the resultant peptide fragments with MALDI-TOF MS. The results showed that six domains (Lys11-Lys14, Lys27-Lys38, Lys40, Lys90-Lys96, Lys143-Lys152, Lys166-Lys174) were modified with N-succinimidyl propionate. In these domains, Lys11, Lys13, Lys33, Lys38, Lys143, Lys166, Lys170 and Lys174 were wholly conserved in the 23 kDa protein from 12 species of higher plants. These positively charged lysyl residues on the 23 kDa protein may be involved in electrostatic interactions with the negatively charged carboxyl groups on the 33 kDa protein, the latter has been suggested to be important for the 23 kDa binding [Bricker, T.M. & Frankel, L.K. (2003) Biochemistry42, 2056-2061]. PMID:15009208

  14. Possible involvement of the long terminal repeat of transposable element 17.6 in regulating expression of an insecticide resistance-associated P450 gene in Drosophila.

    PubMed Central

    Waters, L C; Zelhof, A C; Shaw, B J; Ch'ang, L Y

    1992-01-01

    P450-A and P450-B are electrophoretically defined subsets of cytochrome P450 enzymes in Drosophila melanogaster. P450-A is present among all strains tested, whereas expression of P450-B is associated with resistance to insecticides. Monoclonal antibodies were used to obtain cDNA clones for an enzyme from each P450 subset (i.e., P450-A1 and P450-B1). The P450-B1 cDNA was sequenced and shown to code for a P450 of 507 amino acids. Its gene has been named CYP6A2. Comparative molecular analyses of a pair of susceptible, 91-C, and resistant, 91-R, Drosophila strains were made. There was 20-30 times more P450-B1 mRNA in 91-R than in 91-C, and the small amount of P450-B1 mRNA in 91-C was significantly larger in size than that in 91-R. The P450-B1 gene in 91-R was structurally different from that in 91-C but was not amplified. The P450-B1 gene in 91-C contained a solitary long terminal repeat of transposable element 17.6 in its 3' untranslated region. It was absent in the P450-B1 gene of 91-R. On the basis of features of the long terminal repeat and its location in the gene of the susceptible fly, we propose that a posttranscriptional mechanism involving mRNA stability could be involved in regulating P450-B1 gene expression. Images PMID:1317576

  15. Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis

    SciTech Connect

    Gericke, G.S.; Simonic, I.; Cloete, E.; Buckle, C.

    1995-10-09

    Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites. 32 refs., 1 tab.

  16. Involvement of medial prefrontal cortex alpha-2 adrenoceptors on memory acquisition deficit induced by arachidonylcyclopropylamide, a cannabinoid CB1 receptor agonist, in rats; possible involvement of Ca2+ channels.

    PubMed

    Beiranvand, Afsaneh; Nasehi, Mohammad; Zarrindast, Mohammad-Reza; Moghaddasi, Mehrnoush

    2016-09-01

    Functional interactions between cannabinoid and alpha-2 adrenergic systems in cognitive control in the medial prefrontal cortex (mPFC) seem possible. The present study evaluated the possible role of alpha-2 adrenoceptors of the prefrontal cortex on effect of arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor (CB1R) agonist, in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the mPFC, trained in a step-through task, and tested 24 h after training to measure step-through latency. Results indicate that pre-training microinjection of ACPA (0.05 and 0.5 μg/rat) and clonidine (alpha-2 adrenoceptor agonist; 1 and 2 μg/rat) reduce memory acquisition. Pre-training subthreshold dose of clonidine (0.5 µg/rat) restored memory-impairing effect of ACPA (0.05 and 0.5 µg/rat). On the other hand, pre-training administration of the alpha-2 adrenoceptor antagonist yohimbine in all doses used (0.5, 1, and 2 μg/rat) did not affect memory acquisition by itself, while a subthreshold dose of yohimbine (2 µg/rat) potentiated memory impairment induced by ACPA (0.005 µg/rat). Finally, a subthreshold dose of SKF96365 (a Ca(2+) channel blocker) blocked clonidine and yohimbine effect of memory responses induced by ACPA. In conclusion, these data indicate that mPFC alpha-2 adrenoceptors play an important role in ACPA-induced amnesia and Ca(2+) channels have a critical role this phenomenon. PMID:27317021

  17. Antihyperglycemic effect of Annona squamosa hexane extract in type 2 diabetes animal model: PTP1B inhibition, a possible mechanism of action?

    PubMed Central

    Davis, Joseph Alex; Sharma, Suchitra; Mittra, Shivani; Sujatha, S.; Kanaujia, Anil; Shukla, Gyanesh; Katiyar, Chandrakant; Lakshmi, B.S.; Bansal, Vinay Sheel; Bhatnagar, Pradip Kumar

    2012-01-01

    Aim: The mechanism of action of Annona squamosa hexane extract in mediating antihyperglycemic and antitriglyceridimic effect were investigated in this study. Materials and Methods: The effects of extract on glucose uptake, insulin receptor-β (IR-β), insulin receptor substrate-1 (IRS-1) phosphorylation and glucose transporter type 4 (GLUT4) and phosphoinositide 3-kinase (PI3 kinase) mRNA expression were studied in L6 myotubes. The in vitro mechanism of action was tested in protein-tyrosine phosphatase 1B (PTP1B), G-protein-coupled receptor 40 (GPR40), silent mating type information regulation 2 homolog 1 (SIRT1) and dipeptidyl peptidase-IV (DPP-IV) assays. The in vivo efficacy was characterized in ob/ob mice after an oral administration of the extract for 21 days. Results: The effect of extract promoted glucose uptake, IR-β and IRS-1 phosphorylation and GLUT4 and PI3 kinase mRNA upregulation in L6 myotubes. The extract inhibited PTP1B with an IC50 17.4 μg/ml and did not modulate GPR40, SIRT1 or DPP-IV activities. An oral administration of extract in ob/ob mice for 21 days improved random blood glucose, triglyceride and oral glucose tolerance. Further, the extract did not result in body weight gain before and after treatment (29.3 vs. 33.6 g) compared to rosiglitazone where significant body weight gain was observed (28.4 vs. 44.5 g; *P<0.05 after treatment compared to before treatment). Conclusion: The results suggest that Annona squamosa hexane extract exerts its action by modulating insulin signaling through inhibition of PTP1B. PMID:22701240

  18. Identification of a novel aminopeptidase P-like gene (OnAPP) possibly involved in Bt toxicity and resistance in a major corn pest (Ostrinia nubilalis).

    PubMed

    Khajuria, Chitvan; Buschman, Lawrent L; Chen, Ming-Shun; Siegfried, Blair D; Zhu, Kun Yan

    2011-01-01

    Studies to understand the Bacillus thuringiensis (Bt) resistance mechanism in European corn borer (ECB, Ostrinia nubilalis) suggest that resistance may be due to changes in the midgut-specific Bt toxin receptor. In this study, we identified 10 aminopeptidase-like genes, which have previously been identified as putative Bt toxin receptors in other insects and examined their expression in relation to Cry1Ab toxicity and resistance. Expression analysis for the 10 aminopeptidase-like genes revealed that most of these genes were expressed predominantly in the larval midgut, but there was no difference in the expression of these genes in Cry1Ab resistant and susceptible strains. This suggested that altered expression of these genes was unlikely to be responsible for resistance in these ECB strains. However, we found that there were changes in two amino acid residues of the aminopeptidase-P like gene (OnAPP) involving Glu(305) to Lys(305) and Arg(307) to Leu(307) in the two Cry1Ab-resistant strains as compared with three Cry1Ab-susceptible strains. The mature OnAPP contains 682 amino acid residues and has a putative signal peptide at the N-terminus, a predicted glycosylphosphatidyl-inositol (GPI)-anchor signal at the C-terminal, three predicted N-glycosylation sites at residues N178, N278 and N417, and an O-glycosylation site at residue T653. We used a feeding based-RNA interference assay to examine the role of the OnAPP gene in Cry1Ab toxicity and resistance. Bioassays of Cry1Ab in larvae fed diet containing OnAPP dsRNA resulted in a 38% reduction in the transcript level of OnAPP and a 25% reduction in the susceptibility to Cry1Ab as compared with larvae fed GFP dsRNA or water. These results strongly suggest that the OnAPP gene could be involved in binding the Cry1Ab toxin in the ECB larval midgut and that mutations in this gene may be associated with Bt resistance in these two ECB strains. PMID:21887358

  19. Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal root ganglia - a possible explanation for peripheral nervous system involvement in Charcot-Marie-Tooth 2A.

    PubMed

    Kawalec, Maria; Zabłocka, Barbara; Kabzińska, Dagmara; Neska, Jacek; Beręsewicz, Małgorzata

    2014-01-01

    Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential for mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mutations in the mitofusin 2 gene cause axonal Charcot-Marie-Tooth type 2A (CMT2A), an inherited disease affecting peripheral nerve axons. The precise mechanism by which mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is a hypothesis suggesting the involvement of reduced expression of a homologous protein, mitofusin 1 (Mfn1), in the peripheral nervous system, and less effective compensation of defective mitofusin 2 by mitofusin 1. We therefore aimed to perform an analysis of the mitofusin 1 and mitofusin 2 mRNA and protein expression profiles in different mouse tissues, with special attention paid to dorsal root ganglia (DRGs), as parts of the peripheral nervous system. Quantitative measurement relating to mRNA revealed that expression of the Mfn2 gene dominates over Mfn1 mainly in mouse DRG, as opposed to other nervous system samples and other tissues studied. This result was further supported by Western blot evaluation. Both these sets of data confirm the hypothesis that the cellular consequences of mutations in the mitofusin 2 gene can mostly be manifested in the peripheral nervous system. PMID:25574749

  20. Possible involvement of CD10 in the development of endometriosis due to its inhibitory effects on CD44-dependent cell adhesion.

    PubMed

    Iwase, Akira; Kotani, Tomomi; Goto, Maki; Kobayashi, Hiroharu; Takikawa, Sachiko; Nakahara, Tatsuo; Nakamura, Tomoko; Kondo, Mika; Bayasula; Nagatomo, Yoshinari; Kikkawa, Fumitaka

    2014-01-01

    A reduced response to progesterone in the eutopic endometrium with endometriosis and in endometriotic tissues is considered to be the underlying factor for endometriosis. CD10 is known to be expressed by endometrial and endometriotic stromal cells and may be induced by progestins, although the function of CD10 is not fully revealed in endometrial or endometriotic tissues. In the current study, the expression of CD10 was significantly increased by treatment of the cells with progesterone, 17β-estradiol, and dibutyryl cyclic adenosine monophosphate (cAMP) in the endometrial stromal cells. On the other hand, the expression of CD10 following treatment with progesterone, 17β-estradiol, and dibutyryl cAMP was not significantly increased in endometriotic stromal cells. The adhesion assay for endometrial and endometriotic stromal cells to hyaluronan using 5- or 6-(N-succinimidyloxycarbonyl)-fluorescein 3', 6'-diacetate-labeled cells demonstrated that the CD44-dependent adhesion of stromal cells was inhibited by CD10. As far as the induction of CD10 is concerned, the effect of progesterone was different between endometrial stromal cells and endometriotic stromal cells. CD10 might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion. PMID:23653392

  1. Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression.

    PubMed

    Korita, Daizo; Sagawa, Norimasa; Itoh, Hiroaki; Yura, Shigeo; Yoshida, Masahiro; Kakui, Kazuyo; Takemura, Maki; Yokoyama, Chieko; Tanabe, Tadashi; Fujii, Shingo

    2002-11-01

    Prostacyclin (PGI(2)), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI(2) metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI(2) secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A(2), cyclooxygenase (COX)-1, COX-2, and prostacyclin synthase (PGIS) in the human uterine myometrium at various gestational ages before labor. To elucidate the involvement of labor in the increase in PGI(2) production during labor, we next examined the effect of labor-like cyclic mechanical stretch on PGI(2) production by cultured human myometrial cells. Pregnancy specifically increased COX-1 and PGIS protein expression in the myometrial tissues before labor (P < 0.01 for both). Cyclic mechanical stretch augmented PGIS promoter activity, via activation of activator protein-1 site, and PGIS mRNA and protein expression in cultured human myometrial cells and resulted in a 3.5-fold increase in the concentration of 6-keto-prostaglandin F(1alpha), the stable metabolite of PGI(2), in the culture medium (P < 0.05). However, stretch did not affect the levels of prostaglandin E(2), prostaglandin F(2alpha), or thromboxane A(2) secreted into the same culture media. These results suggest that cyclic mechanical stretch during labor may contribute to the increase in the PGI(2) concentration in the maternal plasma during parturition. PMID:12414894

  2. Cell cycle arrest induced by inhibitors of epigenetic modifications in maize (Zea mays) seedling leaves: characterization of the process and possible mechanisms involved.

    PubMed

    Wang, Pu; Zhang, Hao; Hou, Haoli; Wang, Qing; Li, Yingnan; Huang, Yan; Xie, Liangfu; Gao, Fei; He, Shibin; Li, Lijia

    2016-07-01

    Epigenetic modifications play crucial roles in the regulation of chromatin architecture and are involved in cell cycle progression, including mitosis and meiosis. To explore the relationship between epigenetic modifications and the cell cycle, we treated maize (Zea mays) seedlings with six different epigenetic modification-related inhibitors and identified the postsynthetic phase (G2 ) arrest via flow cytometry analysis. Total H4K5ac levels were significantly increased and the distribution of H3S10ph signalling was obviously changed in mitosis under various treatments. Further statistics of the cells in different periods of mitosis confirmed that the cell cycle was arrested at preprophase. Concentrations of hydrogen peroxide were relatively higher in the treated plants and the antioxidant thiourea could negate the influence of the inhibitors. Moreover, all of the treated plants displayed negative results in the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) and γ-H2AX immunostaining assays after exposure for 3 d. Additionally, the expression level of topoisomerase genes in the treated plants was relatively lower than that in the untreated plants. These results suggest that these inhibitors of epigenetic modifications could cause preprophase arrest via reactive oxygen species formation inhibiting the expression of DNA topoisomerase genes, accompanied by changes in the H4K5ac and H3S10ph histone modifications. PMID:27040740

  3. Cysteine dioxygenase and cysteine sulfinate decarboxylase genes of the deep-sea mussel Bathymodiolus septemdierum: possible involvement in hypotaurine synthesis and adaptation to hydrogen sulfide.

    PubMed

    Nagasaki, Toshihiro; Hongo, Yuki; Koito, Tomoko; Nakamura-Kusakabe, Ikumi; Shimamura, Shigeru; Takaki, Yoshihiro; Yoshida, Takao; Maruyama, Tadashi; Inoue, Koji

    2015-03-01

    It has been suggested that invertebrates inhabiting deep-sea hydrothermal vent areas use the sulfinic acid hypotaurine, a precursor of taurine, to protect against the toxicity of hydrogen sulfide contained in the seawater from the vent. In this protective system, hypotaurine is accumulated in the gill, the primary site of sulfide exposure. However, the pathway for hypotaurine synthesis in mollusks has not been identified. In this study, we screened for the mRNAs of enzymes involved in hypotaurine synthesis in the deep-sea mussel Bathymodiolus septemdierum and cloned cDNAs encoding cysteine dioxygenase and cysteine sulfinate decarboxylase. As mRNAs encoding cysteamine dioxygenase and cysteine lyase were not detected, the cysteine sulfinate pathway is suggested to be the major pathway of hypotaurine and taurine synthesis. The two genes were found to be expressed in all the tissues examined, but the gill exhibited the highest expression. The mRNA level in the gill was not significantly changed by exposure to sulfides or thiosulfate. These results suggests that the gill of B. septemdierum maintains high levels of expression of the two genes regardless of ambient sulfide level and accumulates hypotaurine continuously to protect against sudden exposure to high level of sulfide. PMID:25501502

  4. Aging decreases collagen IV expression in vivo in the dermo-epidermal junction and in vitro in dermal fibroblasts: possible involvement of TGF-β1.

    PubMed

    Feru, Jezabel; Delobbe, Etienne; Ramont, Laurent; Brassart, Bertrand; Terryn, Christine; Dupont-Deshorgue, Aurelie; Garbar, Christian; Monboisse, Jean-Claude; Maquart, Francois-Xavier; Brassart-Pasco, Sylvie

    2016-08-01

    Collagen IV is a major component of the dermo-epidermal junction (DEJ). To study expression of collagen IV upon aging in the DEJ and dermal fibroblasts isolated from the same patients. A model of senescent fibroblasts was developed in order to identify biological compounds that might restore the level of collagen IV. Skin fragments of women (30 to 70 years old) were collected. Localisation of collagen IV expression in the DEJ was studied by immunofluorescence. Fibroblast collagen IV expression was studied by real-time PCR, ELISA, and western blotting. Premature senescence was simulated by exposing fibroblasts to subcytotoxic H2O2 concentrations. Collagen IV decreased in the DEJ and fibroblasts relative to age. TGF-β1 treatment significantly increased collagen IV gene and protein expression in fibroblasts and restored expression in the model of senescence. Addition of TGF-β1-neutralizing antibody to fibroblast cultures decreased collagen IV expression. Taken together, the results suggest that the decrease in collagen IV in the DEJ, relative to age, could be due to a decrease in collagen IV expression by senescent dermal fibroblasts and may involve TGF-β1 signalling. PMID:27124123

  5. The accumulation mechanism of the hypoxia imaging probe “FMISO” by imaging mass spectrometry: possible involvement of low-molecular metabolites

    PubMed Central

    Masaki, Yukiko; Shimizu, Yoichi; Yoshioka, Takeshi; Tanaka, Yukari; Nishijima, Ken-ichi; Zhao, Songji; Higashino, Kenichi; Sakamoto, Shingo; Numata, Yoshito; Yamaguchi, Yoshitaka; Tamaki, Nagara; Kuge, Yuji

    2015-01-01

    18F-fluoromisonidazole (FMISO) has been widely used as a hypoxia imaging probe for diagnostic positron emission tomography (PET). FMISO is believed to accumulate in hypoxic cells via covalent binding with macromolecules after reduction of its nitro group. However, its detailed accumulation mechanism remains unknown. Therefore, we investigated the chemical forms of FMISO and their distributions in tumours using imaging mass spectrometry (IMS), which visualises spatial distribution of chemical compositions based on molecular masses in tissue sections. Our radiochemical analysis revealed that most of the radioactivity in tumours existed as low-molecular-weight compounds with unknown chemical formulas, unlike observations made with conventional views, suggesting that the radioactivity distribution primarily reflected that of these unknown substances. The IMS analysis indicated that FMISO and its reductive metabolites were nonspecifically distributed in the tumour in patterns not corresponding to the radioactivity distribution. Our IMS search found an unknown low-molecular-weight metabolite whose distribution pattern corresponded to that of both the radioactivity and the hypoxia marker pimonidazole. This metabolite was identified as the glutathione conjugate of amino-FMISO. We showed that the glutathione conjugate of amino-FMISO is involved in FMISO accumulation in hypoxic tumour tissues, in addition to the conventional mechanism of FMISO covalent binding to macromolecules. PMID:26582591

  6. Localization of a carboxylic residue possibly involved in the inhibition of vacuolar H+-pyrophosphatase by N, N'-dicyclohexylcarbodi-imide.

    PubMed Central

    Yang, S J; Jiang, S S; Kuo, S Y; Hung, S H; Tam, M F; Pan, R L

    1999-01-01

    A vacuolar H(+)-pyrophosphatase (EC 3.6.1.1) that catalyses PP(i) hydrolysis and the electrogenic translocation of protons from the cytosol to the vacuole lumen, was purified from etiolated hypocotyls of mung bean seedlings (Vigna radiata L.). Group-specific modification was used to identify a carboxylic residue involved in the inhibition of vacuolar H(+)-pyrophosphatase. Carbodi-imides, such as N,N'-dicyclohexylcarbodi-imide (DCCD) and 1-ethyl-3-(3-dimethylamino-propyl)carbodi-imide, and Woodward's reagent K caused a progressive decline in the enzymic activity of vacuolar H(+)-pyrophosphatase in a time- and concentration-dependent manner. The stoichiometry of labelling of the vacuolar H(+)-pyrophosphatase by [(14)C]DCCD determined that DCCD modifies one carboxylic residue per subunit of the enzyme. Protection studies suggest that the DCCD-reactive carboxylic residue resides at or near the substrate-binding site. Furthermore, peptide mapping analysis reveals that Asp(283), located in the putative loop V of a tentative topological model of vacuolar H(+)-pyrophosphatase on the cytosolic side, was labelled by radioactive [(14)C]DCCD. Cytosolic loop V contains both DCCD-sensitive Asp(283) and a conserved motif sequence, rendering it a candidate for the catalytic site of vacuolar H(+)-pyrophosphatase. A topological picture of the active domain of vacuolar H(+)-pyrophosphatase is tentatively proposed. PMID:10477275

  7. Purification and some properties of reovirus-like particles from leafhoppers and their possible involvement in wallaby ear disease of maize.

    PubMed

    Boccardo, G; Hatta, T; Francki, R I; Grivell, C J

    1980-01-30

    Reovirus-like particles, occurring in association with viroplasms, crystalline arrays and tubules, in the cytoplasm of Cicadulina bimaculata capable of inducing wallaby ear disease in maize, were purified from the insects by differential centrifugation, treatment with the nonionic detergent, Nonidet P-40, and sucrose density gradient centrifugation. The purified particles have a double-shelled icosahedral structure about 70 nm in diameter with external projections (A spikes) about 10 nm long located at the 12 vertices. These intact particles (IPs) are morphologically similar to those of Fiji disease virus (FDV), but are more stable. Cores were produced by enzymatic digestion of IPs with alpha-chymotrypsin. The cores are icosahedra about 57 nm in diameter with projections (B spikes) located at the 12 vertices, resembling those of FDV and cytoplasmic polyhedrosis virus. Immunization of a rabbit with purified IPs resulted in the production of antibodies specific to IPs, cores, and dsRNA. Immunoelectron microscopic investigations revealed that there is no relationship between this virus and FDV, maize rough dwarf, oat sterile dwarf, pangola stunt, and rice ragged stunt viruses, all members of the genus Fijivirus in the family Reoviridae. The nucleic acid extracted from partially purified virus was resolved into 10 segments by polyacrylamide gel electrophoresis. Reovirus-like particles or viroplasms could not be detected in thin sections of maize seedlings colonized by C. bimaculata showing wallaby ear symptoms. In the light of these data the possible etiology of wallaby ear disease is discussed. PMID:18631635

  8. Increase in telencephalic dopamine and cerebellar norepinephrine contents by hydrostatic pressure in goldfish: the possible involvement in hydrostatic pressure-related locomotion.

    PubMed

    Ikegami, Taro; Takemura, Akihiro; Choi, Eunjung; Suda, Atsushi; Tomonaga, Shozo; Badruzzaman, Muhammad; Furuse, Mitsuhiro

    2015-10-01

    Fish are faced with a wide range of hydrostatic pressure (HP) in their natural habitats. Additionally, freshwater fish are occasionally exposed to rapid changes in HP due to heavy rainfall, flood and/or dam release. Accordingly, variations in HP are one of the most important environmental cues for fish. However, little information is available on how HP information is perceived and transmitted in the central nervous system of fish. The present study examined the effect of HP (water depth of 1.3 m) on the quantities of monoamines and their metabolites in the telencephalon, optic tectum, diencephalon, cerebellum (including partial mesencephalon) and vagal lobe (including medulla oblongata) of the goldfish, Carassius auratus, using high-performance liquid chromatography. HP affected monoamine and metabolite contents in restricted brain regions, including the telencephalon, cerebellum and vagal lobe. In particular, HP significantly increased the levels of dopamine (DA) in the telencephalon at 15 min and that of norepinephrine (NE) in the cerebellum at 30 min. In addition, HP also significantly increased locomotor activity at 15 and 30 min after HP treatment. It is possible that HP indirectly induces locomotion in goldfish via telencephalic DA and cerebellar NE neuronal activity. PMID:25975379

  9. Anticancer effect of celastrol on human triple negative breast cancer: possible involvement of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways.

    PubMed

    Shrivastava, Shweta; Jeengar, Manish Kumar; Reddy, V Sudhakar; Reddy, G Bhanuprakash; Naidu, V G M

    2015-06-01

    Signaling via the phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is crucial for divergent physiological processes including transcription, translation, cell-cycle progression and apoptosis. The aim of work was to elucidate the anti-cancer effect of celastrol and the signal transduction pathways involved. Cytotoxic effect of celastrol was assessed by MTT assay on human triple negative breast cancer cells (TNBCs) and compared with that of MCF-7. Apoptosis induction was determined by AO/EtBr staining, mitochondrial membrane potential by JC-1, Annexin binding assays and modulation of apoptotic proteins and its effect on PI3K/Akt/mTOR pathway by western blotting. Celastrol induced apoptosis in TNBC cells, were supported by DNA fragmentation, caspase-3 activation and PARP cleavage. Meanwhile, celastrol triggered reactive oxygen species production with collapse of mitochondrial membrane potential, down-regulation of Bcl-2 and up-regulation of Bax expression. Celastrol effectively decreased PI3K 110α/85α enzyme activity, phosphorylation of Akt(ser473) and p70S6K1 and 4E-BP1. Although insulin treatment increased the phosphorylation of Akt(ser473), p70S6K1, 4E-BP1, celastrol abolished the insulin mediated phosphorylation. It clearly indicates that celastrol acts through PI3k/Akt/mTOR axis. We also found that celastrol inhibited the Akt/GSK3β and Akt/NFkB survival pathway. PI3K/Akt/mTOR inhibitor, PF-04691502 and mTOR inhibitor rapamycin enhanced the apoptosis-inducing effect of celastrol. These data demonstrated that celastrol induces apoptosis in TNBC cells and indicated that apoptosis might be mediated through mitochondrial dysfunction and PI3K/Akt signaling pathway. PMID:25818165

  10. Possible Involvement of Multidrug-Resistant Hepatitis B Virus sW172* Truncation Variant in the ER Stress Signaling Pathway during Hepatocarcinogenesis.

    PubMed

    Zheng, Jiajia; Jiang, Suzhen; Lu, Fengmin

    2016-07-22

    We investigated the biological effect of hepatitis B virus (HBV) rtA181T/sW172* point mutation on HBsAg secretion and the potential mechanisms involved in hepatocarcinogenesis. Full-length HBV wild type (wt) and HBV rtA181T/sW172* expression plasmids were transfected into HepG2 cell lines or were injected into C57BL/6 mice. The extracellular and intracellular expression levels of HBsAg and HBeAg proteins, in mouse serum and liver tissues were detected by ELISA. The localization of the truncated protein was characterized in vitro. The mRNA expression of endoplasmic reticulum (ER) stress gene GRP78 was determined. HBsAg levels were significantly higher in both supernatant of cells transfected with HBV wt and serum of mice injected with HBV wt, compared with that of HBV rtA181T/sW172* mutant. The reversed trend was observed in intracellular cells and intrahepatic liver cells. Wild type S protein alone could rescue this dysfunction. HBV rtA181T/sW172* truncated surface proteins showed a more aggregated cytoplasmic pattern which were also localized to the ER in comparison with HBV wt. Furthermore, GRP78 mRNA expression was increased 72 h post-transfection in HBV rtA181T/sW172* cells relative to HBV wt cells (P = 0.0154). The HBV sW172* truncation variant has a defect on HBsAg secretion which can lead to surface protein retention in the ER, where it may contribute to hepatocarcinogenesis through activating the ER stress signaling pathway. PMID:26567840

  11. Possible Involvement of Locus-Specific Methylation on Expression Regulation of LEAFY Homologous Gene (CiLFY) during Precocious Trifoliate Orange Phase Change Process

    PubMed Central

    Liu, Rong; Khan, Muhammad Rehman Gul; Hu, Chun-Gen

    2014-01-01

    DNA methylation plays an essential role in regulating plant development. Here, we described an early flowering trifoliate orange (precocious trifoliate orange, Poncirus trifoliata L. Raf) was treated with 5-azacytidine and displayed a number of phenotypic and developmental abnormalities. These observations suggested that DNA methylation might play an important role in regulating many developmental pathways including early flowering trait, and then the expression level of five key or integrated citrus flowering genes were analyzed. Our results showed that FLOWERING LOCUS T (CiFT) relative expression level was increased with the increasing concentrations of 5-AzaC. However, LEAFY (CiLFY), APETELA1 (CiAP1), TERMINAL FLOWER1 (CiTFL1), and FLOWERING LOCUS C (CiFLC) showed highest relative expression levels at 250 µΜ treatment, while decreased sharply at higher concentrations. In order to further confirm DNA methylation affects the expression of these genes, their full-length sequences were isolated by genome-walker method, and then was analyzed by using bioinformatics tools. However, only one locus-specific methylation site was observed in CiLFY sequence. Therefore, DNA methylation level of the CiLFY was investigated both at juvenile and adult stages of precocious trifoliate orange by bisulfate sequencing PCR; it has been shown that the level of DNA methylation was altered during phase change. In addition, spatial and temporal expression patterns of CiLFY promoter and a series of 5′ deletions were investigated by driving the expression of a β-glucuronidase reporter gene in Arabidopsis. Exogenous GA3 treatment on transgenic Arabidopsis revealed that GA3 might be involved in the developmental regulation of CiLFY during flowering process of precocious trifoliate orange. These results provided insights into the molecular regulation of CiLFY gene expression, which would be helpful for studying citrus flowering. PMID:24523915

  12. Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

    PubMed

    Bianchi, Enrica; Taurone, Samanta; Bardella, Lia; Signore, Alberto; Pompili, Elena; Sessa, Vincenzo; Chiappetta, Caterina; Fumagalli, Lorenzo; Di Gioia, Cira; Pastore, Francesco S; Scarpa, Susanna; Artico, Marco

    2015-10-01

    Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD). PMID:26201022

  13. Beneficial effects of EGb761 and vitamin E on haloperidol-induced vacuous chewing movements in rats: Possible involvement of S100B mechanisms.

    PubMed

    An, Hui Mei; Tan, Yun Long; Shi, Jing; Wang, Zhi Ren; Li, Jia; Wang, Yue Chan; Lv, Meng Han; Zhou, Dong Feng; Soares, Jair C; Kosten, Thoams R; Yang, Fu De; Zhang, Xiang Yang

    2016-01-15

    Tardive dyskinesia (TD) is a serious side effect induced by the long-term administration of typical antipsychotics. The pathophysiology of TD remains unclear, but experimental evidence suggests that neurodegeneration caused by free radicals may play an important role in TD development. S100B is considered a potential biomarker of structural neural and glial damage. This study investigated S100B expression in TD-related brain regions and assessed the effect of antioxidants Gingko biloba leaf extract (EGb761) and vitamin E (VE) on S100B in TD rats. A total of 32 rats were randomly divided into 4 study groups: saline control (saline), haloperidol alone group (Hal), EGb761-haloperidol (EGb-Hal), and vitamin E-haloperidol (VE-Hal). Rats were treated with haloperidol intraperitoneal injections (2mg/kg/day) each day for 5 weeks. EGb761 (50mg/kg/day) and VE (20mg/kg/day) were then administered during a 5-week withdrawal period. We performed behavioral assessments and immunohistochemically analyzed S100B expression in four TD-related brain regions. Our findings demonstrated that haloperidol administration led to a progressive increase in VCMs and in S100B expression in all four brain regions. Both EGb761 and VE reversed these changes, and there were no group differences between the EGb761 and VE groups. Our results indicated that long-term administration of haloperidol may induce VCMs and increase S100B expression in TD-related brain regions, and S100B may be a significant biomarker related to TD pathophysiology. Moreover, the antioxidant capacity of EGb761 and VE coupled with the possible neuroprotective effects of S100B may account for their success in improving the symptoms of haloperidol-induced TD. PMID:26455874

  14. Molecular genomic- and transcriptional-aspects of a teleost TRAF6 homolog: Possible involvement in immune responses of Oplegnathus fasciatus against pathogens.

    PubMed

    Umasuthan, Navaneethaiyer; Bathige, S D N K; Revathy, Kasthuri Saranya; Nam, Bo-Hye; Choi, Cheol Young; Lee, Jehee

    2015-01-01

    , these findings implicate that OfTRAF6 is not only involved in flagellin-induced signaling cascade, but also contributes to the antibacterial- and antiviral-responses. PMID:25449707

  15. In Vivo Anti-Influenza Virus Activity of Japanese Herbal (Kampo) Medicine, “Shahakusan,” and Its Possible Mode of Action

    PubMed Central

    Hokari, Rei; Nagai, Takayuki

    2012-01-01

    Background. A Kampo medicine, Shahakusan (SHS), has been prescribed in late phase of infection that causes inflammations in the lung. But effect of SHS on viral infection in respiratory tract has never been reported. Objectives. To evaluate anti-influenza virus activity of SHS and its mode of actions through immune systems. Methods. SHS (0.3 g/kg/day) was orally administered to BALB/c miceforupper (URI) or lower respiratory tract infection (LRI) of influenza virus A/PR/8/34. The virus titer of nasal lavage fluid (NLF) at 5 or 2 day postinfection (p.i.) and cytokine mRNA expressions in mandibular lymph node or lung at 5 or 4 day p.i. were evaluated for URI or LRI, respectively. The histopathological examinations of lung tissue and NK cell activity in the splenocytes were also evaluated at 4 day p.i. on LRI. Results. When SHS was administered from 7 days before to 4 days p.i. for URI, the virus titer was significantly decreased in comparison with water-treated control, and IL-4, IL-1β, and IL-10 mRNA expression was decreased, but IL-12A mRNA expression was increased. Administration of SHS from one day before to one day p.i. for LRI significantly decreased the virus titer. SHS also decreased infiltration of inflammatory cells in the bronchoalveolar spaces and damage of desquamated mucosal epithelia of bronchiole, decreased IP-10 mRNA expression, and increased NK cell activity. Conclusion. SHS has no direct effect on influenza virus infection but exerts antiviral effect in mice by its immunomodulating activity through action of NK cells and anti-inflammatory activity in the lung. PMID:23346216

  16. Somatosensory Psychophysical Losses in Inhabitants of Riverside Communities of the Tapajós River Basin, Amazon, Brazil: Exposure to Methylmercury Is Possibly Involved

    PubMed Central

    Khoury, Eliana Dirce Torres; Souza, Givago da Silva; da Costa, Carlos Araújo; de Araújo, Amélia Ayako Kamogari; de Oliveira, Cláudia Simone Baltazar; Silveira, Luiz Carlos de Lima; Pinheiro, Maria da Conceição Nascimento

    2015-01-01

    . There was a weak linear correlation between tactile sensation threshold and mercury concentration in the head hair samples. No correlation was found for the other two measurements. Mercury-exposed subjects had impaired somatosensory function compared with non-exposed control subjects. Long-term mercury exposure of riverside communities in the Tapajós river basin is a possible but not a definitely proven cause for psychophysical somatosensory losses observed in their population. Additionally, the relatively simple psychophysical measures used in this work should be followed by more rigorous measures of the same population. PMID:26658153

  17. β-D-Glucoside utilization by Mycoplasma mycoides subsp. mycoides SC: possible involvement in the control of cytotoxicity towards bovine lung cells

    PubMed Central

    Vilei, Edy M; Correia, Ivone; Ferronha, M Helena; Bischof, Daniela F; Frey, Joachim

    2007-01-01

    Background Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subsp. mycoides small-colony type (SC) is among the most serious threats for livestock producers in Africa. Glycerol metabolism-associated H2O2 production seems to play a crucial role in virulence of this mycoplasma. A wide number of attenuated strains of M. mycoides subsp. mycoides SC are currently used in Africa as live vaccines. Glycerol metabolism is not affected in these vaccine strains and therefore it does not seem to be the determinant of their attenuation. A non-synonymous single nucleotide polymorphism (SNP) in the bgl gene coding for the 6-phospho-β-glucosidase (Bgl) has been described recently. The SNP differentiates virulent African strains isolated from outbreaks with severe CBPP, which express the Bgl isoform Val204, from strains to be considered less virulent isolated from CBPP outbreaks with low mortality and vaccine strains, which express the Bgl isoform Ala204. Results Strains of M. mycoides subsp. mycoides SC considered virulent and possessing the Bgl isoform Val204, but not strains with the Bgl isoform Ala204, do trigger elevated levels of damage to embryonic bovine lung (EBL) cells upon incubation with the disaccharides (i.e., β-D-glucosides) sucrose and lactose. However, strains expressing the Bgl isoform Val204 show a lower hydrolysing activity on the chromogenic substrate p-nitrophenyl-β-D-glucopyranoside (pNPbG) when compared to strains that possess the Bgl isoform Ala204. Defective activity of Bgl in M. mycoides subsp. mycoides SC does not lead to H2O2 production. Rather, the viability during addition of β-D-glucosides in medium-free buffers is higher for strains harbouring the Bgl isoform Val204 than for those with the isoform Ala204. Conclusion Our results indicate that the studied SNP in the bgl gene is one possible cause of the difference in bacterial virulence among strains of M. mycoides subsp. mycoides SC. Bgl does not act as a direct virulence

  18. Ethanol Extract of Peanut Sprout Lowers Blood Triglyceride Levels, Possibly Through a Pathway Involving SREBP-1c in Rats Fed a High-Fat Diet.

    PubMed

    Ha, Ae Wha; Kang, Nam E; Kim, Woo Kyoung

    2015-08-01

    The hypothesis of this study was that peanut sprout extracts (PSE) could reduce fat accumulation through activating the transcription of SREBP-1c genes. Sprague-Dawley (SD) were randomly assigned into two groups and fed the following diet for 4 weeks; 10 normal fat (NF, 7 g of fat/100 g diet) and 30 high fat (HF, 20 g of fat/100 g diet). After 4 weeks, the HF group was divided into three groups; HF, HF with 15 mg of PSE/kg diet (HF+low PSE, 0.025% resveratrol), and HF with 30 mg of PSE/kg diet (HF+high PSE, 0.05% resveratrol) and fed for an additional 5 weeks. The HF+high PSE group had significantly lower weight gain than the HF group. Plasma triglyceride (TG) level and the hepatic total lipid level were significantly lower in the HF+high PSE group compared to the HF group. Fecal excretions of total lipids, cholesterol, and TG in the HF+high PSE group tended to be higher than in the HF group, but these differences were not significant. The mRNA expressions of fatty acid synthase, glucose-6-phosphate dehydrogenase, and sterol regulatory element binding protein-c (SREBP-1c) were significantly lower in the HF+high PSE group than in the HF group. The mRNA expressions of hydroxy-3-methylglutaryl coenzyme A reductase and acyl-CoA cholesterol acyltransferase were significantly lower in the HF+high PSE groups compared to the HF group. The mRNA expression of cholesterol 7α-hydroxylase1 was significantly higher than the HF group in both the HF+low PSE and HF+high PSE groups, with much greater increase observed in the HF+high PSE group. In conclusion, consumption of PSE was effective for improving blood lipid levels, possibly by suppressing the expression of SREBP-1c, in rats fed a high-fat diet. PMID:25946626

  19. Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/β-Catenin Pathway.

    PubMed

    Ge, Jin-Fang; Xu, Ya-Yun; Qin, Gan; Cheng, Jiang-Qun; Chen, Fei-Hu

    2016-01-01

    Metabolic disease subclinical hypothyroidism (SCH) is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES) in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 μg/kg for 16 days. The rats' plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA) activity were evaluated. The protein expression levels of the Wnt/β-catenin in the hippocampus were detected by western blot. The results showed that RES treatment downregulated the elevated plasma thyroid-stimulating hormone concentration and the hypothalamic mRNA expression of thyrotropin-releasing hormone in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the open-field test, increased sucrose preference in the sucrose preference test, and decreased immobility in the forced swimming test compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels, and the hypothalamic corticotrophin-releasing hormone mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment upregulated the relative ratio of phosphorylated-GSK3β (p-GSK3β)/GSK3β and protein levels of p-GSK3β, cyclin D1, and c-myc, while downregulating the relative ratio of phosphorylated-β-catenin (p-β-catenin)/β-catenin and expression of GSK3β in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by downregulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt

  20. Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/β-Catenin Pathway

    PubMed Central

    Ge, Jin-Fang; Xu, Ya-Yun; Qin, Gan; Cheng, Jiang-Qun; Chen, Fei-Hu

    2016-01-01

    Metabolic disease subclinical hypothyroidism (SCH) is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES) in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 μg/kg for 16 days. The rats’ plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic–pituitary–adrenal (HPA) activity were evaluated. The protein expression levels of the Wnt/β-catenin in the hippocampus were detected by western blot. The results showed that RES treatment downregulated the elevated plasma thyroid-stimulating hormone concentration and the hypothalamic mRNA expression of thyrotropin-releasing hormone in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the open-field test, increased sucrose preference in the sucrose preference test, and decreased immobility in the forced swimming test compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels, and the hypothalamic corticotrophin-releasing hormone mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment upregulated the relative ratio of phosphorylated-GSK3β (p-GSK3β)/GSK3β and protein levels of p-GSK3β, cyclin D1, and c-myc, while downregulating the relative ratio of phosphorylated-β-catenin (p-β-catenin)/β-catenin and expression of GSK3β in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by downregulating hyperactivity of the HPA axis and regulating both the HPT axis and the

  1. Beetroot juice reduces infarct size and improves cardiac function following ischemia-reperfusion injury: Possible involvement of endogenous H2S.

    PubMed

    Salloum, Fadi N; Sturz, Gregory R; Yin, Chang; Rehman, Shabina; Hoke, Nicholas N; Kukreja, Rakesh C; Xi, Lei

    2015-05-01

    Ingestion of high dietary nitrate in the form of beetroot juice (BRJ) has been shown to exert antihypertensive effects in humans through increasing cyclic guanosine monophosphate (cGMP) levels. Since enhanced cGMP protects against myocardial ischemia-reperfusion (I/R) injury through upregulation of hydrogen sulfide (H2S), we tested the hypothesis that BRJ protects against I/R injury via H2S. Adult male CD-1 mice received either regular drinking water or those dissolved with BRJ powder (10 g/L, containing ∼ 0.7 mM nitrate). Seven days later, the hearts were explanted for molecular analyses. Subsets of mice were subjected to I/R injury by occlusion of the left coronary artery for 30 min and reperfusion for 24 h. A specific inhibitor of H2S producing enzyme--cystathionine-γ-lyase (CSE), DL-propargylglycine (PAG, 50 mg/kg) was given i.p. 30 min before ischemia. Myocardial infarct size was significantly reduced in BRJ-fed mice (15.8 ± 3.2%) versus controls (46.5 ± 3.5%, mean ± standard error [SE], n = 6/group, P < .05). PAG completely blocked the infarct-limiting effect of BRJ. Moreover, BRJ significantly preserved ventricular function following I/R. Myocardial levels of H2S and its putative protein target--vascular endothelial growth factor receptor 2 (VEGFR2) were significantly increased by BRJ intake, whereas CSE mRNA and protein content did not change. Interestingly, the BRJ-induced cardioprotection was not associated with elevated blood nitrate-nitrite levels following I/R nor induction of cardiac peroxiredoxin 5, a mitochondrial antioxidant enzyme previously linked to nitrate-induced cardioprotection. We conclude that BRJ ingestion protects against post-I/R myocardial infarction and ventricular dysfunction possibly through CSE-mediated endogenous H2S generation. BRJ could be a promising natural and inexpensive nutraceutical supplement to reduce cardiac I/R injury in patients. PMID:25361774

  2. Connexin43 gap junctions in normal, regenerating, and cultured mouse bone marrow and in human leukemias: their possible involvement in blood formation.

    PubMed Central

    Krenacs, T.; Rosendaal, M.

    1998-01-01

    their membrane replicas. In normocellular human bone marrow, gap junctions were as rare as in adult mouse and similarly distributed, except that they were also on adipocytic membranes. In a few leukemic samples, characterized by an increased stromal/hematopoietic cell ratio, there were two- to fourfold more Cx43 (2.8 x 10(5) to 3.9 x 10(5)/mm3) than in the normal (1.0 x 10(5) to 1.2 x 10(5)/mm3). The cases included a hypoplastic acute lymphoblastic leukemia, an acute myeloid leukemia (French-American-British classification M4-5), a case of myelodysplastic syndrome with elevated number of megakaryocytes, and a CD34+ acute hemoblastosis, probably acute myeloid leukemia (French-American-British classification M7). Taken together, our results indicate that direct cell-cell communication may be involved in hematopoiesis, ie, in developmentally active epiphyseal bone marrow and when there is a demand for progenitors in regeneration. However, gap junctions may not play as important a role in resting adult hematopoiesis and in leukemias. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 10 PMID:9546360

  3. An Examination of Attitudes and Actions of Regular Classroom and Gifted Teachers toward Differentiating for Gifted Learners Involved in a Pullout Gifted Program

    ERIC Educational Resources Information Center

    Logan, Melissa N.

    2011-01-01

    Bridging the gap in student performance has changed the teaching practice in classrooms across America. Educators have the responsibility to teach all learners. There is a need for instruction to be tailored to boost the higher-level achievers and balance the gaps. This study examined the attitudes and actions of regular and gifted teachers…

  4. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure

    PubMed Central

    Christophersen, Olav Albert

    2012-01-01

    tissues, especially in the intestines, and (4) by functioning as an antifibrogenic agent. A detailed discussion is given of possible mechanisms involved both in the antioxidant effects of taurine, in its anti-inflammatory effects and in its role as a growth factor for leukocytes and nerve cells, which might be closely related to its role as an osmolyte important for cellular volume regulation because of the close connection between cell volume regulation and the regulation of protein synthesis as well as cellular protein degradation. While taurine supplementation alone would be expected to exert a therapeutic effect far better than negligible in patients that have been exposed to high doses of ionizing radiation, it may on theoretical grounds be expected that much better results may be obtained by using taurine as part of a multifactorial treatment strategy, where it may interact synergistically with several other nutrients, hormones or other drugs for optimizing antioxidant protection and minimizing harmful posttraumatic inflammatory reactions, while using other nutrients to optimize DNA and tissue repair processes, and using a combination of good diet, immunostimulatory hormones and perhaps other nontoxic immunostimulants (such as beta-glucans) for optimizing the recovery of antiviral and antibacterial immune functions. Similar multifactorial treatment strategies may presumably be helpful in several other disease situations (including severe infectious diseases and severe asthma) as well as for treatment of acute intoxications or acute injuries (both mechanical ones and severe burns) where severely enhanced oxidative and/or nitrative stress and/or too much secretion of vasodilatory neuropeptides from C-fibres are important parts of the pathogenetic mechanisms that may lead to the death of the patient. Some case histories (with discussion of some of those mechanisms that may have been responsible for the observed therapeutic outcome) are given for illustration of the

  5. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

    PubMed

    Christophersen, Olav Albert

    2012-01-01

    tissues, especially in the intestines, and (4) by functioning as an antifibrogenic agent. A detailed discussion is given of possible mechanisms involved both in the antioxidant effects of taurine, in its anti-inflammatory effects and in its role as a growth factor for leukocytes and nerve cells, which might be closely related to its role as an osmolyte important for cellular volume regulation because of the close connection between cell volume regulation and the regulation of protein synthesis as well as cellular protein degradation. While taurine supplementation alone would be expected to exert a therapeutic effect far better than negligible in patients that have been exposed to high doses of ionizing radiation, it may on theoretical grounds be expected that much better results may be obtained by using taurine as part of a multifactorial treatment strategy, where it may interact synergistically with several other nutrients, hormones or other drugs for optimizing antioxidant protection and minimizing harmful posttraumatic inflammatory reactions, while using other nutrients to optimize DNA and tissue repair processes, and using a combination of good diet, immunostimulatory hormones and perhaps other nontoxic immunostimulants (such as beta-glucans) for optimizing the recovery of antiviral and antibacterial immune functions. Similar multifactorial treatment strategies may presumably be helpful in several other disease situations (including severe infectious diseases and severe asthma) as well as for treatment of acute intoxications or acute injuries (both mechanical ones and severe burns) where severely enhanced oxidative and/or nitrative stress and/or too much secretion of vasodilatory neuropeptides from C-fibres are important parts of the pathogenetic mechanisms that may lead to the death of the patient. Some case histories (with discussion of some of those mechanisms that may have been responsible for the observed therapeutic outcome) are given for illustration of the

  6. Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

    2011-02-01

    Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

  7. Effects and possible mechanisms of action of acacetin on the behavior and eye morphology of Drosophila models of Alzheimer’s disease

    PubMed Central

    Wang, Xue; Perumalsamy, Haribalan; Kwon, Hyung Wook; Na, Young-Eun; Ahn, Young-Joon

    2015-01-01

    The human β-amyloid (Aβ) cleaving enzyme (BACE-1) is a target for Alzheimer’s disease (AD) treatments. This study was conducted to determine if acacetin extracted from the whole Agastache rugosa plant had anti-BACE-1 and behavioral activities in Drosophila melanogaster AD models and to determine acacetin’s mechanism of action. Acacetin (100, 300, and 500 μM) rescued amyloid precursor protein (APP)/BACE1-expressing flies and kept them from developing both eye morphology (dark deposits, ommatidial collapse and fusion, and the absence of ommatidial bristles) and behavioral (motor abnormalities) defects. The reverse transcription polymerase chain reaction analysis revealed that acacetin reduced both the human APP and BACE-1 mRNA levels in the transgenic flies, suggesting that it plays an important role in the transcriptional regulation of human BACE-1 and APP. Western blot analysis revealed that acacetin reduced Aβ production by interfering with BACE-1 activity and APP synthesis, resulting in a decrease in the levels of the APP carboxy-terminal fragments and the APP intracellular domain. Therefore, the protective effect of acacetin on Aβ production is mediated by transcriptional regulation of BACE-1 and APP, resulting in decreased APP protein expression and BACE-1 activity. Acacetin also inhibited APP synthesis, resulting in a decrease in the number of amyloid plaques. PMID:26530776

  8. Hypoglycaemic activity of culinary Pleurotus ostreatus and P. cystidiosus mushrooms in healthy volunteers and type 2 diabetic patients on diet control and the possible mechanisms of action.

    PubMed

    Jayasuriya, W J A Banukie N; Wanigatunge, Chandanie A; Fernando, Gita H; Abeytunga, D Thusitha U; Suresh, T Sugandhika

    2015-02-01

    This study determined the oral hypoglycaemic effect of suspensions of freeze dried and powdered (SFDP) Pleurotus ostreatus (P.o) and Pleurotus cystidiosus (P.c), using healthy human volunteers and Type 2 diabetic patients on diet control at a dose of 50 mg/kg/body weight, followed by a glucose load. The possible hypoglycaemic mechanisms were evaluated using rats, by examining intestinal glucose absorption and serum levels of insulin, glucokinase (GK) and glycogen synthase kinase (GSK). The P.o and P.c showed a significant reduction (P < 0.05) in fasting and postprandial serum glucose levels of healthy volunteers and reduced the postprandial serum glucose levels and increased the serum insulin levels (P < 0.05) of Type 2 diabetic patients. The P.o and P.c increased the intestinal absorption of glucose but simultaneously reduced the serum glucose levels (P < 0.05) in rats. Both mushrooms reduced the serum GSK and promoted insulin secretion while P.c increased serum GK (P < 0.05). The hypoglycaemic activity of P.o and P.c makes mushrooms beneficial functional foods in diabetes mellitus. The mechanism of hypoglycaemic activity of P.o and P.c is possibly by increasing GK activity and promoting insulin secretion and thereby increasing the utilization of glucose by peripheral tissues, inhibiting GSK and promoting glycogen synthesis. PMID:25382404

  9. Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: mechanism of action and possible interactions with cholinergic system.

    PubMed

    Kruk-Slomka, Marta; Michalak, Agnieszka; Biala, Grazyna

    2015-05-01

    The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice. Our results revealed that acute injection of oleamide (10 and 20 mg/kg), a CB1 receptor agonist, caused antidepressant-like effect in the FST, while AM 251 (0.25-3 mg/kg), a CB1 receptor antagonist, did not provoke any effect in this test. Moreover, acute administration of both CB2 receptor agonist, JWH 133 (0.5 and 1 mg/kg) and CB2 receptor antagonist, AM 630 (0.5 mg/kg), exhibited antidepressant action. Antidepressant effects of oleamide and JWH 133 were attenuated by acute injection of both non-effective dose of AM 251, as well as AM 630. Among the all CB compounds used, only the combination of non-effective dose of oleamide (2.5 mg/kg) with non-effective dose of nicotine (0.5 mg/kg) caused an antidepressant effect. However, none of the CB receptor ligands, had influence on the antidepressant effects provoked by nicotine (0.2 mg/kg) injection. In turn, the combination of non-effective dose of oleamide (2.5 mg/kg); JWH (2 mg/kg) or AM 630 (2 mg/kg), but not of AM 251 (0.25 mg/kg), with non-effective dose of scopolamine (0.1 mg/kg), exhibited antidepressant properties. Indeed, all of the CB compounds used, intensified the antidepressant-like effects induced by an acute injection of scopolamine (0.3 mg/kg). Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses. PMID:25660201

  10. Molecular mechanism of action of triazolobenzodiazepinone agonists of the type 1 cholecystokinin receptor. Possible cooperativity across the receptor homo-dimeric complex

    PubMed Central

    Desai, Aditya J.; Lam, Polo C.H.; Orry, Andrew; Abagyan, Ruben; Christopoulos, Arthur; Sexton, Patrick M.; Miller, Laurence J.

    2016-01-01

    The type 1 cholecystokinin receptor (CCK1R) has multiple physiologic roles relating to nutrient homeostasis, including mediation of post-cibal satiety. This effect has been central in efforts to develop agonists of this receptor as part of a program to manage and/or prevent obesity. While a number of small molecule CCK1R agonists have been developed, none has yet been approved for clinical use, based on inadequate efficacy, side effects, or the potential for toxicity. Understanding the molecular details of docking and mechanism of action of these ligands can be helpful in the rational refinement and enhancement of small molecule drug candidates. In the current work, we have defined the mechanism of binding and activity of two triazolobenzodiazepinones, CE-326597 and PF-04756956, which are reported to be full agonist ligands. To achieve this, we utilized receptor binding with a series of allosteric and orthosteric radioligands at structurally-related CCK1R and CCK2R, as well as chimeric CCK1R/CCK2R constructs exchanging residues in the allosteric pocket, and assessment of biological activity. These triazolobenzodiazepinones docked within the intramembranous small molecule allosteric ligand pocket, with higher affinity binding to CCK2R than CCK1R, yet with biological activity exclusive to or greatly enhanced at CCK1R. These ligands exhibited cooperativity with benzodiazepine binding across the CCK1R homodimeric complex, resulting in their ability to inhibit only a fraction of the saturable binding of a benzodiazepine radioligand, unlike other small molecule antagonists and agonists of this receptor. This may contribute to the understanding of the unique short duration and reversible gallbladder contraction observed in vivo upon administration of these drugs. PMID:26654202

  11. The neuroprotective effects and possible mechanism of action of a methanol extract from Asparagus cochinchinensis: In vitro and in vivo studies.

    PubMed

    Jalsrai, A; Numakawa, T; Kunugi, H; Dieterich, D C; Becker, A

    2016-05-13

    Extracts of Asparagus cochinchinensis (AC) have antitumor, anti-inflammatory, and immunostimulant effects. The neurobiological mechanisms underlying the effects of AC have not been sufficiently explored. Thus we performed in vivo and in vitro experiments to further characterize potential therapeutic effects and to clarify the underlying mechanisms. In the tail suspension test immobility time was significantly reduced after administration of AC which suggests antidepressant-like activity without effect on body core temperature. Moreover, in animals pretreated with AC infarct size after occlusion of the middle cerebral artery was reduced. In vitro experiments confirmed neuroprotective effects. Total saponin obtained from AC significantly inhibited H2O2-induced cell death in cultured cortical neurons. The survival-promoting effect by AC saponins was partially blocked by inhibitors for extracellular signal-regulated kinase (ErK) and phosphoinositide 3-kinase Akt (PI3K/Akt) cascades, both of which are known as survival-promoting signaling molecules. Furthermore, phosphorylation of Scr homology-2 (SH2) domain-containing phosphatase 2 (Shp-2) was induced by AC, and the protective effect of AC was abolished by NSC87877, an inhibitor for Shp-2, suggesting an involvement of Shp-2 mediated intracellular signaling in AC saponins. Moreover, AC-induced activation of pShp-2 and ErK1/2 were blocked by NSC87877 indicating that activation of these signaling pathways was mediated by the Shp-2 signaling pathway. These effects appear to be associated with activation of the Shp-2, ErK1/2 and Akt signaling pathways. Our results suggest that AC has antidepressant-like and neuroprotective (reducing infarct size) effects and that activation of pShp-2 and pErK1/2 pathways may be involved in the effects. PMID:26947129

  12. Opto-acoustic diagnostics of the thermal action of high-intensity focused ultrasound on biological tissues: the possibility of its applications and model experiments

    SciTech Connect

    Khokhlova, Tanya D; Pelivanov, Ivan M; Solomatin, Vladimir S; Karabutov, Aleksander A; Sapozhnikov, Oleg A

    2006-12-31

    The possibility of using the opto-acoustic (OA) method for monitoring high-intensity ultrasonic therapy is studied. The optical properties of raw and boiled liver samples used as the undamaged model tissue and tissue destroyed by ultrasound, respectively, are measured. Experiments are performed with samples consisting of several alternating layers of raw and boiled liver of different thickness. The position and transverse size of the thermal lesion were determined from the temporal shape of the OA signals. The results of measurements are compared with the real size and position of the thermal lesion determined from the subsequent cuts of the sample. It is shown that the OA method permits the diagnostics of variations in biological tissues upon ultrasonic therapy. (special issue devoted to multiple radiation scattering in random media)

  13. Effects of clove oil-phospholipid mixtures on rheology of gum tragacanth - possible application for surfactant action on mucus gel simulants.

    PubMed

    Banerjee, R; Puniyani, R R

    2000-01-01

    The present study evaluates the effectiveness of specialised biomaterials consisting of clove oil- phospholipid mixtures as possible substitute surfactants in diseases of altered mucus viscosity by studying their effect on the viscosity of mucus gel simulants in vitro. Test surfactants consisting of phospholipid-clove oil mixtures in the ratio of 1 part of oil to 9 parts of phospholipid were prepared. The phospholipids used were dipalmitoyl phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) and binary mixtures of PC: PE and PC: PG in the ratio of 2 parts of PC to 3 parts of PE or PG. The effects of the phospholipid-clove oil mixtures on the viscosity of mucus gel simulant (MGS: a polymeric gel consisting predominantly of gum tragacanth and simulating respiratory mucus), was studied by application of steady shear rates ranging from 0.512 to 51.2/s in a concentric cylinder viscometer at 37 degrees C. The change in MGS viscosity, after incubation with surfactants, was found to have a non-Newtonian character and to follow the power law model with R2 values >0.8. The addition of clove oil-phospholipid mixtures caused a decrease in the MGS viscosity when compared with the effect of the phospholipid alone at low shear rates in case of PC, PG and PCPG. The combination of PC : PG with clove oil caused ratios of change in MGS viscosity < 1 i.e., caused a decrease in the MGS viscosity. PC: PG with clove oil was capable of lowering MGS viscosity and should be further researched as possible therapies for diseases of altered mucus rheology. PMID:11202146

  14. Involvement of Hormone- and ROS-Signaling Pathways in the Beneficial Action of Humic Substances on Plants Growing under Normal and Stressing Conditions

    PubMed Central

    García, Andrés Calderín; Olaetxea, Maite; Santos, Leandro Azevedo; Mora, Verónica; Baigorri, Roberto; Fuentes, Marta; Zamarreño, Angel Maria; Berbara, Ricardo Luis Louro; Garcia-Mina, José María

    2016-01-01

    The importance of soil humus in soil fertility has been well established many years ago. However, the knowledge about the whole mechanisms by which humic molecules in the rhizosphere improve plant growth remains partial and rather fragmentary. In this review we discuss the relationships between two main signaling pathway families that are affected by humic substances within the plant: one directly related to hormonal action and the other related to reactive oxygen species (ROS). In this sense, our aims are to try the integration of all these events in a more comprehensive model and underline some points in the model that remain unclear and deserve further research. PMID:27366744

  15. Involvement of Hormone- and ROS-Signaling Pathways in the Beneficial Action of Humic Substances on Plants Growing under Normal and Stressing Conditions.

    PubMed

    García, Andrés Calderín; Olaetxea, Maite; Santos, Leandro Azevedo; Mora, Verónica; Baigorri, Roberto; Fuentes, Marta; Zamarreño, Angel Maria; Berbara, Ricardo Luis Louro; Garcia-Mina, José María

    2016-01-01

    The importance of soil humus in soil fertility has been well established many years ago. However, the knowledge about the whole mechanisms by which humic molecules in the rhizosphere improve plant growth remains partial and rather fragmentary. In this review we discuss the relationships between two main signaling pathway families that are affected by humic substances within the plant: one directly related to hormonal action and the other related to reactive oxygen species (ROS). In this sense, our aims are to try the integration of all these events in a more comprehensive model and underline some points in the model that remain unclear and deserve further research. PMID:27366744

  16. Involvement of the Receptor for Formylated Peptides in the in Vivo Anti-Migratory Actions of Annexin 1 and its Mimetics

    PubMed Central

    Perretti, Mauro; Getting, Stephen J.; Solito, Egle; Murphy, Philip M.; Gao, Ji-Liang

    2001-01-01

    An innovative avenue for anti-inflammatory therapy is inhibition of neutrophil extravasation by potentiating the action of endogenous anti-inflammatory mediators. The glucocorticoid-inducible protein annexin 1 and derived peptides are effective in inhibiting neutrophil extravasation. Here we tested the hypothesis that an interaction with the receptor for formylated peptide (FPR), so far reported only in vitro, could be the mechanism for this in vivo action. In a model of mouse peritonitis, FPR antagonists abrogated the anti-migratory effects of peptides Ac2-26 and Ac2-12, with a partial reduction in annexin 1 effects. A similar result was obtained in FPR (knock-out) KO mice. Binding of annexin 1 to circulating leukocytes was reduced (>50%) in FPR KO mice. In vitro, annexin binding to peritoneal macrophages was also markedly reduced in FPR KO mice. Finally, evidence of direct annexin 1 binding to murine FPR was obtained with HEK-293 cells transfected with the receptor. Overall, these results indicate a functional role for FPR in the anti-migratory effect of annexin 1 and derived peptides. PMID:11395373

  17. The Employer-Supported Parental Involvement in Education Program (ES/PIE): An Educator's Action Guide to ES/PIE Program Implementation.

    ERIC Educational Resources Information Center

    Espinoza, Renato; Ramos-Cancel, Maria L.

    Described are characteristics of the Employer-Supported Parental Involvement in Education program (ES/PIE), designed to foster collaboration between education agencies and employers. An overview of the program details basic assumptions, core activities, and the roles of school districts and employers. Subsequent content provides a guide to program…

  18. The Effect of (-)-Epigallocatechin 3-O - Gallate In Vitro and In Vivo in Leishmania braziliensis: Involvement of Reactive Oxygen Species as a Mechanism of Action

    PubMed Central

    Inacio, Job D. F.; Gervazoni, Luiza; Canto-Cavalheiro, Marilene M.; Almeida-Amaral, Elmo E.

    2014-01-01

    Background Leishmaniasis is a parasitic disease associated with extensive mortality and morbidity. The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. Natural compounds have been used as novel treatments for parasitic diseases. In this paper, we evaluated the effect of (-)-epigallocatechin 3-O-gallate (EGCG) on Leishmania braziliensis in vitro and in vivo and described the mechanism of EGCG action against L. braziliensis promastigotes and intracellular amastigotes. Methodology/Principal Finding In vitro activity and reactive oxygen species (ROS) measurements were determined during the promastigote and intracellular amastigote life stages. The effect of EGCG on mitochondrial membrane potential (ΔΨm) was assayed using JC-1, and intracellular ATP concentrations were measured using a luciferin-luciferase system. The in vivo experiments were performed in infected BALB/c mice orally treated with EGCG. EGCG reduced promastigote viability and the infection index in a time- and dose-dependent manner, with IC50 values of 278.8 µM and 3.4 µM, respectively, at 72 h and a selectivity index of 149.5. In addition, EGCG induced ROS production in the promastigote and intracellular amastigote, and the effects were reversed by polyethylene glycol (PEG)-catalase. Additionally, EGCG reduced ΔΨm, thereby decreasing intracellular ATP concentrations in promastigotes. Furthermore, EGCG treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study demonstrates the leishmanicidal effects of EGCG against the two forms of L. braziliensis, the promastigote and amastigote. In addition, EGCG promotes ROS production as a part of its mechanism of action, resulting in decreased ΔΨm and reduced intracellular ATP concentrations. These actions ultimately

  19. Application of the U.S. EPA mode of action Framework for purposes of guiding future research: a case study involving the oral carcinogenicity of hexavalent chromium.

    PubMed

    Thompson, Chad M; Haws, Laurie C; Harris, Mark A; Gatto, Nicole M; Proctor, Deborah M

    2011-01-01

    Mode of action (MOA) analysis provides a systematic description of key events leading to adverse health effects in animal bioassays for the purpose of informing human health risk assessment. Uncertainties and data gaps identified in the MOA analysis may also be used to guide future research to improve understanding of the MOAs underlying a specific toxic response and foster development of toxicokinetic and toxicodynamic models. An MOA analysis, consistent with approaches outlined in the MOA Framework as described in the Guidelines for Carcinogen Risk Assessment, was conducted to evaluate small intestinal tumors observed in mice chronically exposed to relatively high concentrations of hexavalent chromium (Cr(VI)) in drinking water. Based on review of the literature, key events in the MOA are hypothesized to include saturation of the reductive capacity of the upper gastrointestinal tract, absorption of Cr(VI) into the intestinal epithelium, oxidative stress and inflammation, cell proliferation, direct and/or indirect DNA modification, and mutagenesis. Although available data generally support the plausibility of these key events, several unresolved questions and data gaps were identified, highlighting the need for obtaining critical toxicokinetic and toxicodynamic data in the target tissue and in the low-dose range. Experimental assays that can address these data gaps are discussed along with strategies for comparisons between responsive and nonresponsive tissues and species. This analysis provides a practical application of MOA Framework guidance and is instructive for the design of studies to improve upon the information available for quantitative risk assessment. PMID:20947717

  20. From plans to actions in patient and public involvement: qualitative study of documented plans and the accounts of researchers and patients sampled from a cohort of clinical trials

    PubMed Central

    Buck, Deborah; Gamble, Carrol; Dudley, Louise; Preston, Jennifer; Hanley, Bec; Williamson, Paula R; Young, Bridget

    2014-01-01

    Patient and public involvement (PPI) in research is increasingly required, although evidence to inform its implementation is limited. Objective Inform the evidence base by describing how plans for PPI were implemented within clinical trials and identifying the challenges and lessons learnt by research teams. Methods We compared PPI plans extracted from clinical trial grant applications (funded by the National Institute for Health Research Health Technology Assessment Programme between 2006 and 2010) with researchers’ and PPI contributors’ interview accounts of PPI implementation. Analysis of PPI plans and transcribed qualitative interviews drew on the Framework technique. Results Of 28 trials, 25 documented plans for PPI in funding applications and half described implementing PPI before applying for funding. Plans varied from minimal to extensive, although almost all anticipated multiple modes of PPI. Interview accounts indicated that PPI plans had been fully implemented in 20/25 trials and even expanded in some. Nevertheless, some researchers described PPI within their trials as tokenistic. Researchers and contributors noted that late or minimal PPI engagement diminished its value. Both groups perceived uncertainty about roles in relation to PPI, and noted contributors’ lack of confidence and difficulties attending meetings. PPI contributors experienced problems in interacting with researchers and understanding technical language. Researchers reported difficulties finding ‘the right’ PPI contributors, and advised caution when involving investigators’ current patients. Conclusions Engaging PPI contributors early and ensuring ongoing clarity about their activities, roles and goals, is crucial to PPI's success. Funders, reviewers and regulators should recognise the value of preapplication PPI and allocate further resources to it. They should also consider whether PPI plans in grant applications match a trial's distinct needs. Monitoring and reporting PPI

  1. Action in Development

    ERIC Educational Resources Information Center

    von Hofsten, Claes

    2007-01-01

    It is argued that cognitive development has to be understood in the functional perspective provided by actions. Actions reflect all aspects of cognitive development including the motives of the child, the problems to be solved, and the constraints and possibilities of the child's body and sensorimotor system. Actions are directed into the future…

  2. Regional involvement of an endothelium-derived contractile factor in the vasoactive actions of neuropeptide Y in bovine isolated retinal arteries.

    PubMed Central

    Prieto, D.; Simonsen, U.; Nyborg, N. C.

    1995-01-01

    1. In vitro experiments in a microvascular myograph were designed in order to investigate the effects of human neuropeptide Y (NPY), its receptor subtype and the mechanisms underlying NPY actions in bovine isolated retinal proximal (PRA) and distal (DRA) arteries. 2. A single concentration of NPY (10 nM) induced a prompt and reproducible contraction which reached a plateau within 1-4 min, after which the response returned to baseline over the next 2-10 min. Cumulative addition of NPY induced concentration-dependent contractions of bovine retinal arteries, with an EC50[M] of 1.7 nM and a maximal response equal to 54 +/- 8% of Emax (absolute maximal contractile levels of vessels) and not different from that obtained by a single addition of the peptide. There were no significant differences in either sensitivity or maximal response to NPY between PRA and DRA. 3. Porcine NPY and the selective Y1-receptor agonist, [Pro34]NPY, also induced concentration-dependent contractions of the retinal arteries with a potency and maximal response not significantly different from those of human NPY; in contrast, the selective Y2-receptor agonist, NPY(13-36), caused only a 5% contraction at the highest concentration used. 4. Removal of extracellular Ca2+ or pretreatment with the 1,4-dihydropyridine Ca(2+)-channel blocker, nifedipine (1 microM), reduced the contractile response of 10 nM NPY to 18.4 +/- 3.3% (n = 6) and 18.6 +/- 3.9% (n = 6); respectively, of the controls. 5. Mechanical removal of the endothelium depressed the maximal contraction elicited by NPY in PRA but did not affect either sensitivity or maximal response to the peptide in DRA. In endothelium-intact arteries, blockade of the cyclo-oxygenase pathway with 3 microM indomethacin increased resting tension in both PRA and DRA and significantly inhibited sensitivity and maximal contraction to NPY of PRA and DRA, respectively. The thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist, SQ30741, reduced both

  3. Involvement of protein kinase C and intracellular Ca2+ in goldfish brain somatostatin-28 inhibitory action on growth hormone release in goldfish.

    PubMed

    Yu, Y; Chang, J P

    2010-08-01

    Goldfish brain somatostatin-28 (gbSS-28) is present in brain and pituitary tissues of goldfish. We assessed whether gbSS-28 targets Ca(2+) and/or protein kinase C (PKC)-dependent signaling cascades in inhibiting growth hormone (GH) release. gbSS-28 decreased basal GH release from primary cultures of dispersed goldfish pituitary cells and intracellular free calcium levels ([Ca(2+)](i)) in goldfish somatotropes. gbSS-28 partially reduced [Ca(2+)](i) and GH responses induced by two endogeneous gonadotropin-releasing hormones (GnRHs), salmon (s)GnRH and chicken (c)GnRH-II. Furthermore, gbSS-28 reduced GH increases and abolished [Ca(2+)](i) elevations elicited by two PKC activators, tetradecanoyl 4beta-phorbol-13-acetate and dioctanyl glycerol. The PKC inhibitors Gö6976 and Bis II abolished [Ca(2+)](i) responses to PKC activators, but only attenuated GnRH-induced increases in [Ca(2+)](i) and did not alter basal [Ca(2+)](i). In cells pretreated with Bis II, gbSS-28 further reduced basal [Ca(2+)](i). Our results suggest that gbSS-28 inhibits GnRH-induced GH release in part by attenuating PKC-mediated GnRH [Ca(2+)](i) signals. gbSS-28 reduces basal GH release also via reduction in [Ca(2+)](i) but PKC is not involved in this regard. PMID:20403359

  4. Hormonal regulation of gluconeogenesis in cereal aleurone is strongly cultivar-dependent and gibberellin action involves SLENDER1 but not GAMYB.

    PubMed

    Eastmond, Peter J; Jones, Russell L

    2005-11-01

    Storage oil is a major constituent in the cereal aleurone layer. The aim of this study was to investigate how gibberellin (GA) and abscisic acid (ABA) regulate conversion of oil to sugar in barley aleurone. The activity of the glyoxylate cycle enzyme isocitrate lyase (ICL) was surveyed in eight barley cultivars. Surprisingly, some cultivars do not require GA for the induction of ICL (e.g. Himalaya), whereas some do (e.g. Golden Promise). Furthermore, in Golden Promise, GA also stimulates triacylglycerol breakdown and enhances the net flux of carbon from acetate to sugar. In contrast, ABA strongly represses ICL activity and the flux of carbon from oil to sugar in both Golden Promise and Himalaya. Biolistics using a promoter reporter showed that GA and ABA regulate ICL at the level of transcription. Studies using barley and rice mutants and pharmacological agents show that GA-dependent induction of ICL activity is mediated by SLENDER1 and requires cGMP, but does not involve the transcription factor GAMYB. Gibberellin and ABA therefore act antagonistically to regulate gluconeogenesis in the aleurone layer as well as controlling the production and secretion of hydrolases into the starchy endosperm. We suggest that the variation between different barley cultivars might be a result of selective breeding to alter seed dormancy. PMID:16236157

  5. Suppression of Transglutaminase-2 is Involved in Anti-Inflammatory Actions of Glucosamine in 12-O-Tetradecanoylphorbol-13-Acetate-Induced Skin Inflammation

    PubMed Central

    Cho, Sun A; Lee, Hye Ja; Lee, Eun Ji; Kang, June Hee; Kim, You Lee; Kim, Hyun Ji; Oh, Seung Hyun; Choi, Changsun; Lee, Ho; Kim, Soo Youl

    2012-01-01

    Glucosamine (GS) is well known for the treatment of inflam-mation. However, the mechanism and efficacy of GS for skin inflammation are unclear. The aim of this study was to evaluate the effects and mechanism of GS in the mouse 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema model. TPA-induced ear edema was evoked in ICR or transglutaminase 2 (Tgase-2) (-/-) mice. GS was administered orally (10-100 mg/kg) or topically (0.5-2.0 w/v %) prior to TPA treatment. Orally administered GS at 10 mg/kg showed a 76 or 57% reduction in ear weight or myeloperoxidase, respectively, and a decreased expression of cyclooxy-genase-2 (COX-2), NF-κB and Tgase-2 in TPA-induced ear edema by western blot and immunohistochemistry. Role of Tgase-2 in TPA ear edema is examined using Tgase-2 (-/-) mice and TPA did not induce COX-2 expression in ear of Tgase-2 (-/-) mice. These observations suggested that Tgase-2 is involved in TPA-induced COX-2 expression in the inflamed ear of mice and anti-inflammatory effects of glucosamine is mediated through suppression of Tgase-2 in TPA ear edema. PMID:24009824

  6. Low dose morphine adjuvant therapy for enhanced efficacy of antipsychotic drug action: potential involvement of endogenous morphine in the pathophysiology of schizophrenia.

    PubMed

    Stefano, George B; Králíčková, Milena; Ptacek, Radek; Kuzelova, Hana; Esch, Tobias; Kream, Richard M

    2012-07-01

    Major thematic threads linking extensive preclinical and clinical efforts have established a working mechanistic scheme whereby atypical antipsychotic drugs ameliorate negative DSM IV diagnostic criteria by effecting relatively potent blockade of serotonin (5-HT)(2A) receptors coupled with weaker antagonism of dopamine D(2) receptors in frontal cortical areas. These contentions are more or less supported by in vitro binding experiments employing cloned receptors on cultured cells, although significant functional involvement of 5-HT(2C) receptors has also been proposed. It is interesting that a key statistical analysis indicates a major shift in usage back to typical antipsychotic agents for management of schizophrenia from 1995-2008, whereas off-label usage of atypical antipsychotic agents was markedly increased or expanded for bipolar affective disorder. Importantly, meta-analyses generally did not support efficacy differences between the other atypical antipsychotics compared with the older typical agents. A critical examination of putative functional linkages of morphine and its type-selective mu opioid receptor to higher order cortical regulation of cognitive processes may provide novel insights into human behavioral processes that are severely impaired in schizophrenia spectrum disorders. PMID:22739740

  7. A study of the mechanisms involved in the neurotoxic action of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') on dopamine neurones in mouse brain

    PubMed Central

    Colado, M Isabel; Camarero, Jorge; Mechan, Annis O; Sanchez, Veronica; Esteban, Blanca; Elliott, J Martin; Green, A Richard

    2001-01-01

    Administration of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') to mice produces acute hyperthermia and long-term degeneration of striatal dopamine nerve terminals. Attenuation of the hyperthermia decreases the neurodegeneration. We have investigated the mechanisms involved in producing the neurotoxic loss of striatal dopamine. MDMA produced a dose-dependent loss in striatal dopamine concentration 7 days later with 3 doses of 25 mg kg−1 (3 h apart) producing a 70% loss. Pretreatment 30 min before each MDMA dose with either of the N-methyl-D-aspartate antagonists AR-R15896AR (20, 5, 5 mg kg−1) or MK-801 (0.5 mg kg−1×3) failed to provide neuroprotection. Pretreatment with clomethiazole (50 mg kg−1×3) was similarly ineffective in protecting against MDMA-induced dopamine loss. The free radical trapping compound PBN (150 mg kg−1×3) was neuroprotective, but it proved impossible to separate neuroprotection from a hypothermic effect on body temperature. Pretreatment with the nitric oxide synthase (NOS) inhibitor 7-NI (50 mg kg−1×3) produced neuroprotection, but also significant hypothermia. Two other NOS inhibitors, S-methyl-L-thiocitrulline (10 mg kg−1×3) and AR-R17477AR (5 mg kg−1×3), provided significant neuroprotection and had little effect on MDMA-induced hyperthermia. MDMA (20 mg kg−1) increased 2,3-dihydroxybenzoic acid formation from salicylic acid perfused through a microdialysis tube implanted in the striatum, indicating increased free radical formation. This increase was prevented by AR-R17477AR administration. Since AR-R17477AR was also found to have no radical trapping activity this result suggests that MDMA-induced neurotoxicity results from MDMA or dopamine metabolites producing radicals that combine with NO to form tissue-damaging peroxynitrites. PMID:11739248

  8. Use of Force Preferences and Perceived Effectiveness of Actions Among Crisis Intervention Team (CIT) Police Officers and Non-CIT Officers in an Escalating Psychiatric Crisis Involving a Subject With Schizophrenia

    PubMed Central

    Compton, Michael T.; Demir Neubert, Berivan N.; Broussard, Beth; McGriff, Joanne A.; Morgan, Rhiannon; Oliva, Janet R.

    2011-01-01

    Background: Few studies have examined police officers’ use of force toward individuals with schizophrenia, despite the widely disseminated Crisis Intervention Team (CIT) model of partnership between mental health and law enforcement that seeks to reduce use of force and enhance safety of officers and individuals with mental illnesses. This study tested the hypotheses that CIT-trained officers would select a lower level of force, identify nonphysical actions as more effective, and perceive physical force as less effective in an escalating psychiatric crisis, compared with non–CIT-trained officers. Methods: Police officers (n = 135)—48 CIT trained and 87 non–CIT trained—completed a survey containing 3 scenario-based vignettes depicting an escalating situation involving a subject with psychosis. Data were analyzed using repeated-measures analyses of variance. Results: Officers escalated their preferred actions across the scenarios. A significant scenario by group interaction indicated that CIT-trained officers chose less escalation (ie, opting for less force at the third scenario) than non–CIT-trained officers. Officers reported decreasing perceived effectiveness of nonphysical action across the 3 scenarios. A significant scenario by group interaction indicated that CIT-trained officers reported a lesser decline in perceived effectiveness of nonphysical actions at the third scenario. CIT-trained officers consistently endorsed lower perceived effectiveness of physical force. Conclusions: Efforts are needed to reduce use of force toward individuals with psychotic disorders. These findings suggest that CIT may be an effective approach. In addition to clinical and programmatic implications, such findings demonstrate a role for clinicians, advocates, and schizophrenia researchers in promoting social justice through partnerships with diverse social sectors. PMID:19933714

  9. Stage I/II follicular lymphoma: spread of bcl-2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy.

    PubMed

    Pulsoni, Alessandro; Starza, Irene Della; Frattarelli, Natalia; Ghia, Emanuela; Carlotti, Emanuela; Cavalieri, Elena; Matturro, Angela; Tempera, Settimio; Rambaldi, Alessandro; Foà, Robin

    2007-05-01

    Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl-2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66.6%). After treatment, in 9/15 Bcl-2/IgH positive evaluable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 43.5 months (range 11-70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl-2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl-2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR. PMID:17408460

  10. A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in protective effect of the proton pump inhibitor pantoprazole against indomethacin-induced gastric damage in rats

    PubMed Central

    2012-01-01

    Background Proton pump is an integral membrane protein that is ubiquitous ATP binding cassette (ABC) involved in many transport processes in all living organisms, among which a specialized form of pump, so called p-type proton pump, exists in the parietal cells of stomach. Though proton pump inhibitors (PPIs) are frequently prescribed to prevent nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage, the acid suppressive actions do not suffice to explain. Methods In order to document the effects of pantoprazole, one of PPIs, on the NSAIDs-induced gastric damage, in vitro and in vivo studies were performed. Immunocytochemistry, Western blot analysis, electrophoretic mobility shift assay and RT-PCR were conducted to evaluate the induction of heme oxygenase-1 (HO-1) through Nrf2 activation in normal gastric mucosal RGM-1 cells or in vivo stomach tissues from rats treated with indomethacin and/or pantoprazole. Results Pantoprazole activated Nrf2 through inactivation of Keap1, after which the expression of HO-1 was significantly increased in a dose-dependent manner in RGM-1 cells. Increased ARE-DNA binding activity was observed maximally at 1 h with 300 μM of pantoprazole. The expression of HO-1 induced by pantoprazole was significantly associated with the increased in vitro tube formation (P < 0.05) and angiogenic factors including VEGF, bFGF, and HIF-1α. Indomethacin markedly increased the expressions of TNF-α, IL-1ß, IL-8, NOX-1, ICAM-1 and VCAM, whereas pantoprazole significantly decreased the expressions of indomethacin-induced these inflammatory mediators in accord with pantoprazole-induced HO-1 (P < 0.05) as documented with HO-1 inhibitor. In vivo model of indomethacin-induced gastric damage could validate in vitro-drawn results that pantoprazole remarkably protected against indomethacin-induced gastric damage, in which zinc protoporphyrin (5 mg/kg, ip) significantly abolished the protective efficacy of pantoprazole. Conclusion These results

  11. Androgen action.

    PubMed

    Werner, Ralf; Holterhus, Paul-Martin

    2014-01-01

    Androgens are important for male sex development and physiology. Their actions are mediated by the androgen receptor (AR), a ligand-dependent nuclear transcription factor. The activity of the AR is controlled at multiple stages due to ligand binding and induced structural changes assisted by the foldosome, compartmentalization, recruitment of coregulators, posttranslational modifications and chromatin remodeling, leading to subsequent transcription of androgen-responsive target genes. Beside these short-term androgen actions, there is phenomenological and experimental evidence of long-term androgen programming in mammals and in the human during sensitive programming time windows, both pre- and postnatally. At the molecular level, research into androgen insensitivity syndrome has unmasked androgen programming at the transcriptome level, in genital fibroblasts and peripheral blood mononuclear cells, and at the epigenome level. Androgens are crucial for male sex development and physiology during embryogenesis, at puberty and in adult life. Testosterone and its more potent metabolite, dihydrotestosterone, which is converted from testosterone within the target cell by 5α-reductase II, are the main androgens involved in male sex differentiation. Androgen action is mediated by a single AR. The AR belongs to the nuclear receptor 3 group C, composed of the glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), progesterone receptor (NR3C3) and AR (NR3C4), and acts as a ligand-dependent transcription factor. PMID:25247642

  12. Renormalized action improvements

    SciTech Connect

    Zachos, C.

    1984-01-01

    Finite lattice spacing artifacts are suppressed on the renormalized actions. The renormalized action trajectories of SU(N) lattice gauge theories are considered from the standpoint of the Migdal-Kadanoff approximation. The minor renormalized trajectories which involve representations invariant under the center are discussed and quantified. 17 references.

  13. Handbook for Ecology Action.

    ERIC Educational Resources Information Center

    Eber, Ronald

    This handbook has been compiled to aid concerned individuals and ecology groups more adequately define their goals, initiate good programs, and take effective action. It examines the ways a group of working individuals can become involved in action programs for ecological change. Part 1 deals with organization, preliminary organizing, structuring,…

  14. The generalized anomeric effect in the 1,3-thiazolidines: Evidence for both sulphur and nitrogen as electron donors. Crystal structures of various N-acylthiazolidines including mercury(II) complexes. Possible relevance to penicillin action

    NASA Astrophysics Data System (ADS)

    Chandrasekhar, Sosale; Chopra, Deepak; Gopalaiah, Kovuru; Guru Row, Tayur N.

    2007-06-01

    Evidence for the generalized anomeric effect (GAE) in the N-acyl-1,3-thiazolidines, an important structural motif in the penicillins, was sought in the crystal structures of N-(4-nitrobenzoyl)-1,3-thiazolidine and its (2:1) complex with mercuric chloride, N-acetyl-2-phenyl-1,3-thiazolidine, and the (2:1) complex of N-benzoyl-1,3-thiazolidine with mercuric bromide. An inverse relationship was generally observed between the C2- N and C2- S bond lengths of the thiazolidine ring, supporting the existence of the GAE. (Maximal bond length changes were ˜0.04 Å for C2- N3, S1- C2, and ˜0.08 Å for N3- C6.) Comparison with N-acylpyrrolidines and tetrahydrothiophenes indicates that both the nitrogen-to-sulphur and sulphur-to-nitrogen GAE's operate simultaneously in the 1,3-thiazolidines, the former being dominant. (This is analogous to the normal and exo-anomeric effects in pyranoses, and also leads to an interesting application of Baldwin's rules.) The nitrogen-to-sulphur GAE is generally enhanced in the mercury(II) complexes (presumably via coordination at the sulphur); a 'competition' between the GAE and the amide resonance of the N-acyl moiety is apparent. There is evidence for a 'push-pull' charge transfer between the thiazolidine moieties in the mercury(II) complexes, and for a 'back-donation' of charge from the bromine atoms to the thiazolidine moieties in the HgBr 2 complex. (The sulphur atom appears to be sp 2 hybridised in the mercury(II) complexes, possibly for stereoelectronic reasons.) These results are apparently relevant to the mode of action of the penicillins.

  15. A neural network model of causative actions.

    PubMed

    Lee-Hand, Jeremy; Knott, Alistair

    2015-01-01

    A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g., Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umiltà et al., 2008; Hommel, 2013). In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John smashes a cup, he brings about the event of the cup smashing. Other actions do not bring about such effects. For instance, if John grabs a cup, this action does not cause the cup to "do" anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organized into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognizes arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the "causative actions" circuit in our model can be identified with a motor pathway reported in other work, specializing in "functional" actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013). PMID:26175685

  16. Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes

    PubMed Central

    Tatone, Carla; Carbone, Maria Cristina

    2006-01-01

    Background Mammalian sperm-oocyte interaction at fertilization involves several combined interactions between integrins on the oocyte and integrin ligands (disintegrins) on the sperm. Recent research has indicated the ability of peptides containing the RGD sequence that characterized several sperm disintegrins, to induce intracellular Ca2+ transients and to initiate parthenogenetic development in amphibian and bovine oocytes. In the present study, we investigate the hypothesis that an integrin-associated signalling may participate in oocyte activation signalling by determining the ability of a cyclic RGD-containing peptide to stimulate the activation of protein kinase C (PKC) and the exocytosis of cortical granules in mouse oocytes. Methods An In-Vitro-Fertilization assay (IVF) was carried in order to test the condition under which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val), was able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage. PKC activity was determined by means of an assay based on the ability of cell lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of cortical granules was evaluated by measuring density in the oocyte cortex of cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the experiments, effects of a control peptide containing a non RGD sequence, cyclo(Arg-Ala-Asp-D-Phe-Val), were evaluated. Results The IVF assay revealed that the fusion rate declined significantly when insemination was carried out in the presence of cyclic RGD peptide at concentrations > or = 250 microM (P < 0.05, Student-Newman-Keuls Method). When the peptide was applied to the oocytes at these concentrations, a dose-dependent increase of PKC activity was observed, in association with a loss of cortical granules ranging from 38+/-2.5 % to 52+/-5.4 %. Evaluation of meiotic status revealed that cyclic RGD peptide was ineffective in inducing meiosis resumption under conditions used in the

  17. Ground-water, surface-water, and bottom-sediment contamination in the O-field area, Aberdeen Proving Ground, Maryland, and the possible effects of selected remedial actions on ground water

    USGS Publications Warehouse

    Vroblesky, Don A.; Lorah, Michelle M.; Oliveros, James P.

    1995-01-01

    Disposal of munitions and chemical-warfare substances has introduced inorganic and organic contaminants to the ground water, surface water, and bottom sediment at O-Field, in the Edgewood area of Aberdeen Proving Ground, Maryland. Contaminants include chloride, arsenic, transition metals, chlorinated aliphatic hydrocarbons, aromatic compounds, and organosulfur and organophosphorus compounds. The hydrologic effects of several remedial actions were estimated by use of a ground-water-flow model. The remedial actions examined were an impermeable covering, encapsulation, subsurface barriers, a ground-water drain, pumping of wells to manage water levels or to remove contaminated ground water for treatment, and no action.

  18. Intentional Action and Action Slips.

    ERIC Educational Resources Information Center

    Heckhausen, Heinz; Beckmann, Jurgen

    1990-01-01

    An explanation of action slips is offered that examines controlled actions in the context of an intentional behavior theory. Actions are considered guided by mentally represented intentions, subdivided into goal intentions and contingent instrumental intentions. Action slips are categorized according to problem areas in the enactment of goal…

  19. A neural network model of causative actions

    PubMed Central

    Lee-Hand, Jeremy; Knott, Alistair

    2015-01-01

    A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g., Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umiltà et al., 2008; Hommel, 2013). In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John smashes a cup, he brings about the event of the cup smashing. Other actions do not bring about such effects. For instance, if John grabs a cup, this action does not cause the cup to “do” anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organized into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognizes arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the “causative actions” circuit in our model can be identified with a motor pathway reported in other work, specializing in “functional” actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013). PMID:26175685

  20. Motor Execution Affects Action Prediction

    ERIC Educational Resources Information Center

    Springer, Anne; Brandstadter, Simone; Liepelt, Roman; Birngruber, Teresa; Giese, Martin; Mechsner, Franz; Prinz, Wolfgang

    2011-01-01

    Previous studies provided evidence of the claim that the prediction of occluded action involves real-time simulation. We report two experiments that aimed to study how real-time simulation is affected by simultaneous action execution under conditions of full, partial or no overlap between observed and executed actions. This overlap was analysed by…

  1. Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

    PubMed

    Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

    2016-06-01

    The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

  2. Dosing time-dependent actions of psychostimulants.

    PubMed

    Manev, H; Uz, T

    2009-01-01

    The concept of the dosing time-dependent (DTD) actions of drugs has been used to describe the effects of diurnal rhythms on pharmacological responsiveness. Notwithstanding the importance of diurnal variability in drug pharmacokinetics and bioavailability, it appears that in the central nervous system (CNS), the DTD actions of psychotropic drugs involve diurnal changes in the CNS-specific expression of genes encoding for psychotropic drug targets and transcription factors known as clock genes. In this review, we focused our discussion on the DTD effects of the psychostimulants cocaine and amphetamines. Both cocaine and amphetamines produce differential lasting behavioral alterations, that is, locomotor sensitization, depending on the time of the day they are administered. This exemplifies a DTD action of these drugs. The DTD effects of these psychostimulants correlate with diurnal changes in the system of transcription factors termed clock genes, for example, Period 1, and with changes in the availability of certain subtypes of dopamine receptors, for example, D2 and D3. Diurnal synthesis and release of the pineal hormone melatonin influence the DTD behavioral actions of cocaine and amphetamines. The molecular mechanism of melatonin's effects on the responsiveness of CNS to psychostimulants appears to involve melatonin receptors and clock genes. It is proposed that the DTD characteristics of psychostimulant action and the contributions of the melatonergic system may have clinical implications that include treatments for the attention deficit hyperactivity disorder and possibly neurotoxicity/neuroprotection. PMID:19897073

  3. Environmental Action.

    ERIC Educational Resources Information Center

    Lott, Jesse; Allen, Rodney F.

    This booklet, a general guide to citizen eco-action, discusses a plan of action on community environmental problems. It offers factors to be considered in any community eco-action situation, but it is not a rigid set of rules. An overview identifies seven key ideas of environmental issues, including the universal participation of all humans in the…

  4. Conscious Control over Action

    PubMed Central

    Shepherd, Joshua

    2015-01-01

    The extensive involvement of nonconscious processes in human behaviour has led some to suggest that consciousness is much less important for the control of action than we might think. In this article I push against this trend, developing an understanding of conscious control that is sensitive to our best models of overt (that is, bodily) action control. Further, I assess the cogency of various zombie challenges—challenges that seek to demote the importance of conscious control for human agency. I argue that though nonconscious contributions to action control are evidently robust, these challenges are overblown. PMID:26113753

  5. Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

    PubMed Central

    Omotayo, T.I.; Akinyemi, G.S.; Omololu, P.A.; Ajayi, B.O.; Akindahunsi, A.A.; Rocha, J.B.T.; Kade, I.J.

    2014-01-01

    The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA) inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump. PMID:25618580

  6. Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity.

    PubMed

    Omotayo, T I; Akinyemi, G S; Omololu, P A; Ajayi, B O; Akindahunsi, A A; Rocha, J B T; Kade, I J

    2015-01-01

    The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe(2+)-mediated in vitro oxidative stress model. The results show that Fe(2+) inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe(2+) inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA) inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe(2+) may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe(2+) and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump. PMID:25618580

  7. Stochastic and nonstochastic post-transcriptional silencing of chitinase and beta-1,3-glucanase genes involves increased RNA turnover-possible role for ribosome-independent RNA degradation.

    PubMed Central

    Holtorf, H; Schöb, H; Kunz, C; Waldvogel, R; Meins, F

    1999-01-01

    Stochastic and nonstochastic post-transcriptional gene silencing (PTGS) in Nicotiana sylvestris plants carrying tobacco class I chitinase (CHN) and beta-1,3-glucanase transgenes differs in incidence, stability, and pattern of expression. Measurements with inhibitors of RNA synthesis (cordycepin, actinomycin D, and alpha-amanitin) showed that both forms of PTGS are associated with increased sequence-specific degradation of transcripts, suggesting that increased RNA turnover may be a general feature of PTGS. The protein synthesis inhibitors cycloheximide and verrucarin A did not inhibit degradation of CHN RNA targeted for PTGS, confirming that PTGS-related RNA degradation does not depend on ongoing protein synthesis. Because verrucarin A, unlike cycloheximide, dissociates mRNA from ribosomes, our results also suggest that ribosome-associated RNA degradation pathways may not be involved in CHN PTGS. PMID:10072405

  8. Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.

    PubMed

    Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J; Aramaki, Hironori

    2014-12-01

    We recently reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ(9)-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ(9)-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ(9)-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ(9)-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ(9)-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ(9)-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ(9)-THC up-regulation of FA2H in MDA-MB-231 cells. PMID:25291031

  9. Δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

    PubMed Central

    Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J.; Aramaki, Hironori

    2014-01-01

    We recently reported that Δ9-tetrahydrocannabinol (Δ9-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2 hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ9-THC treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA MB 231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ9-THC mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ9 THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ9-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ9-THC induced up regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ9 THC up-regulation of FA2H in MDA-MB-231 cells. PMID:25291031

  10. [Addictions and action systems].

    PubMed

    Loonis, E; Apter, M J

    2000-01-01

    Generalizing from some previous analyses of addiction, and introducing the concept of an action system which governs all actions which are focussed on what Brown (1988) calls "hedonic management", we argue that addictions of every kind involve an action system that displays high salience, low variety and low vicariance. Addictions also involve what Apter (1982) calls the "paratelic state". A study was carried out comparing 31 drug addicts with 29 control subjects in terms of action system variables. To measure these variables, we constructed a new instrument, the Activity-System Drawing Test, and also used the Telic Dominance Scale to measure frequency of paratelic states. Dysphoria was measured by means of the BATE (anxiety), IDA-13 (depression), SEI (self-esteem), and TAS-20 (alexithymia) instruments. Strongly significant differences were found between groups for both action system variables and dysphoria, and there were also strong correlations between both groups of variables. This supports the idea that addictions emerge from systemic properties of the action system. PMID:10858918

  11. Involvement of Outer Membrane Protein TolC, a Possible Member of the mar-sox Regulon, in Maintenance and Improvement of Organic Solvent Tolerance of Escherichia coli K-12

    PubMed Central

    Aono, Rikizo; Tsukagoshi, Norihiko; Yamamoto, Mami

    1998-01-01

    Escherichia coli mutants with improved organic solvent tolerance levels showed high levels of outer membrane protein TolC and inner membrane protein AcrA. The TolC level was regulated positively by MarA, Rob, or SoxS. A possible mar-rob-sox box sequence was found upstream of the tolC gene. These findings suggest that tolC is a member of the mar-sox regulon responsive to stress conditions. When a defective tolC gene was transferred to n-hexane- or cyclohexane-tolerant strains by P1 transduction, the organic solvent tolerance level was lowered dramatically to the decane-tolerant and nonane-sensitive level. The tolerance level was restored by transformation of the transductants with a wild-type tolC gene. Therefore, it is evident that TolC is essential for E. coli to maintain organic solvent tolerance. PMID:9473050

  12. Action Learning.

    ERIC Educational Resources Information Center

    1996

    These four papers were presented at a symposium on action learning moderated by Lex Dilworth at the 1996 conference of the Academy of Human Resource Development. "Developing an Infrastructure for Individual and Organizational Change: Transfer of Learning from an Action Reflection Learning (ARL) Program" (ARL Inquiry) reports findings from a study…

  13. 32 CFR 651.13 - Classified actions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Classified actions. 651.13 Section 651.13... § 651.13 Classified actions. (a) For proposed actions and NEPA analyses involving classified information... proposed action. (c) When classified information can be reasonably separated from other information and...

  14. From Awareness to Action

    ERIC Educational Resources Information Center

    Micklos, John, Jr.

    2012-01-01

    What inspires young people to become activists? Events such as wars or regime changes obviously raise high emotions. But some choose to get involved because they saw a need and felt compelled to take action. Young Americans have a long track record as activists. Among other things, they played a key role in the civil rights movement of the 1950s…

  15. Instructional Rounds in Action

    ERIC Educational Resources Information Center

    Roberts, John E.

    2012-01-01

    "Instructional Rounds in Action" is an invaluable guide for those involved in implementing instructional rounds as the foundation and framework for systemic improvement in schools. Over the past few years, districts across the United States, Canada, and Australia have begun implementing "instructional rounds," a set of ideas and practices for…

  16. Time-course changes in muscle protein degradation in heat-stressed chickens: Possible involvement of corticosterone and mitochondrial reactive oxygen species generation in induction of the ubiquitin-proteasome system.

    PubMed

    Furukawa, Kyohei; Kikusato, Motoi; Kamizono, Tomomi; Toyomizu, Masaaki

    2016-03-01

    Heat stress (HS) induces muscle protein degradation as well as production of mitochondrial reactive oxygen species (ROS). In the present study, to improve our understanding of how protein degradation is induced by HS treatment in birds, a time course analysis of changes in the circulating levels of glucocorticoid and N(τ)-methylhistidine, muscle proteolysis-related gene expression, and mitochondrial ROS generation, was conducted. At 25days of age, chickens were exposed to HS conditions (33°C) for 0, 0.5, 1 or 3days. While no alteration in plasma N(τ)-methylhistidine concentration relative to that of the control group was observed in the 0.5day HS group, the concentration was significantly higher in the 3-d HS treatment group. Plasma corticosterone concentrations increased in response to 0.5-d HS treatment, but subsequently returned to near-normal values. HS treatment for 0.5days did not change the levels of μ-calpain, cathepsin B, or proteasome C2 subunit mRNA, but increased the levels of mRNA encoding atrogin-1 (P<0.05) and its transcription factor, forkhead box O3 (P=0.09). Under these hyperthermic conditions, mitochondrial superoxide production was significantly increased than that of thermoneutral control. Here, we show that HS-induced muscle protein degradation may be due to the activation of ubiquitination by atrogin-1, and that this process may involve mitochondrial ROS production as well as corticosterone secretion. PMID:26883687

  17. Garcinone D, a natural xanthone promotes C17.2 neural stem cell proliferation: Possible involvement of STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway.

    PubMed

    Yang, Xiaohong; Wang, Shengnan; Ouyang, Ying; Tu, Yaling; Liu, Anmin; Tian, Yinghong; He, Mingliang; Pi, Rongbiao

    2016-07-28

    Garcinia mangostana L. (Mangosteen) has been used to treat various pathological conditions, including inflammation and urinary tract infections. Here, we observed that garcinone D, a natural xanthone from mangosteen, promoted the proliferation of C17.2 neural progenitor cells and also resulted in a larger percentage of cells in S phase compared with the control group. Moreover, garcinone D increased the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and Cyclin D1 in concentration- and time- dependent manners. Garcinone D also increased the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in concentration- and time- dependent manners, and inhibiting Nrf2 activation by brusatol could partly reverse garcinone D-induced C17.2 cell proliferation. Taken together, it is the first time to show that garcinone D promotes the proliferation of C17.2 neural stem cells, which may involve the STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway. It would provide new inspiration to develop garcinone D as a lead compound to promote the proliferation of endogenous neural stem cells (NSCs). PMID:27177723

  18. A distributed network critical for selecting among tool-directed actions.

    PubMed

    Watson, Christine E; Buxbaum, Laurel J

    2015-04-01

    Tools pose a challenge to the need to select actions appropriate for task goals and environmental constraints. For many tools (e.g., calculator), actions for "using" and "grasping-to-move" conflict with each other and may compete during selection. To date, little is known about the mechanisms that enable selection between possible tool actions or their neural substrates. The study of patients with chronic left hemisphere stroke, many of whom are deficient in tool-use action (apraxic), provides an opportunity to elucidate these issues. Here, 31 such patients pantomimed or recognized tool use actions for "conflict" and "non-conflict" tools. Voxel-based lesion-symptom mapping (VLSM), lesion subtraction, and tractographic overlap analyses were used to determine brain regions necessary for selecting among tool-directed actions. Lesions to posterior middle temporal gyrus (pMTG) and anterior intraparietal sulcus (aIPS) tended to impair production of use actions similarly for both conflict and non-conflict tools. By contrast, lesions to the supramarginal gyrus (SMG), inferior frontal gyrus (IFG)/anterior insula, and superior longitudinal fasciculus (SLF) specifically impaired production of use actions for conflict tools. Patients' errors on conflict tools suggested inappropriate selection of grasping actions and difficulty selecting single actions. Use/grasp conflict had no effect on action recognition. We suggest that the SMG/SLF/IFG pathway implements biased competition between possible tool actions, while aIPS and pMTG compute the structure-based and skilled use actions, respectively, that constitute input to this competitive process. This is the first study to demonstrate a reliable link between a characteristic of single tools (i.e., their association with different use and grasp actions) and action selection difficulties. Additionally, the data allow us to posit an SMG-involved subtype of apraxia characterized by an inability to resolve action competition. PMID

  19. A Distributed Network Critical for Selecting Among Tool-Directed Actions

    PubMed Central

    Watson, Christine E.; Buxbaum, Laurel J.

    2015-01-01

    Tools pose a challenge to the need to select actions appropriate for task goals and environmental constraints. For many tools (e.g., calculator), actions for “using” and “grasping-to-move” conflict with each other and may compete during selection. To date, little is known about the mechanisms that enable selection between possible tool actions or their neural substrates. The study of patients with chronic left hemisphere stroke, many of whom are deficient in tool-use action (apraxic), provides an opportunity to elucidate these issues. Here, 31 such patients pantomimed or recognized tool use actions for “conflict” and “non-conflict” tools. Voxel-based lesion-symptom mapping, lesion subtraction, and tractographic overlap analyses were used to determine brain regions necessary for selecting among tool-directed actions. Lesions to posterior middle temporal gyrus (pMTG) and anterior intraparietal sulcus (aIPS) tended to impair production of use actions similarly for both conflict and non-conflict tools. By contrast, lesions to the supramarginal gyrus (SMG), inferior frontal gyrus (IFG)/anterior insula, and superior longitudinal fasciculus (SLF) specifically impaired production of use actions for conflict tools. Patients' errors on conflict tools suggested inappropriate selection of grasping actions and difficulty selecting single actions. Use/grasp conflict had no effect on action recognition. We suggest that the SMG/SLF/IFG pathway implements biased competition between possible tool actions, while aIPS and pMTG compute the structure-based and skilled use actions, respectively, that constitute input to this competitive process. This is the first study to demonstrate a reliable link between a characteristic of single tools (i.e., their association with different use and grasp actions) and action selection difficulties. Additionally, the data allow us to posit a SMG-involved subtype of apraxia characterized by an inability to resolve action competition

  20. Involvement of peroxisome proliferator-activated receptor β/δ (PPAR β/δ) in BDNF signaling during aging and in Alzheimer disease: possible role of 4-hydroxynonenal (4-HNE).

    PubMed

    Benedetti, Elisabetta; D'Angelo, Barbara; Cristiano, Loredana; Di Giacomo, Erica; Fanelli, Francesca; Moreno, Sandra; Cecconi, Francesco; Fidoamore, Alessia; Antonosante, Andrea; Falcone, Roberta; Ippoliti, Rodolfo; Giordano, Antonio; Cimini, Annamaria

    2014-01-01

    Aging and many neurological disorders, such as AD, are linked to oxidative stress, which is considered the common effector of the cascade of degenerative events. In this phenomenon, reactive oxygen species play a fundamental role in the oxidative decomposition of polyunsaturated fatty acids, resulting in the formation of a complex mixture of aldehydic end products, such as malondialdehyde, 4-hydroxynonenal, and other alkenals. Interestingly, 4-HNE has been indicated as an intracellular agonist of peroxisome proliferator-activated receptor β/δ. In this study, we examined, at early and advanced AD stages (3, 9, and 18 months), the pattern of 4-HNE and its catabolic enzyme glutathione S-transferase P1 in relation to the expression of PPARβ/δ, BDNF signaling, as mRNA and protein, as well as on their pathological forms (i.e., precursors or truncated forms). The data obtained indicate a novel detrimental age-dependent role of PPAR β/δ in AD by increasing pro-BDNF and decreasing BDNF/TrkB survival pathways, thus pointing toward the possibility that a specific PPARβ/δ antagonist may be used to counteract the disease progression. PMID:24621497

  1. Suppression of development of anti-nuclear antibody and glomerulonephritis in NZB x NZWF1 mice by persistent infection with lactic dehydrogenase virus: possible involvement of superoxide anion as a progressive effector.

    PubMed Central

    Hayashi, T.; Noguchi, Y.; Kameyama, Y.

    1993-01-01

    The development of anti-nuclear antibody (ANA) and glomerulonephritis (GN) in autoimmune NZB x NZWF1 mice was suppressed by persistent lactic dehydrogenase virus (LDV) infection. This observation was used to study a possible pathogenetic role for the toxic oxygen radical, superoxide anion (O2-), in the progression of ANA and GN. Compared to macrophages from NZB x NZWF1 mice with LDV infection, macrophages from uninfected NZB x NZWF1 mice exhibited an age-related and drastic increase in O2- production in association with the development of the ANA and GN (representing the late stage of disease). NZB x NZWF1 mice with or without LDV infection were then given the O2- scavenger superoxide dismutase (SOD) during the late stage of the disease. Treatment of uninfected NZB x NZWF1 mice with SOD (10,000 units/mouse/day for 3 weeks) protected animals from the development of ANA and GN. SOD treatment also suppressed the development of the lesions in NZB x NZWF1 mice with LDV infection. Our findings suggest that O2- may, at least in part, contribute to the development of ANA and GN in the late stage of disease, and that decreased O2- production in NZB x NZWF1 mice with LDV infection may be responsible for the suppression of the development of ANA and GN in the late stage of the disease. Images Figure 7 Figure 9 PMID:8292553

  2. Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome.

    PubMed

    Shao, Anwen; Wu, Haijian; Hong, Yuan; Tu, Sheng; Sun, Xuejun; Wu, Qun; Zhao, Qiong; Zhang, Jianmin; Sheng, Jifang

    2016-07-01

    Early brain injury (EBI), highlighted with inflammation and apoptosis, occurring within 72 h after subarachnoid hemorrhage (SAH), is associated with the prognosis of SAH. Recent studies have revealed that hydrogen-rich saline (HS) exerted multiple neuroprotective properties in many neurological diseases including SAH, involved to anti-oxidative and anti-apoptotic effect. We have previously reported that HS could attenuate neuronal apoptosis as well as vasospasm. However, the underlying mechanism of HS on inflammation in SAH-induced EBI remains unclear. In this study, we explored the influence of HS on nuclear factor-κB (NF-κB) pathway and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome at early stage after SAH, by injecting HS intraperitoneally to SAH rats. One hundred and twenty-nine SD rats were randomly divided into four groups: sham group, SAH group, SAH+vehicle group, and SAH+HS group. SAH model was conducted using endovascular perforation method; all rats were sacrificed at 24 h after SAH. Protein level of pIκBα, cytosolic and nuclear p65, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, interleukin-1β (IL-1β), and cleaved caspase-3 were measured by western blot. mRNA level of IL-1β, interleukin-6 (IL-6), tumor necrosis factor-c (TNF-α) were evaluated by RT-PCR. Cellular injury and death was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Nissl staining, respectively. Our results showed that pIκBα, nuclear p65, NLRP3, ASC, caspase-1, IL-1β, cleaved caspase-3 proteins, as well as the mRNA of IL-1β, IL-6, and TNF-ɑ increased at 24 h after SAH, while cytosolic p65 decreased. TUNEL and Nissl staining presented severe cellular injury at 24 h post-SAH. However, after HS administration, the changes mentioned above were reversed. In conclusion, HS may inhibit inflammation in EBI and improve

  3. A Comprehensive Profile of ChIP-Seq-Based Olig2 Target Genes in Motor Neuron Progenitor Cells Suggests the Possible Involvement of Olig2 in the Pathogenesis of Amyotrophic Lateral Sclerosis

    PubMed Central

    Satoh, Jun-ichi; Asahina, Naohiro; Kitano, Shouta; Kino, Yoshihiro

    2015-01-01

    BACKGROUND Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease that primarily affects motor neurons in the cerebral cortex and the spinal cord. Recent evidence indicates that dysfunction of oligodendrocytes is implicated in the pathogenesis of ALS. The basic helix–loop–helix (bHLH) transcription factor Olig2 plays a pivotal role in the development of both motor neurons and oligodendrocytes in the progenitor of motor neuron (pMN) domain of the spinal cord, supporting evidence for the shared motor neuron/oligodendrocyte lineage. However, a comprehensive profile of Olig2 target genes in pMNs and oligodendrocyte progenitor cells (OPCs) with relevance to the pathogenesis of ALS remains to be characterized. METHODS By analyzing the ChIP-Seq datasets